--- _id: '9549' abstract: - lang: eng text: 'AMPA receptors (AMPARs) mediate the majority of excitatory transmission in the brain and enable the synaptic plasticity that underlies learning1. A diverse array of AMPAR signalling complexes are established by receptor auxiliary subunits, which associate with the AMPAR in various combinations to modulate trafficking, gating and synaptic strength2. However, their mechanisms of action are poorly understood. Here we determine cryo-electron microscopy structures of the heteromeric GluA1–GluA2 receptor assembled with both TARP-γ8 and CNIH2, the predominant AMPAR complex in the forebrain, in both resting and active states. Two TARP-γ8 and two CNIH2 subunits insert at distinct sites beneath the ligand-binding domains of the receptor, with site-specific lipids shaping each interaction and affecting the gating regulation of the AMPARs. Activation of the receptor leads to asymmetry between GluA1 and GluA2 along the ion conduction path and an outward expansion of the channel triggers counter-rotations of both auxiliary subunit pairs, promoting the active-state conformation. In addition, both TARP-γ8 and CNIH2 pivot towards the pore exit upon activation, extending their reach for cytoplasmic receptor elements. CNIH2 achieves this through its uniquely extended M2 helix, which has transformed this endoplasmic reticulum-export factor into a powerful AMPAR modulator that is capable of providing hippocampal pyramidal neurons with their integrative synaptic properties. ' acknowledgement: We thank members of the Greger laboratory, B. Herguedas, J. Krieger and J.-N. Dohrke for comments on the manuscript; J. Krieger and J.-N. Dohrke for discussion, J. Krieger for help with the normal mode analysis, B. Köhegyi for help with cryo-EM imaging, V. Chang and K. Suzuki for helping to generate the CNIH2-1D4-HA stable cell line, M. Carvalho for assistance at early stages of this project, the LMB scientific computing and the cryo-EM facility for support, P. Emsley for help with model building, T. Nakane for helpful comments with RELION 3.1 and R. Warshamanage for helping with EMDA cryo-EM-map processing. We acknowledge the Diamond Light Source for access and support of the Cryo-EM facilities at the UK national electron bio10 imaging centre (eBIC), proposal EM17434, funded by the Wellcome Trust, MRC and BBSRC. This work was supported by grants from the Medical Research Council, as part of United Kingdom Research and Innovation (also known as UK Research and Innovation) (MC_U105174197) and BBSRC (BB/N002113/1) to I.H.G. article_processing_charge: No article_type: original author: - first_name: Danyang full_name: Zhang, Danyang last_name: Zhang - first_name: Jake full_name: Watson, Jake id: 63836096-4690-11EA-BD4E-32803DDC885E last_name: Watson orcid: 0000-0002-8698-3823 - first_name: Peter M. full_name: Matthews, Peter M. last_name: Matthews - first_name: Ondrej full_name: Cais, Ondrej last_name: Cais - first_name: Ingo H. full_name: Greger, Ingo H. last_name: Greger citation: ama: Zhang D, Watson J, Matthews PM, Cais O, Greger IH. Gating and modulation of a hetero-octameric AMPA glutamate receptor. Nature. 2021;594:454-458. doi:10.1038/s41586-021-03613-0 apa: Zhang, D., Watson, J., Matthews, P. M., Cais, O., & Greger, I. H. (2021). Gating and modulation of a hetero-octameric AMPA glutamate receptor. Nature. Springer Nature. https://doi.org/10.1038/s41586-021-03613-0 chicago: Zhang, Danyang, Jake Watson, Peter M. Matthews, Ondrej Cais, and Ingo H. Greger. “Gating and Modulation of a Hetero-Octameric AMPA Glutamate Receptor.” Nature. Springer Nature, 2021. https://doi.org/10.1038/s41586-021-03613-0. ieee: D. Zhang, J. Watson, P. M. Matthews, O. Cais, and I. H. Greger, “Gating and modulation of a hetero-octameric AMPA glutamate receptor,” Nature, vol. 594. Springer Nature, pp. 454–458, 2021. ista: Zhang D, Watson J, Matthews PM, Cais O, Greger IH. 2021. Gating and modulation of a hetero-octameric AMPA glutamate receptor. Nature. 594, 454–458. mla: Zhang, Danyang, et al. “Gating and Modulation of a Hetero-Octameric AMPA Glutamate Receptor.” Nature, vol. 594, Springer Nature, 2021, pp. 454–58, doi:10.1038/s41586-021-03613-0. short: D. Zhang, J. Watson, P.M. Matthews, O. Cais, I.H. Greger, Nature 594 (2021) 454–458. date_created: 2021-06-13T22:01:33Z date_published: 2021-06-02T00:00:00Z date_updated: 2023-08-08T13:59:51Z day: '02' department: - _id: PeJo doi: 10.1038/s41586-021-03613-0 external_id: isi: - '000657238100003' pmid: - '34079129' intvolume: ' 594' isi: 1 language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1038/s41586-021-03613-0 month: '06' oa: 1 oa_version: Published Version page: 454-458 pmid: 1 publication: Nature publication_identifier: eissn: - 1476-4687 issn: - 0028-0836 publication_status: published publisher: Springer Nature quality_controlled: '1' scopus_import: '1' status: public title: Gating and modulation of a hetero-octameric AMPA glutamate receptor type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 594 year: '2021' ... --- _id: '9778' abstract: - lang: eng text: The hippocampal mossy fiber synapse is a key synapse of the trisynaptic circuit. Post-tetanic potentiation (PTP) is the most powerful form of plasticity at this synaptic connection. It is widely believed that mossy fiber PTP is an entirely presynaptic phenomenon, implying that PTP induction is input-specific, and requires neither activity of multiple inputs nor stimulation of postsynaptic neurons. To directly test cooperativity and associativity, we made paired recordings between single mossy fiber terminals and postsynaptic CA3 pyramidal neurons in rat brain slices. By stimulating non-overlapping mossy fiber inputs converging onto single CA3 neurons, we confirm that PTP is input-specific and non-cooperative. Unexpectedly, mossy fiber PTP exhibits anti-associative induction properties. EPSCs show only minimal PTP after combined pre- and postsynaptic high-frequency stimulation with intact postsynaptic Ca2+ signaling, but marked PTP in the absence of postsynaptic spiking and after suppression of postsynaptic Ca2+ signaling (10 mM EGTA). PTP is largely recovered by inhibitors of voltage-gated R- and L-type Ca2+ channels, group II mGluRs, and vacuolar-type H+-ATPase, suggesting the involvement of retrograde vesicular glutamate signaling. Transsynaptic regulation of PTP extends the repertoire of synaptic computations, implementing a brake on mossy fiber detonation and a “smart teacher” function of hippocampal mossy fiber synapses. acknowledged_ssus: - _id: SSU acknowledgement: We thank Drs. Carolina Borges-Merjane and Jose Guzman for critically reading the manuscript, and Pablo Castillo for discussions. We are grateful to Alois Schlögl for help with analysis, Florian Marr for excellent technical assistance and cell reconstruction, Christina Altmutter for technical help, Eleftheria Kralli-Beller for manuscript editing, and the Scientific Service Units of IST Austria for support. This project received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement No 692692) and the Fond zur Förderung der Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein award), both to P.J. article_number: '2912' article_processing_charge: No article_type: original author: - first_name: David H full_name: Vandael, David H id: 3AE48E0A-F248-11E8-B48F-1D18A9856A87 last_name: Vandael orcid: 0000-0001-7577-1676 - first_name: Yuji full_name: Okamoto, Yuji id: 3337E116-F248-11E8-B48F-1D18A9856A87 last_name: Okamoto orcid: 0000-0003-0408-6094 - first_name: Peter M full_name: Jonas, Peter M id: 353C1B58-F248-11E8-B48F-1D18A9856A87 last_name: Jonas orcid: 0000-0001-5001-4804 citation: ama: Vandael DH, Okamoto Y, Jonas PM. Transsynaptic modulation of presynaptic short-term plasticity in hippocampal mossy fiber synapses. Nature Communications. 2021;12(1). doi:10.1038/s41467-021-23153-5 apa: Vandael, D. H., Okamoto, Y., & Jonas, P. M. (2021). Transsynaptic modulation of presynaptic short-term plasticity in hippocampal mossy fiber synapses. Nature Communications. Springer. https://doi.org/10.1038/s41467-021-23153-5 chicago: Vandael, David H, Yuji Okamoto, and Peter M Jonas. “Transsynaptic Modulation of Presynaptic Short-Term Plasticity in Hippocampal Mossy Fiber Synapses.” Nature Communications. Springer, 2021. https://doi.org/10.1038/s41467-021-23153-5. ieee: D. H. Vandael, Y. Okamoto, and P. M. Jonas, “Transsynaptic modulation of presynaptic short-term plasticity in hippocampal mossy fiber synapses,” Nature Communications, vol. 12, no. 1. Springer, 2021. ista: Vandael DH, Okamoto Y, Jonas PM. 2021. Transsynaptic modulation of presynaptic short-term plasticity in hippocampal mossy fiber synapses. Nature Communications. 12(1), 2912. mla: Vandael, David H., et al. “Transsynaptic Modulation of Presynaptic Short-Term Plasticity in Hippocampal Mossy Fiber Synapses.” Nature Communications, vol. 12, no. 1, 2912, Springer, 2021, doi:10.1038/s41467-021-23153-5. short: D.H. Vandael, Y. Okamoto, P.M. Jonas, Nature Communications 12 (2021). date_created: 2021-08-06T07:22:55Z date_published: 2021-05-18T00:00:00Z date_updated: 2023-08-10T14:16:16Z day: '18' ddc: - '570' department: - _id: PeJo doi: 10.1038/s41467-021-23153-5 ec_funded: 1 external_id: isi: - '000655481800014' file: - access_level: open_access checksum: 6036a8cdae95e1707c2a04d54e325ff4 content_type: application/pdf creator: kschuh date_created: 2021-12-17T11:34:50Z date_updated: 2021-12-17T11:34:50Z file_id: '10563' file_name: 2021_NatureCommunications_Vandael.pdf file_size: 3108845 relation: main_file success: 1 file_date_updated: 2021-12-17T11:34:50Z has_accepted_license: '1' intvolume: ' 12' isi: 1 issue: '1' keyword: - general physics and astronomy - general biochemistry - genetics and molecular biology - general chemistry language: - iso: eng month: '05' oa: 1 oa_version: Published Version project: - _id: 25B7EB9E-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '692692' name: Biophysics and circuit function of a giant cortical glumatergic synapse - _id: 25C5A090-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: Z00312 name: The Wittgenstein Prize publication: Nature Communications publication_identifier: issn: - 2041-1723 publication_status: published publisher: Springer quality_controlled: '1' related_material: link: - description: News on IST Homepage relation: press_release url: https://ist.ac.at/en/news/synaptic-transmission-not-a-one-way-street/ scopus_import: '1' status: public title: Transsynaptic modulation of presynaptic short-term plasticity in hippocampal mossy fiber synapses tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 12 year: '2021' ... --- _id: '9985' abstract: - lang: eng text: AMPA receptor (AMPAR) abundance and positioning at excitatory synapses regulates the strength of transmission. Changes in AMPAR localisation can enact synaptic plasticity, allowing long-term information storage, and is therefore tightly controlled. Multiple mechanisms regulating AMPAR synaptic anchoring have been described, but with limited coherence or comparison between reports, our understanding of this process is unclear. Here, combining synaptic recordings from mouse hippocampal slices and super-resolution imaging in dissociated cultures, we compare the contributions of three AMPAR interaction domains controlling transmission at hippocampal CA1 synapses. We show that the AMPAR C-termini play only a modulatory role, whereas the extracellular N-terminal domain (NTD) and PDZ interactions of the auxiliary subunit TARP γ8 are both crucial, and each is sufficient to maintain transmission. Our data support a model in which γ8 accumulates AMPARs at the postsynaptic density, where the NTD further tunes their positioning. This interplay between cytosolic (TARP γ8) and synaptic cleft (NTD) interactions provides versatility to regulate synaptic transmission and plasticity. acknowledgement: The authors are very grateful to Andrew Penn for advice and discussions on surface receptor labelling in slice tissue, dissociated culture transfection, and for providing tdTomato and BirAER expression plasmids. This work would not have been possible without support from the Biological Services teams at both the Laboratory of Molecular Biology and Ares facilities. We are also very grateful to Nick Barry and Jerome Boulanger of the LMB Light Microscopy facility for support with confocal and STORM imaging and analysis, Junichi Takagi for providing scFv-Clasp expression constructs, Veronica Chang for assistance with scFv-Clasp protein production, and Nejc Kejzar for assistance with cluster analysis. We would like to thank Teru Nakagawa and Ole Paulsen for critical reading of the manuscript and constructive feedback. This work was supported by grants from the Medical Research Council (MC_U105174197) and BBSRC (BB/N002113/1). article_number: '5083' article_processing_charge: Yes article_type: original author: - first_name: Jake full_name: Watson, Jake id: 63836096-4690-11EA-BD4E-32803DDC885E last_name: Watson orcid: 0000-0002-8698-3823 - first_name: Alexandra full_name: Pinggera, Alexandra last_name: Pinggera - first_name: Hinze full_name: Ho, Hinze last_name: Ho - first_name: Ingo H. full_name: Greger, Ingo H. last_name: Greger citation: ama: Watson J, Pinggera A, Ho H, Greger IH. AMPA receptor anchoring at CA1 synapses is determined by N-terminal domain and TARP γ8 interactions. Nature Communications. 2021;12(1). doi:10.1038/s41467-021-25281-4 apa: Watson, J., Pinggera, A., Ho, H., & Greger, I. H. (2021). AMPA receptor anchoring at CA1 synapses is determined by N-terminal domain and TARP γ8 interactions. Nature Communications. Nature Publishing Group. https://doi.org/10.1038/s41467-021-25281-4 chicago: Watson, Jake, Alexandra Pinggera, Hinze Ho, and Ingo H. Greger. “AMPA Receptor Anchoring at CA1 Synapses Is Determined by N-Terminal Domain and TARP Γ8 Interactions.” Nature Communications. Nature Publishing Group, 2021. https://doi.org/10.1038/s41467-021-25281-4. ieee: J. Watson, A. Pinggera, H. Ho, and I. H. Greger, “AMPA receptor anchoring at CA1 synapses is determined by N-terminal domain and TARP γ8 interactions,” Nature Communications, vol. 12, no. 1. Nature Publishing Group, 2021. ista: Watson J, Pinggera A, Ho H, Greger IH. 2021. AMPA receptor anchoring at CA1 synapses is determined by N-terminal domain and TARP γ8 interactions. Nature Communications. 12(1), 5083. mla: Watson, Jake, et al. “AMPA Receptor Anchoring at CA1 Synapses Is Determined by N-Terminal Domain and TARP Γ8 Interactions.” Nature Communications, vol. 12, no. 1, 5083, Nature Publishing Group, 2021, doi:10.1038/s41467-021-25281-4. short: J. Watson, A. Pinggera, H. Ho, I.H. Greger, Nature Communications 12 (2021). date_created: 2021-09-05T22:01:23Z date_published: 2021-08-23T00:00:00Z date_updated: 2023-08-11T11:07:51Z day: '23' ddc: - '612' department: - _id: PeJo doi: 10.1038/s41467-021-25281-4 external_id: isi: - '000687672000006' pmid: - '34426577 ' file: - access_level: open_access checksum: 1bf4f6a561f96bc426d754de9cb57710 content_type: application/pdf creator: cchlebak date_created: 2021-09-08T12:57:06Z date_updated: 2021-09-08T12:57:06Z file_id: '9991' file_name: 2021_NatureCommunications_Watson.pdf file_size: 18310502 relation: main_file success: 1 file_date_updated: 2021-09-08T12:57:06Z has_accepted_license: '1' intvolume: ' 12' isi: 1 issue: '1' language: - iso: eng month: '08' oa: 1 oa_version: Published Version pmid: 1 publication: Nature Communications publication_identifier: eissn: - 2041-1723 publication_status: published publisher: Nature Publishing Group quality_controlled: '1' scopus_import: '1' status: public title: AMPA receptor anchoring at CA1 synapses is determined by N-terminal domain and TARP γ8 interactions tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 12 year: '2021' ... --- _id: '9438' abstract: - lang: eng text: Rigorous investigation of synaptic transmission requires analysis of unitary synaptic events by simultaneous recording from presynaptic terminals and postsynaptic target neurons. However, this has been achieved at only a limited number of model synapses, including the squid giant synapse and the mammalian calyx of Held. Cortical presynaptic terminals have been largely inaccessible to direct presynaptic recording, due to their small size. Here, we describe a protocol for improved subcellular patch-clamp recording in rat and mouse brain slices, with the synapse in a largely intact environment. Slice preparation takes ~2 h, recording ~3 h and post hoc morphological analysis 2 d. Single presynaptic hippocampal mossy fiber terminals are stimulated minimally invasively in the bouton-attached configuration, in which the cytoplasmic content remains unperturbed, or in the whole-bouton configuration, in which the cytoplasmic composition can be precisely controlled. Paired pre–postsynaptic recordings can be integrated with biocytin labeling and morphological analysis, allowing correlative investigation of synapse structure and function. Paired recordings can be obtained from mossy fiber terminals in slices from both rats and mice, implying applicability to genetically modified synapses. Paired recordings can also be performed together with axon tract stimulation or optogenetic activation, allowing comparison of unitary and compound synaptic events in the same target cell. Finally, paired recordings can be combined with spontaneous event analysis, permitting collection of miniature events generated at a single identified synapse. In conclusion, the subcellular patch-clamp techniques detailed here should facilitate analysis of biophysics, plasticity and circuit function of cortical synapses in the mammalian central nervous system. acknowledged_ssus: - _id: M-Shop acknowledgement: This project received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 692692 to P.J.) and the Fond zur Förderung der Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein award to P.J., V 739-B27 to C.B.M.). We are grateful to F. Marr and C. Altmutter for excellent technical assistance and cell reconstruction, E. Kralli-Beller for manuscript editing, and the Scientific Service Units of IST Austria, especially T. Asenov and Miba machine shop, for maximally efficient support. article_processing_charge: No article_type: original author: - first_name: David H full_name: Vandael, David H id: 3AE48E0A-F248-11E8-B48F-1D18A9856A87 last_name: Vandael orcid: 0000-0001-7577-1676 - first_name: Yuji full_name: Okamoto, Yuji id: 3337E116-F248-11E8-B48F-1D18A9856A87 last_name: Okamoto orcid: 0000-0003-0408-6094 - first_name: Carolina full_name: Borges Merjane, Carolina id: 4305C450-F248-11E8-B48F-1D18A9856A87 last_name: Borges Merjane orcid: 0000-0003-0005-401X - first_name: Victor M full_name: Vargas Barroso, Victor M id: 2F55A9DE-F248-11E8-B48F-1D18A9856A87 last_name: Vargas Barroso - first_name: Benjamin full_name: Suter, Benjamin id: 4952F31E-F248-11E8-B48F-1D18A9856A87 last_name: Suter orcid: 0000-0002-9885-6936 - first_name: Peter M full_name: Jonas, Peter M id: 353C1B58-F248-11E8-B48F-1D18A9856A87 last_name: Jonas orcid: 0000-0001-5001-4804 citation: ama: Vandael DH, Okamoto Y, Borges Merjane C, Vargas Barroso VM, Suter B, Jonas PM. Subcellular patch-clamp techniques for single-bouton stimulation and simultaneous pre- and postsynaptic recording at cortical synapses. Nature Protocols. 2021;16(6):2947–2967. doi:10.1038/s41596-021-00526-0 apa: Vandael, D. H., Okamoto, Y., Borges Merjane, C., Vargas Barroso, V. M., Suter, B., & Jonas, P. M. (2021). Subcellular patch-clamp techniques for single-bouton stimulation and simultaneous pre- and postsynaptic recording at cortical synapses. Nature Protocols. Springer Nature. https://doi.org/10.1038/s41596-021-00526-0 chicago: Vandael, David H, Yuji Okamoto, Carolina Borges Merjane, Victor M Vargas Barroso, Benjamin Suter, and Peter M Jonas. “Subcellular Patch-Clamp Techniques for Single-Bouton Stimulation and Simultaneous Pre- and Postsynaptic Recording at Cortical Synapses.” Nature Protocols. Springer Nature, 2021. https://doi.org/10.1038/s41596-021-00526-0. ieee: D. H. Vandael, Y. Okamoto, C. Borges Merjane, V. M. Vargas Barroso, B. Suter, and P. M. Jonas, “Subcellular patch-clamp techniques for single-bouton stimulation and simultaneous pre- and postsynaptic recording at cortical synapses,” Nature Protocols, vol. 16, no. 6. Springer Nature, pp. 2947–2967, 2021. ista: Vandael DH, Okamoto Y, Borges Merjane C, Vargas Barroso VM, Suter B, Jonas PM. 2021. Subcellular patch-clamp techniques for single-bouton stimulation and simultaneous pre- and postsynaptic recording at cortical synapses. Nature Protocols. 16(6), 2947–2967. mla: Vandael, David H., et al. “Subcellular Patch-Clamp Techniques for Single-Bouton Stimulation and Simultaneous Pre- and Postsynaptic Recording at Cortical Synapses.” Nature Protocols, vol. 16, no. 6, Springer Nature, 2021, pp. 2947–2967, doi:10.1038/s41596-021-00526-0. short: D.H. Vandael, Y. Okamoto, C. Borges Merjane, V.M. Vargas Barroso, B. Suter, P.M. Jonas, Nature Protocols 16 (2021) 2947–2967. date_created: 2021-05-30T22:01:24Z date_published: 2021-06-01T00:00:00Z date_updated: 2023-08-10T22:30:51Z day: '01' ddc: - '570' department: - _id: PeJo doi: 10.1038/s41596-021-00526-0 ec_funded: 1 external_id: isi: - '000650528700003' pmid: - '33990799' file: - access_level: open_access checksum: 7eb580abd8893cdb0b410cf41bc8c263 content_type: application/pdf creator: cziletti date_created: 2021-07-08T12:27:55Z date_updated: 2021-12-02T23:30:05Z embargo: 2021-12-01 file_id: '9639' file_name: VandaeletalAuthorVersion2021.pdf file_size: 38574802 relation: main_file file_date_updated: 2021-12-02T23:30:05Z has_accepted_license: '1' intvolume: ' 16' isi: 1 issue: '6' language: - iso: eng month: '06' oa: 1 oa_version: Submitted Version page: 2947–2967 pmid: 1 project: - _id: 25B7EB9E-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '692692' name: Biophysics and circuit function of a giant cortical glumatergic synapse - _id: 25C5A090-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: Z00312 name: The Wittgenstein Prize - _id: 2696E7FE-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: V00739 name: Structural plasticity at mossy fiber-CA3 synapses publication: Nature Protocols publication_identifier: eissn: - '17502799' issn: - '17542189' publication_status: published publisher: Springer Nature quality_controlled: '1' scopus_import: '1' status: public title: Subcellular patch-clamp techniques for single-bouton stimulation and simultaneous pre- and postsynaptic recording at cortical synapses type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 16 year: '2021' ... --- _id: '10816' abstract: - lang: eng text: Pattern separation is a fundamental brain computation that converts small differences in input patterns into large differences in output patterns. Several synaptic mechanisms of pattern separation have been proposed, including code expansion, inhibition and plasticity; however, which of these mechanisms play a role in the entorhinal cortex (EC)–dentate gyrus (DG)–CA3 circuit, a classical pattern separation circuit, remains unclear. Here we show that a biologically realistic, full-scale EC–DG–CA3 circuit model, including granule cells (GCs) and parvalbumin-positive inhibitory interneurons (PV+-INs) in the DG, is an efficient pattern separator. Both external gamma-modulated inhibition and internal lateral inhibition mediated by PV+-INs substantially contributed to pattern separation. Both local connectivity and fast signaling at GC–PV+-IN synapses were important for maximum effectiveness. Similarly, mossy fiber synapses with conditional detonator properties contributed to pattern separation. By contrast, perforant path synapses with Hebbian synaptic plasticity and direct EC–CA3 connection shifted the network towards pattern completion. Our results demonstrate that the specific properties of cells and synapses optimize higher-order computations in biological networks and might be useful to improve the deep learning capabilities of technical networks. acknowledged_ssus: - _id: SSU acknowledgement: We thank A. Aertsen, N. Kopell, W. Maass, A. Roth, F. Stella and T. Vogels for critically reading earlier versions of the manuscript. We are grateful to F. Marr and C. Altmutter for excellent technical assistance, E. Kralli-Beller for manuscript editing, and the Scientific Service Units of IST Austria for efficient support. Finally, we thank T. Carnevale, L. Erdös, M. Hines, D. Nykamp and D. Schröder for useful discussions, and R. Friedrich and S. Wiechert for sharing unpublished data. This project received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 692692, P.J.) and the Fond zur Förderung der Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein award to P.J. and P 31815 to S.J.G.). article_processing_charge: No article_type: original author: - first_name: José full_name: Guzmán, José id: 30CC5506-F248-11E8-B48F-1D18A9856A87 last_name: Guzmán orcid: 0000-0003-2209-5242 - first_name: Alois full_name: Schlögl, Alois id: 45BF87EE-F248-11E8-B48F-1D18A9856A87 last_name: Schlögl orcid: 0000-0002-5621-8100 - first_name: 'Claudia ' full_name: 'Espinoza Martinez, Claudia ' id: 31FFEE2E-F248-11E8-B48F-1D18A9856A87 last_name: Espinoza Martinez orcid: 0000-0003-4710-2082 - first_name: Xiaomin full_name: Zhang, Xiaomin id: 423EC9C2-F248-11E8-B48F-1D18A9856A87 last_name: Zhang - first_name: Benjamin full_name: Suter, Benjamin id: 4952F31E-F248-11E8-B48F-1D18A9856A87 last_name: Suter orcid: 0000-0002-9885-6936 - first_name: Peter M full_name: Jonas, Peter M id: 353C1B58-F248-11E8-B48F-1D18A9856A87 last_name: Jonas orcid: 0000-0001-5001-4804 citation: ama: Guzmán J, Schlögl A, Espinoza Martinez C, Zhang X, Suter B, Jonas PM. How connectivity rules and synaptic properties shape the efficacy of pattern separation in the entorhinal cortex–dentate gyrus–CA3 network. Nature Computational Science. 2021;1(12):830-842. doi:10.1038/s43588-021-00157-1 apa: Guzmán, J., Schlögl, A., Espinoza Martinez, C., Zhang, X., Suter, B., & Jonas, P. M. (2021). How connectivity rules and synaptic properties shape the efficacy of pattern separation in the entorhinal cortex–dentate gyrus–CA3 network. Nature Computational Science. Springer Nature. https://doi.org/10.1038/s43588-021-00157-1 chicago: Guzmán, José, Alois Schlögl, Claudia Espinoza Martinez, Xiaomin Zhang, Benjamin Suter, and Peter M Jonas. “How Connectivity Rules and Synaptic Properties Shape the Efficacy of Pattern Separation in the Entorhinal Cortex–Dentate Gyrus–CA3 Network.” Nature Computational Science. Springer Nature, 2021. https://doi.org/10.1038/s43588-021-00157-1. ieee: J. Guzmán, A. Schlögl, C. Espinoza Martinez, X. Zhang, B. Suter, and P. M. Jonas, “How connectivity rules and synaptic properties shape the efficacy of pattern separation in the entorhinal cortex–dentate gyrus–CA3 network,” Nature Computational Science, vol. 1, no. 12. Springer Nature, pp. 830–842, 2021. ista: Guzmán J, Schlögl A, Espinoza Martinez C, Zhang X, Suter B, Jonas PM. 2021. How connectivity rules and synaptic properties shape the efficacy of pattern separation in the entorhinal cortex–dentate gyrus–CA3 network. Nature Computational Science. 1(12), 830–842. mla: Guzmán, José, et al. “How Connectivity Rules and Synaptic Properties Shape the Efficacy of Pattern Separation in the Entorhinal Cortex–Dentate Gyrus–CA3 Network.” Nature Computational Science, vol. 1, no. 12, Springer Nature, 2021, pp. 830–42, doi:10.1038/s43588-021-00157-1. short: J. Guzmán, A. Schlögl, C. Espinoza Martinez, X. Zhang, B. Suter, P.M. Jonas, Nature Computational Science 1 (2021) 830–842. date_created: 2022-03-04T08:32:36Z date_published: 2021-12-16T00:00:00Z date_updated: 2023-08-10T22:30:10Z day: '16' ddc: - '610' department: - _id: PeJo doi: 10.1038/s43588-021-00157-1 ec_funded: 1 file: - access_level: open_access checksum: 9fec5b667909ef52be96d502e4f8c2ae content_type: application/pdf creator: patrickd date_created: 2022-06-02T12:51:07Z date_updated: 2022-06-18T22:30:03Z embargo: 2022-06-17 file_id: '11430' file_name: Guzmanetal2021.pdf file_size: 1699466 relation: main_file - access_level: open_access checksum: 52a005b13a114e3c3a28fa6bbe8b1a8d content_type: application/pdf creator: patrickd date_created: 2022-06-02T12:53:47Z date_updated: 2022-06-18T22:30:03Z embargo: 2022-06-17 file_id: '11431' file_name: Guzmanetal2021Suppl.pdf file_size: 3005651 relation: supplementary_material title: Supplementary Material file_date_updated: 2022-06-18T22:30:03Z has_accepted_license: '1' intvolume: ' 1' issue: '12' keyword: - general medicine language: - iso: eng main_file_link: - open_access: '1' url: https://www.biorxiv.org/content/10.1101/647800 month: '12' oa: 1 oa_version: Submitted Version page: 830-842 project: - _id: 25B7EB9E-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '692692' name: Biophysics and circuit function of a giant cortical glumatergic synapse - _id: 25C5A090-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: Z00312 name: The Wittgenstein Prize publication: Nature Computational Science publication_identifier: issn: - 2662-8457 publication_status: published publisher: Springer Nature quality_controlled: '1' related_material: link: - relation: press_release url: https://ista.ac.at/en/news/spot-the-difference/ record: - id: '10110' relation: software status: public scopus_import: '1' status: public title: How connectivity rules and synaptic properties shape the efficacy of pattern separation in the entorhinal cortex–dentate gyrus–CA3 network type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 1 year: '2021' ... --- _id: '10110' abstract: - lang: eng text: Pattern separation is a fundamental brain computation that converts small differences in input patterns into large differences in output patterns. Several synaptic mechanisms of pattern separation have been proposed, including code expansion, inhibition and plasticity; however, which of these mechanisms play a role in the entorhinal cortex (EC)–dentate gyrus (DG)–CA3 circuit, a classical pattern separation circuit, remains unclear. Here we show that a biologically realistic, full-scale EC–DG–CA3 circuit model, including granule cells (GCs) and parvalbumin-positive inhibitory interneurons (PV+-INs) in the DG, is an efficient pattern separator. Both external gamma-modulated inhibition and internal lateral inhibition mediated by PV+-INs substantially contributed to pattern separation. Both local connectivity and fast signaling at GC–PV+-IN synapses were important for maximum effectiveness. Similarly, mossy fiber synapses with conditional detonator properties contributed to pattern separation. By contrast, perforant path synapses with Hebbian synaptic plasticity and direct EC–CA3 connection shifted the network towards pattern completion. Our results demonstrate that the specific properties of cells and synapses optimize higher-order computations in biological networks and might be useful to improve the deep learning capabilities of technical networks. author: - first_name: José full_name: Guzmán, José id: 30CC5506-F248-11E8-B48F-1D18A9856A87 last_name: Guzmán orcid: 0000-0003-2209-5242 - first_name: Alois full_name: Schlögl, Alois id: 45BF87EE-F248-11E8-B48F-1D18A9856A87 last_name: Schlögl orcid: 0000-0002-5621-8100 - first_name: 'Claudia ' full_name: 'Espinoza Martinez, Claudia ' id: 31FFEE2E-F248-11E8-B48F-1D18A9856A87 last_name: Espinoza Martinez orcid: 0000-0003-4710-2082 - first_name: Xiaomin full_name: Zhang, Xiaomin id: 423EC9C2-F248-11E8-B48F-1D18A9856A87 last_name: Zhang - first_name: Benjamin full_name: Suter, Benjamin id: 4952F31E-F248-11E8-B48F-1D18A9856A87 last_name: Suter orcid: 0000-0002-9885-6936 - first_name: Peter M full_name: Jonas, Peter M id: 353C1B58-F248-11E8-B48F-1D18A9856A87 last_name: Jonas orcid: 0000-0001-5001-4804 citation: ama: Guzmán J, Schlögl A, Espinoza Martinez C, Zhang X, Suter B, Jonas PM. How connectivity rules and synaptic properties shape the efficacy of pattern separation in the entorhinal cortex–dentate gyrus–CA3 network. 2021. doi:10.15479/AT:ISTA:10110 apa: Guzmán, J., Schlögl, A., Espinoza Martinez, C., Zhang, X., Suter, B., & Jonas, P. M. (2021). How connectivity rules and synaptic properties shape the efficacy of pattern separation in the entorhinal cortex–dentate gyrus–CA3 network. IST Austria. https://doi.org/10.15479/AT:ISTA:10110 chicago: Guzmán, José, Alois Schlögl, Claudia Espinoza Martinez, Xiaomin Zhang, Benjamin Suter, and Peter M Jonas. “How Connectivity Rules and Synaptic Properties Shape the Efficacy of Pattern Separation in the Entorhinal Cortex–Dentate Gyrus–CA3 Network.” IST Austria, 2021. https://doi.org/10.15479/AT:ISTA:10110. ieee: J. Guzmán, A. Schlögl, C. Espinoza Martinez, X. Zhang, B. Suter, and P. M. Jonas, “How connectivity rules and synaptic properties shape the efficacy of pattern separation in the entorhinal cortex–dentate gyrus–CA3 network.” IST Austria, 2021. ista: Guzmán J, Schlögl A, Espinoza Martinez C, Zhang X, Suter B, Jonas PM. 2021. How connectivity rules and synaptic properties shape the efficacy of pattern separation in the entorhinal cortex–dentate gyrus–CA3 network, IST Austria, 10.15479/AT:ISTA:10110. mla: Guzmán, José, et al. How Connectivity Rules and Synaptic Properties Shape the Efficacy of Pattern Separation in the Entorhinal Cortex–Dentate Gyrus–CA3 Network. IST Austria, 2021, doi:10.15479/AT:ISTA:10110. short: J. Guzmán, A. Schlögl, C. Espinoza Martinez, X. Zhang, B. Suter, P.M. Jonas, (2021). date_created: 2021-10-08T06:44:22Z date_published: 2021-12-16T00:00:00Z date_updated: 2024-03-27T23:30:11Z day: '16' ddc: - '005' department: - _id: PeJo - _id: ScienComp doi: 10.15479/AT:ISTA:10110 file: - access_level: open_access checksum: f92f8931cad0aa7e411c1715337bf408 content_type: application/x-zip-compressed creator: cchlebak date_created: 2021-10-08T08:46:04Z date_updated: 2021-10-08T08:46:04Z file_id: '10114' file_name: patternseparation-main (1).zip file_size: 332990101 relation: main_file success: 1 file_date_updated: 2021-10-08T08:46:04Z has_accepted_license: '1' license: https://opensource.org/licenses/GPL-3.0 month: '12' oa: 1 publisher: IST Austria related_material: link: - description: News on IST Webpage relation: press_release url: https://ist.ac.at/en/news/spot-the-difference/ record: - id: '10816' relation: used_for_analysis_in status: public status: public title: How connectivity rules and synaptic properties shape the efficacy of pattern separation in the entorhinal cortex–dentate gyrus–CA3 network tmp: legal_code_url: https://www.gnu.org/licenses/gpl-3.0.en.html name: GNU General Public License 3.0 short: GPL 3.0 type: software user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9 year: '2021' ... --- _id: '9437' abstract: - lang: eng text: The synaptic connection from medial habenula (MHb) to interpeduncular nucleus (IPN) is critical for emotion-related behaviors and uniquely expresses R-type Ca2+ channels (Cav2.3) and auxiliary GABAB receptor (GBR) subunits, the K+-channel tetramerization domain-containing proteins (KCTDs). Activation of GBRs facilitates or inhibits transmitter release from MHb terminals depending on the IPN subnucleus, but the role of KCTDs is unknown. We therefore examined the localization and function of Cav2.3, GBRs, and KCTDs in this pathway in mice. We show in heterologous cells that KCTD8 and KCTD12b directly bind to Cav2.3 and that KCTD8 potentiates Cav2.3 currents in the absence of GBRs. In the rostral IPN, KCTD8, KCTD12b, and Cav2.3 co-localize at the presynaptic active zone. Genetic deletion indicated a bidirectional modulation of Cav2.3-mediated release by these KCTDs with a compensatory increase of KCTD8 in the active zone in KCTD12b-deficient mice. The interaction of Cav2.3 with KCTDs therefore scales synaptic strength independent of GBR activation. acknowledgement: We are grateful to Akari Hagiwara and Toshihisa Ohtsuka for CAST antibody, and Masahiko Watanabe for neurexin antibody. We thank David Adams for kindly providing the stable Cav2.3 cell line. Cav2.3 KO mice were kindly provided by Tsutomu Tanabe. This project has received funding from the European Research Council (ERC) and European Commission (EC), under the European Union’s Horizon 2020 research and innovation programme (ERC grant agreement no. 694539 to Ryuichi Shigemoto, no. 692692 to Peter Jonas, and the Marie Skłodowska-Curie grant agreement no. 665385 to Cihan Önal), the Swiss National Science Foundation Grant 31003A-172881 to Bernhard Bettler and Deutsche Forschungsgemeinschaft (For 2143) and BIOSS-2 to Akos Kulik. article_number: e68274 article_processing_charge: No article_type: original author: - first_name: Pradeep full_name: Bhandari, Pradeep id: 45EDD1BC-F248-11E8-B48F-1D18A9856A87 last_name: Bhandari orcid: 0000-0003-0863-4481 - first_name: David H full_name: Vandael, David H id: 3AE48E0A-F248-11E8-B48F-1D18A9856A87 last_name: Vandael orcid: 0000-0001-7577-1676 - first_name: Diego full_name: Fernández-Fernández, Diego last_name: Fernández-Fernández - first_name: Thorsten full_name: Fritzius, Thorsten last_name: Fritzius - first_name: David full_name: Kleindienst, David id: 42E121A4-F248-11E8-B48F-1D18A9856A87 last_name: Kleindienst - first_name: Hüseyin C full_name: Önal, Hüseyin C id: 4659D740-F248-11E8-B48F-1D18A9856A87 last_name: Önal orcid: 0000-0002-2771-2011 - first_name: Jacqueline-Claire full_name: Montanaro-Punzengruber, Jacqueline-Claire id: 3786AB44-F248-11E8-B48F-1D18A9856A87 last_name: Montanaro-Punzengruber - first_name: Martin full_name: Gassmann, Martin last_name: Gassmann - first_name: Peter M full_name: Jonas, Peter M id: 353C1B58-F248-11E8-B48F-1D18A9856A87 last_name: Jonas orcid: 0000-0001-5001-4804 - first_name: Akos full_name: Kulik, Akos last_name: Kulik - first_name: Bernhard full_name: Bettler, Bernhard last_name: Bettler - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 - first_name: Peter full_name: Koppensteiner, Peter id: 3B8B25A8-F248-11E8-B48F-1D18A9856A87 last_name: Koppensteiner orcid: 0000-0002-3509-1948 citation: ama: Bhandari P, Vandael DH, Fernández-Fernández D, et al. GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals. eLife. 2021;10. doi:10.7554/ELIFE.68274 apa: Bhandari, P., Vandael, D. H., Fernández-Fernández, D., Fritzius, T., Kleindienst, D., Önal, H. C., … Koppensteiner, P. (2021). GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals. ELife. eLife Sciences Publications. https://doi.org/10.7554/ELIFE.68274 chicago: Bhandari, Pradeep, David H Vandael, Diego Fernández-Fernández, Thorsten Fritzius, David Kleindienst, Hüseyin C Önal, Jacqueline-Claire Montanaro-Punzengruber, et al. “GABAB Receptor Auxiliary Subunits Modulate Cav2.3-Mediated Release from Medial Habenula Terminals.” ELife. eLife Sciences Publications, 2021. https://doi.org/10.7554/ELIFE.68274. ieee: P. Bhandari et al., “GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals,” eLife, vol. 10. eLife Sciences Publications, 2021. ista: Bhandari P, Vandael DH, Fernández-Fernández D, Fritzius T, Kleindienst D, Önal HC, Montanaro-Punzengruber J-C, Gassmann M, Jonas PM, Kulik A, Bettler B, Shigemoto R, Koppensteiner P. 2021. GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals. eLife. 10, e68274. mla: Bhandari, Pradeep, et al. “GABAB Receptor Auxiliary Subunits Modulate Cav2.3-Mediated Release from Medial Habenula Terminals.” ELife, vol. 10, e68274, eLife Sciences Publications, 2021, doi:10.7554/ELIFE.68274. short: P. Bhandari, D.H. Vandael, D. Fernández-Fernández, T. Fritzius, D. Kleindienst, H.C. Önal, J.-C. Montanaro-Punzengruber, M. Gassmann, P.M. Jonas, A. Kulik, B. Bettler, R. Shigemoto, P. Koppensteiner, ELife 10 (2021). date_created: 2021-05-30T22:01:23Z date_published: 2021-04-29T00:00:00Z date_updated: 2024-03-27T23:30:30Z day: '29' ddc: - '570' department: - _id: RySh - _id: PeJo doi: 10.7554/ELIFE.68274 ec_funded: 1 external_id: isi: - '000651761700001' file: - access_level: open_access checksum: 6ebcb79999f889766f7cd79ee134ad28 content_type: application/pdf creator: cziletti date_created: 2021-05-31T09:43:09Z date_updated: 2021-05-31T09:43:09Z file_id: '9440' file_name: 2021_eLife_Bhandari.pdf file_size: 8174719 relation: main_file success: 1 file_date_updated: 2021-05-31T09:43:09Z has_accepted_license: '1' intvolume: ' 10' isi: 1 language: - iso: eng month: '04' oa: 1 oa_version: Published Version project: - _id: 25CA28EA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '694539' name: 'In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour' - _id: 25B7EB9E-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '692692' name: Biophysics and circuit function of a giant cortical glumatergic synapse - _id: 2564DBCA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '665385' name: International IST Doctoral Program publication: eLife publication_identifier: eissn: - 2050-084X publication_status: published publisher: eLife Sciences Publications quality_controlled: '1' related_material: link: - relation: earlier_version url: https://doi.org/10.1101/2020.04.16.045112 record: - id: '9562' relation: dissertation_contains status: public scopus_import: '1' status: public title: GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 10 year: '2021' ... --- _id: '8001' abstract: - lang: eng text: Post-tetanic potentiation (PTP) is an attractive candidate mechanism for hippocampus-dependent short-term memory. Although PTP has a uniquely large magnitude at hippocampal mossy fiber-CA3 pyramidal neuron synapses, it is unclear whether it can be induced by natural activity and whether its lifetime is sufficient to support short-term memory. We combined in vivo recordings from granule cells (GCs), in vitro paired recordings from mossy fiber terminals and postsynaptic CA3 neurons, and “flash and freeze” electron microscopy. PTP was induced at single synapses and showed a low induction threshold adapted to sparse GC activity in vivo. PTP was mainly generated by enlargement of the readily releasable pool of synaptic vesicles, allowing multiplicative interaction with other plasticity forms. PTP was associated with an increase in the docked vesicle pool, suggesting formation of structural “pool engrams.” Absence of presynaptic activity extended the lifetime of the potentiation, enabling prolonged information storage in the hippocampal network. acknowledged_ssus: - _id: SSU acknowledgement: This project received funding from the European Research Council (ERC) under the European Union Horizon 2020 Research and Innovation Program (grant agreement 692692 to P.J.) and the Fond zur Förderung der Wissenschaftlichen Forschung ( Z 312-B27 , Wittgenstein award to P.J. and V 739-B27 to C.B.-M.). We thank Drs. Jozsef Csicsvari, Jose Guzman, Erwin Neher, and Ryuichi Shigemoto for commenting on earlier versions of the manuscript. We are grateful to Walter Kaufmann, Daniel Gütl, and Vanessa Zheden for EM training; Alois Schlögl for programming; Florian Marr for excellent technical assistance and cell reconstruction; Christina Altmutter for technical help; Eleftheria Kralli-Beller for manuscript editing; Taija Makinen for providing the Prox1-CreERT2 mouse line; and the Scientific Service Units of IST Austria for support. article_processing_charge: No article_type: original author: - first_name: David H full_name: Vandael, David H id: 3AE48E0A-F248-11E8-B48F-1D18A9856A87 last_name: Vandael orcid: 0000-0001-7577-1676 - first_name: Carolina full_name: Borges Merjane, Carolina id: 4305C450-F248-11E8-B48F-1D18A9856A87 last_name: Borges Merjane orcid: 0000-0003-0005-401X - first_name: Xiaomin full_name: Zhang, Xiaomin id: 423EC9C2-F248-11E8-B48F-1D18A9856A87 last_name: Zhang - first_name: Peter M full_name: Jonas, Peter M id: 353C1B58-F248-11E8-B48F-1D18A9856A87 last_name: Jonas orcid: 0000-0001-5001-4804 citation: ama: Vandael DH, Borges Merjane C, Zhang X, Jonas PM. Short-term plasticity at hippocampal mossy fiber synapses is induced by natural activity patterns and associated with vesicle pool engram formation. Neuron. 2020;107(3):509-521. doi:10.1016/j.neuron.2020.05.013 apa: Vandael, D. H., Borges Merjane, C., Zhang, X., & Jonas, P. M. (2020). Short-term plasticity at hippocampal mossy fiber synapses is induced by natural activity patterns and associated with vesicle pool engram formation. Neuron. Elsevier. https://doi.org/10.1016/j.neuron.2020.05.013 chicago: Vandael, David H, Carolina Borges Merjane, Xiaomin Zhang, and Peter M Jonas. “Short-Term Plasticity at Hippocampal Mossy Fiber Synapses Is Induced by Natural Activity Patterns and Associated with Vesicle Pool Engram Formation.” Neuron. Elsevier, 2020. https://doi.org/10.1016/j.neuron.2020.05.013. ieee: D. H. Vandael, C. Borges Merjane, X. Zhang, and P. M. Jonas, “Short-term plasticity at hippocampal mossy fiber synapses is induced by natural activity patterns and associated with vesicle pool engram formation,” Neuron, vol. 107, no. 3. Elsevier, pp. 509–521, 2020. ista: Vandael DH, Borges Merjane C, Zhang X, Jonas PM. 2020. Short-term plasticity at hippocampal mossy fiber synapses is induced by natural activity patterns and associated with vesicle pool engram formation. Neuron. 107(3), 509–521. mla: Vandael, David H., et al. “Short-Term Plasticity at Hippocampal Mossy Fiber Synapses Is Induced by Natural Activity Patterns and Associated with Vesicle Pool Engram Formation.” Neuron, vol. 107, no. 3, Elsevier, 2020, pp. 509–21, doi:10.1016/j.neuron.2020.05.013. short: D.H. Vandael, C. Borges Merjane, X. Zhang, P.M. Jonas, Neuron 107 (2020) 509–521. date_created: 2020-06-22T13:29:05Z date_published: 2020-08-05T00:00:00Z date_updated: 2023-08-22T07:45:25Z day: '05' ddc: - '570' department: - _id: PeJo doi: 10.1016/j.neuron.2020.05.013 ec_funded: 1 external_id: isi: - '000556135600004' pmid: - '32492366' file: - access_level: open_access checksum: 4030b2be0c9625d54694a1e9fb00305e content_type: application/pdf creator: dernst date_created: 2020-11-25T11:23:02Z date_updated: 2020-11-25T11:23:02Z file_id: '8811' file_name: 2020_Neuron_Vandael.pdf file_size: 4390833 relation: main_file success: 1 file_date_updated: 2020-11-25T11:23:02Z has_accepted_license: '1' intvolume: ' 107' isi: 1 issue: '3' language: - iso: eng license: https://creativecommons.org/licenses/by-nc-nd/4.0/ month: '08' oa: 1 oa_version: Published Version page: 509-521 pmid: 1 project: - _id: 25B7EB9E-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '692692' name: Biophysics and circuit function of a giant cortical glumatergic synapse - _id: 25C5A090-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: Z00312 name: The Wittgenstein Prize - _id: 2696E7FE-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: V00739 name: Structural plasticity at mossy fiber-CA3 synapses publication: Neuron publication_identifier: eissn: - '10974199' issn: - 0896-6273 publication_status: published publisher: Elsevier quality_controlled: '1' related_material: link: - description: News on IST Homepage relation: press_release url: https://ist.ac.at/en/news/possible-physical-trace-of-short-term-memory-found/ scopus_import: '1' status: public title: Short-term plasticity at hippocampal mossy fiber synapses is induced by natural activity patterns and associated with vesicle pool engram formation tmp: image: /images/cc_by_nc_nd.png legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) short: CC BY-NC-ND (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 107 year: '2020' ... --- _id: '8261' abstract: - lang: eng text: Dentate gyrus granule cells (GCs) connect the entorhinal cortex to the hippocampal CA3 region, but how they process spatial information remains enigmatic. To examine the role of GCs in spatial coding, we measured excitatory postsynaptic potentials (EPSPs) and action potentials (APs) in head-fixed mice running on a linear belt. Intracellular recording from morphologically identified GCs revealed that most cells were active, but activity level varied over a wide range. Whereas only ∼5% of GCs showed spatially tuned spiking, ∼50% received spatially tuned input. Thus, the GC population broadly encodes spatial information, but only a subset relays this information to the CA3 network. Fourier analysis indicated that GCs received conjunctive place-grid-like synaptic input, suggesting code conversion in single neurons. GC firing was correlated with dendritic complexity and intrinsic excitability, but not extrinsic excitatory input or dendritic cable properties. Thus, functional maturation may control input-output transformation and spatial code conversion. acknowledged_ssus: - _id: M-Shop - _id: ScienComp - _id: PreCl acknowledgement: This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement 692692, P.J.) and the Fond zur Förderung der Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein award, P.J.). We thank Gyorgy Buzsáki, Jozsef Csicsvari, Juan Ramirez Villegas, and Federico Stella for commenting on earlier versions of this manuscript. We also thank Katie Bittner, Michael Brecht, Albert Lee, Jeffery Magee, and Alejandro Pernía-Andrade for sharing expertise in in vivo patch-clamp recording. We are grateful to Florian Marr for cell labeling, cell reconstruction, and technical assistance; Ben Suter for helpful discussions; Christina Altmutter for technical support; Eleftheria Kralli-Beller for manuscript editing; and Todor Asenov (Machine Shop) for device construction. We also thank the Scientific Service Units (SSUs) of IST Austria (Machine Shop, Scientific Computing, and Preclinical Facility) for efficient support. article_processing_charge: No article_type: original author: - first_name: Xiaomin full_name: Zhang, Xiaomin id: 423EC9C2-F248-11E8-B48F-1D18A9856A87 last_name: Zhang - first_name: Alois full_name: Schlögl, Alois id: 45BF87EE-F248-11E8-B48F-1D18A9856A87 last_name: Schlögl orcid: 0000-0002-5621-8100 - first_name: Peter M full_name: Jonas, Peter M id: 353C1B58-F248-11E8-B48F-1D18A9856A87 last_name: Jonas orcid: 0000-0001-5001-4804 citation: ama: Zhang X, Schlögl A, Jonas PM. Selective routing of spatial information flow from input to output in hippocampal granule cells. Neuron. 2020;107(6):1212-1225. doi:10.1016/j.neuron.2020.07.006 apa: Zhang, X., Schlögl, A., & Jonas, P. M. (2020). Selective routing of spatial information flow from input to output in hippocampal granule cells. Neuron. Elsevier. https://doi.org/10.1016/j.neuron.2020.07.006 chicago: Zhang, Xiaomin, Alois Schlögl, and Peter M Jonas. “Selective Routing of Spatial Information Flow from Input to Output in Hippocampal Granule Cells.” Neuron. Elsevier, 2020. https://doi.org/10.1016/j.neuron.2020.07.006. ieee: X. Zhang, A. Schlögl, and P. M. Jonas, “Selective routing of spatial information flow from input to output in hippocampal granule cells,” Neuron, vol. 107, no. 6. Elsevier, pp. 1212–1225, 2020. ista: Zhang X, Schlögl A, Jonas PM. 2020. Selective routing of spatial information flow from input to output in hippocampal granule cells. Neuron. 107(6), 1212–1225. mla: Zhang, Xiaomin, et al. “Selective Routing of Spatial Information Flow from Input to Output in Hippocampal Granule Cells.” Neuron, vol. 107, no. 6, Elsevier, 2020, pp. 1212–25, doi:10.1016/j.neuron.2020.07.006. short: X. Zhang, A. Schlögl, P.M. Jonas, Neuron 107 (2020) 1212–1225. date_created: 2020-08-14T09:36:05Z date_published: 2020-09-23T00:00:00Z date_updated: 2023-08-22T08:30:55Z day: '23' ddc: - '570' department: - _id: PeJo - _id: ScienComp doi: 10.1016/j.neuron.2020.07.006 ec_funded: 1 external_id: isi: - '000579698700009' pmid: - '32763145' file: - access_level: open_access checksum: 44a5960fc083a4cb3488d22224859fdc content_type: application/pdf creator: dernst date_created: 2020-12-04T09:29:21Z date_updated: 2020-12-04T09:29:21Z file_id: '8920' file_name: 2020_Neuron_Zhang.pdf file_size: 3011120 relation: main_file success: 1 file_date_updated: 2020-12-04T09:29:21Z has_accepted_license: '1' intvolume: ' 107' isi: 1 issue: '6' language: - iso: eng month: '09' oa: 1 oa_version: Published Version page: 1212-1225 pmid: 1 project: - _id: 25B7EB9E-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '692692' name: Biophysics and circuit function of a giant cortical glumatergic synapse - _id: 25C5A090-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: Z00312 name: The Wittgenstein Prize publication: Neuron publication_identifier: issn: - 0896-6273 publication_status: published publisher: Elsevier quality_controlled: '1' related_material: link: - description: News on IST Website relation: press_release url: https://ist.ac.at/en/news/the-bouncer-in-the-brain/ status: public title: Selective routing of spatial information flow from input to output in hippocampal granule cells tmp: image: /images/cc_by_nc_nd.png legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) short: CC BY-NC-ND (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 107 year: '2020' ... --- _id: '7473' abstract: - lang: eng text: How structural and functional properties of synapses relate to each other is a fundamental question in neuroscience. Electrophysiology has elucidated mechanisms of synaptic transmission, and electron microscopy (EM) has provided insight into morphological properties of synapses. Here we describe an enhanced method for functional EM (“flash and freeze”), combining optogenetic stimulation with high-pressure freezing. We demonstrate that the improved method can be applied to intact networks in acute brain slices and organotypic slice cultures from mice. As a proof of concept, we probed vesicle pool changes during synaptic transmission at the hippocampal mossy fiber-CA3 pyramidal neuron synapse. Our findings show overlap of the docked vesicle pool and the functionally defined readily releasable pool and provide evidence of fast endocytosis at this synapse. Functional EM with acute slices and slice cultures has the potential to reveal the structural and functional mechanisms of transmission in intact, genetically perturbed, and disease-affected synapses. acknowledgement: This project has received funding from the European Research Council (ERC) and European Commission (EC), under the European Union’s Horizon 2020 research and innovation programme (ERC grant agreement No. 692692 and Marie Sklodowska-Curie 708497) and from Fonds zur Förderung der Wissenschaftlichen Forschung (Z 312-B27 Wittgenstein award and DK W1205-B09). We thank Johann Danzl and Ryuichi Shigemoto for critically reading the manuscript; Walter Kaufmann, Daniel Gutl, and Vanessa Zheden for extensive EM training, advice, and experimental assistance; Benjamin Suter for substantial help with light stimulation, ImageJ plugins for analysis, and manuscript editing; Florian Marr and Christina Altmutter for technical support; Eleftheria Kralli-Beller for manuscript editing; Julia König and Paul Wurzinger (Leica Microsystems) for helpful technical discussions; and Taija Makinen for providing the Prox1-CreERT2 mouse line. article_processing_charge: No article_type: original author: - first_name: Carolina full_name: Borges Merjane, Carolina id: 4305C450-F248-11E8-B48F-1D18A9856A87 last_name: Borges Merjane orcid: 0000-0003-0005-401X - first_name: Olena full_name: Kim, Olena id: 3F8ABDDA-F248-11E8-B48F-1D18A9856A87 last_name: Kim - first_name: Peter M full_name: Jonas, Peter M id: 353C1B58-F248-11E8-B48F-1D18A9856A87 last_name: Jonas orcid: 0000-0001-5001-4804 citation: ama: Borges Merjane C, Kim O, Jonas PM. Functional electron microscopy (“Flash and Freeze”) of identified cortical synapses in acute brain slices. Neuron. 2020;105:992-1006. doi:10.1016/j.neuron.2019.12.022 apa: Borges Merjane, C., Kim, O., & Jonas, P. M. (2020). Functional electron microscopy (“Flash and Freeze”) of identified cortical synapses in acute brain slices. Neuron. Elsevier. https://doi.org/10.1016/j.neuron.2019.12.022 chicago: Borges Merjane, Carolina, Olena Kim, and Peter M Jonas. “Functional Electron Microscopy (‘Flash and Freeze’) of Identified Cortical Synapses in Acute Brain Slices.” Neuron. Elsevier, 2020. https://doi.org/10.1016/j.neuron.2019.12.022. ieee: C. Borges Merjane, O. Kim, and P. M. Jonas, “Functional electron microscopy (‘Flash and Freeze’) of identified cortical synapses in acute brain slices,” Neuron, vol. 105. Elsevier, pp. 992–1006, 2020. ista: Borges Merjane C, Kim O, Jonas PM. 2020. Functional electron microscopy (“Flash and Freeze”) of identified cortical synapses in acute brain slices. Neuron. 105, 992–1006. mla: Borges Merjane, Carolina, et al. “Functional Electron Microscopy (‘Flash and Freeze’) of Identified Cortical Synapses in Acute Brain Slices.” Neuron, vol. 105, Elsevier, 2020, pp. 992–1006, doi:10.1016/j.neuron.2019.12.022. short: C. Borges Merjane, O. Kim, P.M. Jonas, Neuron 105 (2020) 992–1006. date_created: 2020-02-10T15:59:45Z date_published: 2020-03-18T00:00:00Z date_updated: 2024-03-27T23:30:07Z day: '18' ddc: - '570' department: - _id: PeJo doi: 10.1016/j.neuron.2019.12.022 ec_funded: 1 external_id: isi: - '000520854700008' pmid: - '31928842' file: - access_level: open_access checksum: 3582664addf26859e86ac5bec3e01416 content_type: application/pdf creator: dernst date_created: 2020-11-20T08:58:53Z date_updated: 2020-11-20T08:58:53Z file_id: '8778' file_name: 2020_Neuron_BorgesMerjane.pdf file_size: 9712957 relation: main_file success: 1 file_date_updated: 2020-11-20T08:58:53Z has_accepted_license: '1' intvolume: ' 105' isi: 1 language: - iso: eng month: '03' oa: 1 oa_version: Published Version page: 992-1006 pmid: 1 project: - _id: 25B7EB9E-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '692692' name: Biophysics and circuit function of a giant cortical glumatergic synapse - _id: 25BAF7B2-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '708497' name: Presynaptic calcium channels distribution and impact on coupling at the hippocampal mossy fiber synapse - _id: 25C5A090-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: Z00312 name: The Wittgenstein Prize - _id: 25C3DBB6-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: W01205 name: Zellkommunikation in Gesundheit und Krankheit publication: Neuron publication_identifier: issn: - 0896-6273 publication_status: published publisher: Elsevier quality_controlled: '1' related_material: link: - description: News on IST Homepage relation: press_release url: https://ist.ac.at/en/news/flash-and-freeze-reveals-dynamics-of-nerve-connections/ record: - id: '11196' relation: dissertation_contains status: public scopus_import: '1' status: public title: Functional electron microscopy (“Flash and Freeze”) of identified cortical synapses in acute brain slices tmp: image: /images/cc_by_nc_nd.png legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) short: CC BY-NC-ND (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 105 year: '2020' ... --- _id: '7405' abstract: - lang: eng text: Biophysical modeling of neuronal networks helps to integrate and interpret rapidly growing and disparate experimental datasets at multiple scales. The NetPyNE tool (www.netpyne.org) provides both programmatic and graphical interfaces to develop data-driven multiscale network models in NEURON. NetPyNE clearly separates model parameters from implementation code. Users provide specifications at a high level via a standardized declarative language, for example connectivity rules, to create millions of cell-to-cell connections. NetPyNE then enables users to generate the NEURON network, run efficiently parallelized simulations, optimize and explore network parameters through automated batch runs, and use built-in functions for visualization and analysis – connectivity matrices, voltage traces, spike raster plots, local field potentials, and information theoretic measures. NetPyNE also facilitates model sharing by exporting and importing standardized formats (NeuroML and SONATA). NetPyNE is already being used to teach computational neuroscience students and by modelers to investigate brain regions and phenomena. article_number: e44494 article_processing_charge: No article_type: original author: - first_name: Salvador full_name: Dura-Bernal, Salvador last_name: Dura-Bernal - first_name: Benjamin full_name: Suter, Benjamin id: 4952F31E-F248-11E8-B48F-1D18A9856A87 last_name: Suter orcid: 0000-0002-9885-6936 - first_name: Padraig full_name: Gleeson, Padraig last_name: Gleeson - first_name: Matteo full_name: Cantarelli, Matteo last_name: Cantarelli - first_name: Adrian full_name: Quintana, Adrian last_name: Quintana - first_name: Facundo full_name: Rodriguez, Facundo last_name: Rodriguez - first_name: David J full_name: Kedziora, David J last_name: Kedziora - first_name: George L full_name: Chadderdon, George L last_name: Chadderdon - first_name: Cliff C full_name: Kerr, Cliff C last_name: Kerr - first_name: Samuel A full_name: Neymotin, Samuel A last_name: Neymotin - first_name: Robert A full_name: McDougal, Robert A last_name: McDougal - first_name: Michael full_name: Hines, Michael last_name: Hines - first_name: Gordon MG full_name: Shepherd, Gordon MG last_name: Shepherd - first_name: William W full_name: Lytton, William W last_name: Lytton citation: ama: Dura-Bernal S, Suter B, Gleeson P, et al. NetPyNE, a tool for data-driven multiscale modeling of brain circuits. eLife. 2019;8. doi:10.7554/elife.44494 apa: Dura-Bernal, S., Suter, B., Gleeson, P., Cantarelli, M., Quintana, A., Rodriguez, F., … Lytton, W. W. (2019). NetPyNE, a tool for data-driven multiscale modeling of brain circuits. ELife. eLife Sciences Publications. https://doi.org/10.7554/elife.44494 chicago: Dura-Bernal, Salvador, Benjamin Suter, Padraig Gleeson, Matteo Cantarelli, Adrian Quintana, Facundo Rodriguez, David J Kedziora, et al. “NetPyNE, a Tool for Data-Driven Multiscale Modeling of Brain Circuits.” ELife. eLife Sciences Publications, 2019. https://doi.org/10.7554/elife.44494. ieee: S. Dura-Bernal et al., “NetPyNE, a tool for data-driven multiscale modeling of brain circuits,” eLife, vol. 8. eLife Sciences Publications, 2019. ista: Dura-Bernal S, Suter B, Gleeson P, Cantarelli M, Quintana A, Rodriguez F, Kedziora DJ, Chadderdon GL, Kerr CC, Neymotin SA, McDougal RA, Hines M, Shepherd GM, Lytton WW. 2019. NetPyNE, a tool for data-driven multiscale modeling of brain circuits. eLife. 8, e44494. mla: Dura-Bernal, Salvador, et al. “NetPyNE, a Tool for Data-Driven Multiscale Modeling of Brain Circuits.” ELife, vol. 8, e44494, eLife Sciences Publications, 2019, doi:10.7554/elife.44494. short: S. Dura-Bernal, B. Suter, P. Gleeson, M. Cantarelli, A. Quintana, F. Rodriguez, D.J. Kedziora, G.L. Chadderdon, C.C. Kerr, S.A. Neymotin, R.A. McDougal, M. Hines, G.M. Shepherd, W.W. Lytton, ELife 8 (2019). date_created: 2020-01-30T09:08:01Z date_published: 2019-05-31T00:00:00Z date_updated: 2023-09-07T14:27:52Z day: '31' ddc: - '570' department: - _id: PeJo doi: 10.7554/elife.44494 external_id: isi: - '000468968400001' pmid: - '31025934' file: - access_level: open_access checksum: 7014189c11c10a12feeeae37f054871d content_type: application/pdf creator: dernst date_created: 2020-02-04T08:41:47Z date_updated: 2020-07-14T12:47:57Z file_id: '7444' file_name: 2019_eLife_DuraBernal.pdf file_size: 6182359 relation: main_file file_date_updated: 2020-07-14T12:47:57Z has_accepted_license: '1' intvolume: ' 8' isi: 1 language: - iso: eng month: '05' oa: 1 oa_version: Published Version pmid: 1 publication: eLife publication_identifier: issn: - 2050-084X publication_status: published publisher: eLife Sciences Publications quality_controlled: '1' scopus_import: '1' status: public title: NetPyNE, a tool for data-driven multiscale modeling of brain circuits tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 8 year: '2019' ... --- _id: '11222' acknowledgement: This work was supported by the ERC and EU Horizon 2020 (ERC 692692; MSC-IF 708497) and FWF Z 312-B27 Wittgenstein award; W 1205-B09). article_number: A3.27 article_processing_charge: No author: - first_name: Olena full_name: Kim, Olena id: 3F8ABDDA-F248-11E8-B48F-1D18A9856A87 last_name: Kim - first_name: Carolina full_name: Borges Merjane, Carolina id: 4305C450-F248-11E8-B48F-1D18A9856A87 last_name: Borges Merjane orcid: 0000-0003-0005-401X - first_name: Peter M full_name: Jonas, Peter M id: 353C1B58-F248-11E8-B48F-1D18A9856A87 last_name: Jonas orcid: 0000-0001-5001-4804 citation: ama: 'Kim O, Borges Merjane C, Jonas PM. Functional analysis of the docked vesicle pool in hippocampal mossy fiber terminals by electron microscopy. In: Intrinsic Activity. Vol 7. Austrian Pharmacological Society; 2019. doi:10.25006/ia.7.s1-a3.27' apa: 'Kim, O., Borges Merjane, C., & Jonas, P. M. (2019). Functional analysis of the docked vesicle pool in hippocampal mossy fiber terminals by electron microscopy. In Intrinsic Activity (Vol. 7). Innsbruck, Austria: Austrian Pharmacological Society. https://doi.org/10.25006/ia.7.s1-a3.27' chicago: Kim, Olena, Carolina Borges Merjane, and Peter M Jonas. “Functional Analysis of the Docked Vesicle Pool in Hippocampal Mossy Fiber Terminals by Electron Microscopy.” In Intrinsic Activity, Vol. 7. Austrian Pharmacological Society, 2019. https://doi.org/10.25006/ia.7.s1-a3.27. ieee: O. Kim, C. Borges Merjane, and P. M. Jonas, “Functional analysis of the docked vesicle pool in hippocampal mossy fiber terminals by electron microscopy,” in Intrinsic Activity, Innsbruck, Austria, 2019, vol. 7, no. Suppl. 1. ista: 'Kim O, Borges Merjane C, Jonas PM. 2019. Functional analysis of the docked vesicle pool in hippocampal mossy fiber terminals by electron microscopy. Intrinsic Activity. ANA: Austrian Neuroscience Association ; APHAR: Austrian Pharmacological Society vol. 7, A3.27.' mla: Kim, Olena, et al. “Functional Analysis of the Docked Vesicle Pool in Hippocampal Mossy Fiber Terminals by Electron Microscopy.” Intrinsic Activity, vol. 7, no. Suppl. 1, A3.27, Austrian Pharmacological Society, 2019, doi:10.25006/ia.7.s1-a3.27. short: O. Kim, C. Borges Merjane, P.M. Jonas, in:, Intrinsic Activity, Austrian Pharmacological Society, 2019. conference: end_date: 2019-09-27 location: Innsbruck, Austria name: 'ANA: Austrian Neuroscience Association ; APHAR: Austrian Pharmacological Society' start_date: 2019-09-25 date_created: 2022-04-20T15:06:05Z date_published: 2019-09-11T00:00:00Z date_updated: 2024-03-27T23:30:07Z day: '11' department: - _id: PeJo doi: 10.25006/ia.7.s1-a3.27 ec_funded: 1 intvolume: ' 7' issue: Suppl. 1 keyword: - hippocampus - mossy fibers - readily releasable pool - electron microscopy language: - iso: eng main_file_link: - open_access: '1' url: https://www.intrinsicactivity.org/2019/7/S1/A3.27/ month: '09' oa: 1 oa_version: Published Version project: - _id: 25B7EB9E-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '692692' name: Biophysics and circuit function of a giant cortical glumatergic synapse - _id: 25BAF7B2-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '708497' name: Presynaptic calcium channels distribution and impact on coupling at the hippocampal mossy fiber synapse - _id: 25C3DBB6-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: W01205 name: Zellkommunikation in Gesundheit und Krankheit - _id: 25C5A090-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: Z00312 name: The Wittgenstein Prize publication: Intrinsic Activity publication_identifier: issn: - 2309-8503 publication_status: published publisher: Austrian Pharmacological Society quality_controlled: '1' related_material: record: - id: '11196' relation: dissertation_contains status: public status: public title: Functional analysis of the docked vesicle pool in hippocampal mossy fiber terminals by electron microscopy type: conference_abstract user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9 volume: 7 year: '2019' ... --- _id: '6363' abstract: - lang: eng text: "Distinguishing between similar experiences is achieved by the brain \ in a process called pattern separation. In the hippocampus, pattern \ separation reduces the interference of memories and increases the storage capacity by decorrelating similar inputs patterns of neuronal activity into \ non-overlapping output firing patterns. Winners-take-all (WTA) mechanism \ is a theoretical model for pattern separation in which a \"winner\" \ cell suppresses the activity of the neighboring neurons through feedback inhibition. However, if the network properties of the dentate gyrus support WTA as a biologically conceivable model remains unknown. Here, we showed that the connectivity rules of PV+interneurons and their synaptic properties are optimizedfor efficient pattern separation. We found using multiple whole-cell in vitrorecordings that PV+interneurons mainly connect to granule cells (GC) through lateral inhibition, a form of feedback inhibition in which a GC inhibits other GCs but not \ itself through the activation of PV+interneurons. Thus, lateral inhibition between GC–PV+interneurons was ~10 times more abundant than recurrent connections. Furthermore, the GC–PV+interneuron connectivity was more spatially confined \ but less abundant than PV+interneurons–GC connectivity, leading to an \ asymmetrical distribution of excitatory and inhibitory connectivity. Our network model of the dentate gyrus with incorporated real connectivity rules efficiently decorrelates neuronal activity patterns using WTA as the primary mechanism. \ This process relied on lateral inhibition, fast-signaling properties of \ PV+interneurons and the asymmetrical distribution of excitatory and inhibitory connectivity. Finally, we found that silencing the activity of PV+interneurons in vivoleads to acute deficits in discrimination between similar environments, suggesting that PV+interneuron networks are necessary for behavioral relevant computations. Our results demonstrate that PV+interneurons possess unique connectivity and fast signaling properties that confer to the dentate \ gyrus network properties that allow the emergence of pattern separation. Thus, our results contribute to the knowledge of how specific forms of network organization underlie sophisticated types of information processing. \r\n" alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: 'Claudia ' full_name: 'Espinoza Martinez, Claudia ' id: 31FFEE2E-F248-11E8-B48F-1D18A9856A87 last_name: Espinoza Martinez orcid: 0000-0003-4710-2082 citation: ama: Espinoza Martinez C. Parvalbumin+ interneurons enable efficient pattern separation in hippocampal microcircuits. 2019. doi:10.15479/AT:ISTA:6363 apa: Espinoza Martinez, C. (2019). Parvalbumin+ interneurons enable efficient pattern separation in hippocampal microcircuits. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:6363 chicago: Espinoza Martinez, Claudia . “Parvalbumin+ Interneurons Enable Efficient Pattern Separation in Hippocampal Microcircuits.” Institute of Science and Technology Austria, 2019. https://doi.org/10.15479/AT:ISTA:6363. ieee: C. Espinoza Martinez, “Parvalbumin+ interneurons enable efficient pattern separation in hippocampal microcircuits,” Institute of Science and Technology Austria, 2019. ista: Espinoza Martinez C. 2019. Parvalbumin+ interneurons enable efficient pattern separation in hippocampal microcircuits. Institute of Science and Technology Austria. mla: Espinoza Martinez, Claudia. Parvalbumin+ Interneurons Enable Efficient Pattern Separation in Hippocampal Microcircuits. Institute of Science and Technology Austria, 2019, doi:10.15479/AT:ISTA:6363. short: C. Espinoza Martinez, Parvalbumin+ Interneurons Enable Efficient Pattern Separation in Hippocampal Microcircuits, Institute of Science and Technology Austria, 2019. date_created: 2019-04-30T11:56:10Z date_published: 2019-04-30T00:00:00Z date_updated: 2023-09-15T12:03:48Z day: '30' ddc: - '570' degree_awarded: PhD department: - _id: PeJo doi: 10.15479/AT:ISTA:6363 file: - access_level: open_access checksum: 77c6c05cfe8b58c8abcf1b854375d084 content_type: application/pdf creator: cespinoza date_created: 2019-05-07T16:00:39Z date_updated: 2021-02-11T11:17:15Z embargo: 2020-05-09 file_id: '6389' file_name: Espinozathesis_all2.pdf file_size: 13966891 relation: main_file - access_level: closed checksum: f6aa819f127691a2b0fc21c76eb09746 content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: cespinoza date_created: 2019-05-07T16:00:48Z date_updated: 2020-07-14T12:47:28Z embargo_to: open_access file_id: '6390' file_name: Espinoza_Thesis.docx file_size: 11159900 relation: source_file file_date_updated: 2021-02-11T11:17:15Z has_accepted_license: '1' language: - iso: eng month: '04' oa: 1 oa_version: Published Version page: '140' publication_identifier: isbn: - 978-3-99078-000-8 issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '21' relation: part_of_dissertation status: public status: public supervisor: - first_name: Peter M full_name: Jonas, Peter M id: 353C1B58-F248-11E8-B48F-1D18A9856A87 last_name: Jonas orcid: 0000-0001-5001-4804 title: Parvalbumin+ interneurons enable efficient pattern separation in hippocampal microcircuits type: dissertation user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2019' ... --- _id: '320' abstract: - lang: eng text: 'Fast-spiking, parvalbumin-expressing GABAergic interneurons (PV+-BCs) express a complex machinery of rapid signaling mechanisms, including specialized voltage-gated ion channels to generate brief action potentials (APs). However, short APs are associated with overlapping Na+ and K+ fluxes and are therefore energetically expensive. How the potentially vicious combination of high AP frequency and inefficient spike generation can be reconciled with limited energy supply is presently unclear. To address this question, we performed direct recordings from the PV+-BC axon, the subcellular structure where active conductances for AP initiation and propagation are located. Surprisingly, the energy required for the AP was, on average, only ∼1.6 times the theoretical minimum. High energy efficiency emerged from the combination of fast inactivation of Na+ channels and delayed activation of Kv3-type K+ channels, which minimized ion flux overlap during APs. Thus, the complementary tuning of axonal Na+ and K+ channel gating optimizes both fast signaling properties and metabolic efficiency. Hu et al. demonstrate that action potentials in parvalbumin-expressing GABAergic interneuron axons are energetically efficient, which is highly unexpected given their brief duration. High energy efficiency emerges from the combination of fast inactivation of voltage-gated Na+ channels and delayed activation of Kv3 channels in the axon. ' article_processing_charge: Yes (in subscription journal) author: - first_name: Hua full_name: Hu, Hua id: 4AC0145C-F248-11E8-B48F-1D18A9856A87 last_name: Hu - first_name: Fabian full_name: Roth, Fabian last_name: Roth - first_name: David H full_name: Vandael, David H id: 3AE48E0A-F248-11E8-B48F-1D18A9856A87 last_name: Vandael orcid: 0000-0001-7577-1676 - first_name: Peter M full_name: Jonas, Peter M id: 353C1B58-F248-11E8-B48F-1D18A9856A87 last_name: Jonas orcid: 0000-0001-5001-4804 citation: ama: Hu H, Roth F, Vandael DH, Jonas PM. Complementary tuning of Na+ and K+ channel gating underlies fast and energy-efficient action potentials in GABAergic interneuron axons. Neuron. 2018;98(1):156-165. doi:10.1016/j.neuron.2018.02.024 apa: Hu, H., Roth, F., Vandael, D. H., & Jonas, P. M. (2018). Complementary tuning of Na+ and K+ channel gating underlies fast and energy-efficient action potentials in GABAergic interneuron axons. Neuron. Elsevier. https://doi.org/10.1016/j.neuron.2018.02.024 chicago: Hu, Hua, Fabian Roth, David H Vandael, and Peter M Jonas. “Complementary Tuning of Na+ and K+ Channel Gating Underlies Fast and Energy-Efficient Action Potentials in GABAergic Interneuron Axons.” Neuron. Elsevier, 2018. https://doi.org/10.1016/j.neuron.2018.02.024. ieee: H. Hu, F. Roth, D. H. Vandael, and P. M. Jonas, “Complementary tuning of Na+ and K+ channel gating underlies fast and energy-efficient action potentials in GABAergic interneuron axons,” Neuron, vol. 98, no. 1. Elsevier, pp. 156–165, 2018. ista: Hu H, Roth F, Vandael DH, Jonas PM. 2018. Complementary tuning of Na+ and K+ channel gating underlies fast and energy-efficient action potentials in GABAergic interneuron axons. Neuron. 98(1), 156–165. mla: Hu, Hua, et al. “Complementary Tuning of Na+ and K+ Channel Gating Underlies Fast and Energy-Efficient Action Potentials in GABAergic Interneuron Axons.” Neuron, vol. 98, no. 1, Elsevier, 2018, pp. 156–65, doi:10.1016/j.neuron.2018.02.024. short: H. Hu, F. Roth, D.H. Vandael, P.M. Jonas, Neuron 98 (2018) 156–165. date_created: 2018-12-11T11:45:48Z date_published: 2018-04-04T00:00:00Z date_updated: 2023-09-11T12:45:10Z day: '04' ddc: - '570' department: - _id: PeJo doi: 10.1016/j.neuron.2018.02.024 ec_funded: 1 external_id: isi: - '000429192100016' file: - access_level: open_access checksum: 76070f3729f9c603e1080d0151aa2b11 content_type: application/pdf creator: dernst date_created: 2018-12-17T10:37:50Z date_updated: 2020-07-14T12:46:03Z file_id: '5690' file_name: 2018_Neuron_Hu.pdf file_size: 3180444 relation: main_file file_date_updated: 2020-07-14T12:46:03Z has_accepted_license: '1' intvolume: ' 98' isi: 1 issue: '1' language: - iso: eng month: '04' oa: 1 oa_version: Published Version page: 156 - 165 project: - _id: 25C0F108-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '268548' name: Nanophysiology of fast-spiking, parvalbumin-expressing GABAergic interneurons - _id: 25B7EB9E-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '692692' name: Biophysics and circuit function of a giant cortical glumatergic synapse - _id: 25C26B1E-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: P24909-B24 name: Mechanisms of transmitter release at GABAergic synapses - _id: 25C5A090-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: Z00312 name: The Wittgenstein Prize publication: Neuron publication_status: published publisher: Elsevier publist_id: '7545' quality_controlled: '1' related_material: link: - description: News on IST Homepage relation: press_release url: https://ist.ac.at/en/news/a-certain-type-of-neurons-is-more-energy-efficient-than-previously-assumed/ scopus_import: '1' status: public title: Complementary tuning of Na+ and K+ channel gating underlies fast and energy-efficient action potentials in GABAergic interneuron axons tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 98 year: '2018' ... --- _id: '324' abstract: - lang: eng text: Neuronal networks in the brain consist of two main types of neuron, glutamatergic principal neurons and GABAergic interneurons. Although these interneurons only represent 10–20% of the whole population, they mediate feedback and feedforward inhibition and are involved in the generation of high-frequency network oscillations. A hallmark functional property of GABAergic interneurons, especially of the parvalbumin‑expressing (PV+) subtypes, is the speed of signaling at their output synapse across species and brain regions. Several molecular and subcellular factors may underlie the submillisecond signaling at GABAergic synapses. Such as the selective use of P/Q type Ca2+ channels and the tight coupling between Ca2+ channels and Ca2+ sensors of exocytosis. However, whether the molecular identity of the release sensor contributes to these signaling properties remains unclear. Besides, these interneurons are mainly show depression in response to train of stimuli. How could they keep sufficient release to control the activity of postsynaptic principal neurons during high network activity, is largely elusive. For my Ph.D. work, we firstly examined the Ca2+ sensor of exocytosis at the GABAergic basket cell (BC) to Purkinje cell (PC) synapse in the cerebellum. Immunolabeling suggested that BC terminals selectively expressed synaptotagmin 2 (Syt2), whereas synaptotagmin 1 (Syt1) was enriched in excitatory terminals. Genetic elimination of Syt2 reduced action potential-evoked release to ~10% compared to the wild-type control, identifying Syt2 as the major Ca2+ sensor at BC‑PC synapses. Differential adenovirus-mediated rescue revealed Syt2 triggered release with shorter latency and higher temporal precision, and mediated faster vesicle pool replenishment than Syt1. Furthermore, deletion of Syt2 severely reduced and delayed disynaptic inhibition following parallel fiber stimulation. Thus, the selective use of Syt2 as the release sensor at BC–PC synapse ensures fast feedforward inhibition in cerebellar microcircuits. Additionally, we tested the function of another synaptotagmin member, Syt7, for inhibitory synaptic transmission at the BC–PC synapse. Syt7 is thought to be a Ca2+ sensor that mediates asynchronous transmitter release and facilitation at synapses. However, it is strongly expressed in fast-spiking, PV+ GABAergic interneurons and the output synapses of these neurons produce only minimal asynchronous release and show depression rather than facilitation. How could Syt7, a facilitation sensor, contribute to the depressed inhibitory synaptic transmission needs to be further investigated and understood. Our results indicated that at the BC–PC synapse, Syt7 contributes to asynchronous release, pool replenishment and facilitation. In combination, these three effects ensure efficient transmitter release during high‑frequency activity and guarantee frequency independence of inhibition. Taken together, our results confirmed that Syt2, which has the fastest kinetic properties among all synaptotagmin members, is mainly used by the inhibitory BC‑PC synapse for synaptic transmission, contributing to the speed and temporal precision of transmitter release. Furthermore, we showed that Syt7, another highly expressed synaptotagmin member in the output synapses of cerebellar BCs, is used for ensuring efficient inhibitor synaptic transmission during high activity. alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Chong full_name: Chen, Chong id: 3DFD581A-F248-11E8-B48F-1D18A9856A87 last_name: Chen citation: ama: Chen C. Synaptotagmins ensure speed and efficiency of inhibitory neurotransmitter release. 2018. doi:10.15479/AT:ISTA:th_997 apa: Chen, C. (2018). Synaptotagmins ensure speed and efficiency of inhibitory neurotransmitter release. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:th_997 chicago: Chen, Chong. “Synaptotagmins Ensure Speed and Efficiency of Inhibitory Neurotransmitter Release.” Institute of Science and Technology Austria, 2018. https://doi.org/10.15479/AT:ISTA:th_997. ieee: C. Chen, “Synaptotagmins ensure speed and efficiency of inhibitory neurotransmitter release,” Institute of Science and Technology Austria, 2018. ista: Chen C. 2018. Synaptotagmins ensure speed and efficiency of inhibitory neurotransmitter release. Institute of Science and Technology Austria. mla: Chen, Chong. Synaptotagmins Ensure Speed and Efficiency of Inhibitory Neurotransmitter Release. Institute of Science and Technology Austria, 2018, doi:10.15479/AT:ISTA:th_997. short: C. Chen, Synaptotagmins Ensure Speed and Efficiency of Inhibitory Neurotransmitter Release, Institute of Science and Technology Austria, 2018. date_created: 2018-12-11T11:45:49Z date_published: 2018-03-01T00:00:00Z date_updated: 2023-09-27T12:26:03Z day: '01' ddc: - '571' degree_awarded: PhD department: - _id: PeJo doi: 10.15479/AT:ISTA:th_997 file: - access_level: open_access checksum: 8e163ae9e927401b9fa7c1b3e6a3631a content_type: application/pdf creator: system date_created: 2018-12-12T10:13:58Z date_updated: 2020-07-14T12:46:04Z file_id: '5046' file_name: IST-2018-997-v1+1_Thesis_chong_a.pdf file_size: 8719458 relation: main_file - access_level: closed checksum: f7d7260029a5fbb5c982db61328ade52 content_type: application/octet-stream creator: dernst date_created: 2019-04-05T09:25:26Z date_updated: 2020-07-14T12:46:04Z file_id: '6221' file_name: 2018_Thesis_chong_source.pages file_size: 47841940 relation: source_file file_date_updated: 2020-07-14T12:46:04Z has_accepted_license: '1' language: - iso: eng month: '03' oa: 1 oa_version: Published Version page: '110' publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria publist_id: '7541' pubrep_id: '997' related_material: record: - id: '1117' relation: part_of_dissertation status: public - id: '749' relation: part_of_dissertation status: public status: public supervisor: - first_name: Peter M full_name: Jonas, Peter M id: 353C1B58-F248-11E8-B48F-1D18A9856A87 last_name: Jonas orcid: 0000-0001-5001-4804 title: Synaptotagmins ensure speed and efficiency of inhibitory neurotransmitter release tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: dissertation user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2018' ... --- _id: '21' abstract: - lang: eng text: Parvalbumin-positive (PV+) GABAergic interneurons in hippocampal microcircuits are thought to play a key role in several higher network functions, such as feedforward and feedback inhibition, network oscillations, and pattern separation. Fast lateral inhibition mediated by GABAergic interneurons may implement a winner-takes-all mechanism in the hippocampal input layer. However, it is not clear whether the functional connectivity rules of granule cells (GCs) and interneurons in the dentate gyrus are consistent with such a mechanism. Using simultaneous patch-clamp recordings from up to seven GCs and up to four PV+ interneurons in the dentate gyrus, we find that connectivity is structured in space, synapse-specific, and enriched in specific disynaptic motifs. In contrast to the neocortex, lateral inhibition in the dentate gyrus (in which a GC inhibits neighboring GCs via a PV+ interneuron) is ~ 10-times more abundant than recurrent inhibition (in which a GC inhibits itself). Thus, unique connectivity rules may enable the dentate gyrus to perform specific higher-order computations acknowledgement: This project received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No 692692) and the Fond zur Förderung der Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein award), both to P.J.. article_number: '4605' article_processing_charge: No article_type: original author: - first_name: 'Claudia ' full_name: 'Espinoza Martinez, Claudia ' id: 31FFEE2E-F248-11E8-B48F-1D18A9856A87 last_name: Espinoza Martinez orcid: 0000-0003-4710-2082 - first_name: José full_name: Guzmán, José id: 30CC5506-F248-11E8-B48F-1D18A9856A87 last_name: Guzmán orcid: 0000-0003-2209-5242 - first_name: Xiaomin full_name: Zhang, Xiaomin id: 423EC9C2-F248-11E8-B48F-1D18A9856A87 last_name: Zhang - first_name: Peter M full_name: Jonas, Peter M id: 353C1B58-F248-11E8-B48F-1D18A9856A87 last_name: Jonas orcid: 0000-0001-5001-4804 citation: ama: Espinoza Martinez C, Guzmán J, Zhang X, Jonas PM. Parvalbumin+ interneurons obey unique connectivity rules and establish a powerful lateral-inhibition microcircuit in dentate gyrus. Nature Communications. 2018;9(1). doi:10.1038/s41467-018-06899-3 apa: Espinoza Martinez, C., Guzmán, J., Zhang, X., & Jonas, P. M. (2018). Parvalbumin+ interneurons obey unique connectivity rules and establish a powerful lateral-inhibition microcircuit in dentate gyrus. Nature Communications. Nature Publishing Group. https://doi.org/10.1038/s41467-018-06899-3 chicago: Espinoza Martinez, Claudia , José Guzmán, Xiaomin Zhang, and Peter M Jonas. “Parvalbumin+ Interneurons Obey Unique Connectivity Rules and Establish a Powerful Lateral-Inhibition Microcircuit in Dentate Gyrus.” Nature Communications. Nature Publishing Group, 2018. https://doi.org/10.1038/s41467-018-06899-3. ieee: C. Espinoza Martinez, J. Guzmán, X. Zhang, and P. M. Jonas, “Parvalbumin+ interneurons obey unique connectivity rules and establish a powerful lateral-inhibition microcircuit in dentate gyrus,” Nature Communications, vol. 9, no. 1. Nature Publishing Group, 2018. ista: Espinoza Martinez C, Guzmán J, Zhang X, Jonas PM. 2018. Parvalbumin+ interneurons obey unique connectivity rules and establish a powerful lateral-inhibition microcircuit in dentate gyrus. Nature Communications. 9(1), 4605. mla: Espinoza Martinez, Claudia, et al. “Parvalbumin+ Interneurons Obey Unique Connectivity Rules and Establish a Powerful Lateral-Inhibition Microcircuit in Dentate Gyrus.” Nature Communications, vol. 9, no. 1, 4605, Nature Publishing Group, 2018, doi:10.1038/s41467-018-06899-3. short: C. Espinoza Martinez, J. Guzmán, X. Zhang, P.M. Jonas, Nature Communications 9 (2018). date_created: 2018-12-11T11:44:12Z date_published: 2018-11-02T00:00:00Z date_updated: 2024-03-27T23:30:31Z day: '02' ddc: - '570' department: - _id: PeJo doi: 10.1038/s41467-018-06899-3 ec_funded: 1 external_id: isi: - '000449069700009' file: - access_level: open_access checksum: 9fe2a63bd95a5067d896c087d07998f3 content_type: application/pdf creator: dernst date_created: 2018-12-17T15:41:57Z date_updated: 2020-07-14T12:45:28Z file_id: '5715' file_name: 2018_NatureComm_Espinoza.pdf file_size: 4651930 relation: main_file file_date_updated: 2020-07-14T12:45:28Z has_accepted_license: '1' intvolume: ' 9' isi: 1 issue: '1' language: - iso: eng month: '11' oa: 1 oa_version: Published Version project: - _id: 25B7EB9E-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '692692' name: Biophysics and circuit function of a giant cortical glumatergic synapse - _id: 25C5A090-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: Z00312 name: The Wittgenstein Prize publication: Nature Communications publication_status: published publisher: Nature Publishing Group publist_id: '8034' quality_controlled: '1' related_material: link: - description: News on IST Homepage relation: press_release url: https://ist.ac.at/en/news/lateral-inhibition-keeps-similar-memories-apart/ record: - id: '6363' relation: dissertation_contains status: public scopus_import: '1' status: public title: Parvalbumin+ interneurons obey unique connectivity rules and establish a powerful lateral-inhibition microcircuit in dentate gyrus tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 9 year: '2018' ... --- _id: '630' abstract: - lang: eng text: 'Background: Standards have become available to share semantically encoded vital parameters from medical devices, as required for example by personal healthcare records. Standardised sharing of biosignal data largely remains open. Objectives: The goal of this work is to explore available biosignal file format and data exchange standards and profiles, and to conceptualise end-To-end solutions. Methods: The authors reviewed and discussed available biosignal file format standards with other members of international standards development organisations (SDOs). Results: A raw concept for standards based acquisition, storage, archiving and sharing of biosignals was developed. The GDF format may serve for storing biosignals. Signals can then be shared using FHIR resources and may be stored on FHIR servers or in DICOM archives, with DICOM waveforms as one possible format. Conclusion: Currently a group of international SDOs (e.g. HL7, IHE, DICOM, IEEE) is engaged in intensive discussions. This discussion extends existing work that already was adopted by large implementer communities. The concept presented here only reports the current status of the discussion in Austria. The discussion will continue internationally, with results to be expected over the coming years.' alternative_title: - Studies in Health Technology and Informatics author: - first_name: Stefan full_name: Sauermann, Stefan last_name: Sauermann - first_name: Veronika full_name: David, Veronika last_name: David - first_name: Alois full_name: Schlögl, Alois id: 45BF87EE-F248-11E8-B48F-1D18A9856A87 last_name: Schlögl orcid: 0000-0002-5621-8100 - first_name: Reinhard full_name: Egelkraut, Reinhard last_name: Egelkraut - first_name: Matthias full_name: Frohner, Matthias last_name: Frohner - first_name: Birgit full_name: Pohn, Birgit last_name: Pohn - first_name: Philipp full_name: Urbauer, Philipp last_name: Urbauer - first_name: Alexander full_name: Mense, Alexander last_name: Mense citation: ama: 'Sauermann S, David V, Schlögl A, et al. Biosignals standards and FHIR: The way to go. In: Vol 236. IOS Press; 2017:356-362. doi:10.3233/978-1-61499-759-7-356' apa: 'Sauermann, S., David, V., Schlögl, A., Egelkraut, R., Frohner, M., Pohn, B., … Mense, A. (2017). Biosignals standards and FHIR: The way to go (Vol. 236, pp. 356–362). Presented at the eHealth: Health Informatics Meets eHealth, Vienna, Austria: IOS Press. https://doi.org/10.3233/978-1-61499-759-7-356' chicago: 'Sauermann, Stefan, Veronika David, Alois Schlögl, Reinhard Egelkraut, Matthias Frohner, Birgit Pohn, Philipp Urbauer, and Alexander Mense. “Biosignals Standards and FHIR: The Way to Go,” 236:356–62. IOS Press, 2017. https://doi.org/10.3233/978-1-61499-759-7-356.' ieee: 'S. Sauermann et al., “Biosignals standards and FHIR: The way to go,” presented at the eHealth: Health Informatics Meets eHealth, Vienna, Austria, 2017, vol. 236, pp. 356–362.' ista: 'Sauermann S, David V, Schlögl A, Egelkraut R, Frohner M, Pohn B, Urbauer P, Mense A. 2017. Biosignals standards and FHIR: The way to go. eHealth: Health Informatics Meets eHealth, Studies in Health Technology and Informatics, vol. 236, 356–362.' mla: 'Sauermann, Stefan, et al. Biosignals Standards and FHIR: The Way to Go. Vol. 236, IOS Press, 2017, pp. 356–62, doi:10.3233/978-1-61499-759-7-356.' short: S. Sauermann, V. David, A. Schlögl, R. Egelkraut, M. Frohner, B. Pohn, P. Urbauer, A. Mense, in:, IOS Press, 2017, pp. 356–362. conference: end_date: 2017-05-24 location: Vienna, Austria name: 'eHealth: Health Informatics Meets eHealth' start_date: 2017-05-23 date_created: 2018-12-11T11:47:36Z date_published: 2017-01-01T00:00:00Z date_updated: 2021-01-12T08:06:59Z day: '01' ddc: - '005' department: - _id: ScienComp - _id: PeJo doi: 10.3233/978-1-61499-759-7-356 file: - access_level: open_access checksum: 1254dcc5b04a996d97fad9a726b42727 content_type: application/pdf creator: system date_created: 2018-12-12T10:11:56Z date_updated: 2020-07-14T12:47:27Z file_id: '4913' file_name: IST-2017-906-v1+1_SHTI236-0356.pdf file_size: 443635 relation: main_file file_date_updated: 2020-07-14T12:47:27Z has_accepted_license: '1' intvolume: ' 236' language: - iso: eng license: https://creativecommons.org/licenses/by-nc/4.0/ month: '01' oa: 1 oa_version: Published Version page: 356 - 362 publication_identifier: isbn: - 978-161499758-0 publication_status: published publisher: IOS Press publist_id: '7164' pubrep_id: '906' quality_controlled: '1' scopus_import: 1 status: public title: 'Biosignals standards and FHIR: The way to go' tmp: image: /images/cc_by_nc.png legal_code_url: https://creativecommons.org/licenses/by-nc/4.0/legalcode name: Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) short: CC BY-NC (4.0) type: conference user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 236 year: '2017' ... --- _id: '706' abstract: - lang: eng text: A hippocampal mossy fiber synapse has a complex structure and is implicated in learning and memory. In this synapse, the mossy fiber boutons attach to the dendritic shaft by puncta adherentia junctions and wrap around a multiply-branched spine, forming synaptic junctions. We have recently shown using transmission electron microscopy, immunoelectron microscopy and serial block face-scanning electron microscopy that atypical puncta adherentia junctions are formed in the afadin-deficient mossy fiber synapse and that the complexity of postsynaptic spines and mossy fiber boutons, the number of spine heads, the area of postsynaptic densities and the density of synaptic vesicles docked to active zones are decreased in the afadin-deficient synapse. We investigated here the roles of afadin in the functional differentiations of the mossy fiber synapse using the afadin-deficient mice. The electrophysiological studies showed that both the release probability of glutamate and the postsynaptic responsiveness to glutamate were markedly reduced, but not completely lost, in the afadin-deficient mossy fiber synapse, whereas neither long-term potentiation nor long-term depression was affected. These results indicate that afadin plays roles in the functional differentiations of the presynapse and the postsynapse of the hippocampal mossy fiber synapse. author: - first_name: Xiaoqi full_name: Geng, Xiaoqi id: 3395256A-F248-11E8-B48F-1D18A9856A87 last_name: Geng - first_name: Tomohiko full_name: Maruo, Tomohiko last_name: Maruo - first_name: Kenji full_name: Mandai, Kenji last_name: Mandai - first_name: Irwan full_name: Supriyanto, Irwan last_name: Supriyanto - first_name: Muneaki full_name: Miyata, Muneaki last_name: Miyata - first_name: Shotaro full_name: Sakakibara, Shotaro last_name: Sakakibara - first_name: Akira full_name: Mizoguchi, Akira last_name: Mizoguchi - first_name: Yoshimi full_name: Takai, Yoshimi last_name: Takai - first_name: Masahiro full_name: Mori, Masahiro last_name: Mori citation: ama: Geng X, Maruo T, Mandai K, et al. Roles of afadin in functional differentiations of hippocampal mossy fiber synapse. Genes to Cells. 2017;22(8):715-722. doi:10.1111/gtc.12508 apa: Geng, X., Maruo, T., Mandai, K., Supriyanto, I., Miyata, M., Sakakibara, S., … Mori, M. (2017). Roles of afadin in functional differentiations of hippocampal mossy fiber synapse. Genes to Cells. Wiley-Blackwell. https://doi.org/10.1111/gtc.12508 chicago: Geng, Xiaoqi, Tomohiko Maruo, Kenji Mandai, Irwan Supriyanto, Muneaki Miyata, Shotaro Sakakibara, Akira Mizoguchi, Yoshimi Takai, and Masahiro Mori. “Roles of Afadin in Functional Differentiations of Hippocampal Mossy Fiber Synapse.” Genes to Cells. Wiley-Blackwell, 2017. https://doi.org/10.1111/gtc.12508. ieee: X. Geng et al., “Roles of afadin in functional differentiations of hippocampal mossy fiber synapse,” Genes to Cells, vol. 22, no. 8. Wiley-Blackwell, pp. 715–722, 2017. ista: Geng X, Maruo T, Mandai K, Supriyanto I, Miyata M, Sakakibara S, Mizoguchi A, Takai Y, Mori M. 2017. Roles of afadin in functional differentiations of hippocampal mossy fiber synapse. Genes to Cells. 22(8), 715–722. mla: Geng, Xiaoqi, et al. “Roles of Afadin in Functional Differentiations of Hippocampal Mossy Fiber Synapse.” Genes to Cells, vol. 22, no. 8, Wiley-Blackwell, 2017, pp. 715–22, doi:10.1111/gtc.12508. short: X. Geng, T. Maruo, K. Mandai, I. Supriyanto, M. Miyata, S. Sakakibara, A. Mizoguchi, Y. Takai, M. Mori, Genes to Cells 22 (2017) 715–722. date_created: 2018-12-11T11:48:02Z date_published: 2017-08-01T00:00:00Z date_updated: 2021-01-12T08:11:37Z day: '01' department: - _id: PeJo doi: 10.1111/gtc.12508 intvolume: ' 22' issue: '8' language: - iso: eng month: '08' oa_version: None page: 715 - 722 publication: Genes to Cells publication_identifier: issn: - '13569597' publication_status: published publisher: Wiley-Blackwell publist_id: '6987' quality_controlled: '1' scopus_import: 1 status: public title: Roles of afadin in functional differentiations of hippocampal mossy fiber synapse type: journal_article user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87 volume: 22 year: '2017' ... --- _id: '1118' abstract: - lang: eng text: Sharp wave-ripple (SWR) oscillations play a key role in memory consolidation during non-rapid eye movement sleep, immobility, and consummatory behavior. However, whether temporally modulated synaptic excitation or inhibition underlies the ripples is controversial. To address this question, we performed simultaneous recordings of excitatory and inhibitory postsynaptic currents (EPSCs and IPSCs) and local field potentials (LFPs) in the CA1 region of awake mice in vivo. During SWRs, inhibition dominated over excitation, with a peak conductance ratio of 4.1 ± 0.5. Furthermore, the amplitude of SWR-associated IPSCs was positively correlated with SWR magnitude, whereas that of EPSCs was not. Finally, phase analysis indicated that IPSCs were phase-locked to individual ripple cycles, whereas EPSCs were uniformly distributed in phase space. Optogenetic inhibition indicated that PV+ interneurons provided a major contribution to SWR-associated IPSCs. Thus, phasic inhibition, but not excitation, shapes SWR oscillations in the hippocampal CA1 region in vivo. acknowledged_ssus: - _id: M-Shop - _id: ScienComp - _id: PreCl article_processing_charge: No author: - first_name: Jian full_name: Gan, Jian id: 3614E438-F248-11E8-B48F-1D18A9856A87 last_name: Gan - first_name: Shih-Ming full_name: Weng, Shih-Ming id: 2F9C5AC8-F248-11E8-B48F-1D18A9856A87 last_name: Weng - first_name: Alejandro full_name: Pernia-Andrade, Alejandro id: 36963E98-F248-11E8-B48F-1D18A9856A87 last_name: Pernia-Andrade - first_name: Jozsef L full_name: Csicsvari, Jozsef L id: 3FA14672-F248-11E8-B48F-1D18A9856A87 last_name: Csicsvari orcid: 0000-0002-5193-4036 - first_name: Peter M full_name: Jonas, Peter M id: 353C1B58-F248-11E8-B48F-1D18A9856A87 last_name: Jonas orcid: 0000-0001-5001-4804 citation: ama: Gan J, Weng S-M, Pernia-Andrade A, Csicsvari JL, Jonas PM. Phase-locked inhibition, but not excitation, underlies hippocampal ripple oscillations in awake mice in vivo. Neuron. 2017;93(2):308-314. doi:10.1016/j.neuron.2016.12.018 apa: Gan, J., Weng, S.-M., Pernia-Andrade, A., Csicsvari, J. L., & Jonas, P. M. (2017). Phase-locked inhibition, but not excitation, underlies hippocampal ripple oscillations in awake mice in vivo. Neuron. Elsevier. https://doi.org/10.1016/j.neuron.2016.12.018 chicago: Gan, Jian, Shih-Ming Weng, Alejandro Pernia-Andrade, Jozsef L Csicsvari, and Peter M Jonas. “Phase-Locked Inhibition, but Not Excitation, Underlies Hippocampal Ripple Oscillations in Awake Mice in Vivo.” Neuron. Elsevier, 2017. https://doi.org/10.1016/j.neuron.2016.12.018. ieee: J. Gan, S.-M. Weng, A. Pernia-Andrade, J. L. Csicsvari, and P. M. Jonas, “Phase-locked inhibition, but not excitation, underlies hippocampal ripple oscillations in awake mice in vivo,” Neuron, vol. 93, no. 2. Elsevier, pp. 308–314, 2017. ista: Gan J, Weng S-M, Pernia-Andrade A, Csicsvari JL, Jonas PM. 2017. Phase-locked inhibition, but not excitation, underlies hippocampal ripple oscillations in awake mice in vivo. Neuron. 93(2), 308–314. mla: Gan, Jian, et al. “Phase-Locked Inhibition, but Not Excitation, Underlies Hippocampal Ripple Oscillations in Awake Mice in Vivo.” Neuron, vol. 93, no. 2, Elsevier, 2017, pp. 308–14, doi:10.1016/j.neuron.2016.12.018. short: J. Gan, S.-M. Weng, A. Pernia-Andrade, J.L. Csicsvari, P.M. Jonas, Neuron 93 (2017) 308–314. date_created: 2018-12-11T11:50:15Z date_published: 2017-01-18T00:00:00Z date_updated: 2023-09-20T11:31:48Z day: '18' ddc: - '571' department: - _id: PeJo - _id: JoCs doi: 10.1016/j.neuron.2016.12.018 ec_funded: 1 external_id: isi: - '000396428200010' file: - access_level: open_access content_type: application/pdf creator: system date_created: 2018-12-12T10:08:56Z date_updated: 2018-12-12T10:08:56Z file_id: '4719' file_name: IST-2017-752-v1+1_1-s2.0-S0896627316309606-main.pdf file_size: 2738950 relation: main_file file_date_updated: 2018-12-12T10:08:56Z has_accepted_license: '1' intvolume: ' 93' isi: 1 issue: '2' language: - iso: eng month: '01' oa: 1 oa_version: Published Version page: 308 - 314 project: - _id: 25C26B1E-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: P24909-B24 name: Mechanisms of transmitter release at GABAergic synapses - _id: 25C0F108-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '268548' name: Nanophysiology of fast-spiking, parvalbumin-expressing GABAergic interneurons publication: Neuron publication_status: published publisher: Elsevier publist_id: '6244' pubrep_id: '752' quality_controlled: '1' scopus_import: '1' status: public title: Phase-locked inhibition, but not excitation, underlies hippocampal ripple oscillations in awake mice in vivo tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 93 year: '2017' ... --- _id: '1117' abstract: - lang: eng text: 'GABAergic synapses in brain circuits generate inhibitory output signals with submillisecond latency and temporal precision. Whether the molecular identity of the release sensor contributes to these signaling properties remains unclear. Here, we examined the Ca^2+ sensor of exocytosis at GABAergic basket cell (BC) to Purkinje cell (PC) synapses in cerebellum. Immunolabeling suggested that BC terminals selectively expressed synaptotagmin 2 (Syt2), whereas synaptotagmin 1 (Syt1) was enriched in excitatory terminals. Genetic elimination of Syt2 reduced action potential-evoked release to ∼10%, identifying Syt2 as the major Ca^2+ sensor at BC-PC synapses. Differential adenovirus-mediated rescue revealed that Syt2 triggered release with shorter latency and higher temporal precision and mediated faster vesicle pool replenishment than Syt1. Furthermore, deletion of Syt2 severely reduced and delayed disynaptic inhibition following parallel fiber stimulation. Thus, the selective use of Syt2 as release sensor at BC-PC synapses ensures fast and efficient feedforward inhibition in cerebellar microcircuits. #bioimagingfacility-author' acknowledged_ssus: - _id: Bio - _id: PreCl article_processing_charge: No author: - first_name: Chong full_name: Chen, Chong id: 3DFD581A-F248-11E8-B48F-1D18A9856A87 last_name: Chen - first_name: Itaru full_name: Arai, Itaru id: 32A73F6C-F248-11E8-B48F-1D18A9856A87 last_name: Arai - first_name: Rachel full_name: Satterield, Rachel last_name: Satterield - first_name: Samuel full_name: Young, Samuel last_name: Young - first_name: Peter M full_name: Jonas, Peter M id: 353C1B58-F248-11E8-B48F-1D18A9856A87 last_name: Jonas orcid: 0000-0001-5001-4804 citation: ama: Chen C, Arai itaru, Satterield R, Young S, Jonas PM. Synaptotagmin 2 is the fast Ca2+ sensor at a central inhibitory synapse. Cell Reports. 2017;18(3):723-736. doi:10.1016/j.celrep.2016.12.067 apa: Chen, C., Arai, itaru, Satterield, R., Young, S., & Jonas, P. M. (2017). Synaptotagmin 2 is the fast Ca2+ sensor at a central inhibitory synapse. Cell Reports. Cell Press. https://doi.org/10.1016/j.celrep.2016.12.067 chicago: Chen, Chong, itaru Arai, Rachel Satterield, Samuel Young, and Peter M Jonas. “Synaptotagmin 2 Is the Fast Ca2+ Sensor at a Central Inhibitory Synapse.” Cell Reports. Cell Press, 2017. https://doi.org/10.1016/j.celrep.2016.12.067. ieee: C. Chen, itaru Arai, R. Satterield, S. Young, and P. M. Jonas, “Synaptotagmin 2 is the fast Ca2+ sensor at a central inhibitory synapse,” Cell Reports, vol. 18, no. 3. Cell Press, pp. 723–736, 2017. ista: Chen C, Arai itaru, Satterield R, Young S, Jonas PM. 2017. Synaptotagmin 2 is the fast Ca2+ sensor at a central inhibitory synapse. Cell Reports. 18(3), 723–736. mla: Chen, Chong, et al. “Synaptotagmin 2 Is the Fast Ca2+ Sensor at a Central Inhibitory Synapse.” Cell Reports, vol. 18, no. 3, Cell Press, 2017, pp. 723–36, doi:10.1016/j.celrep.2016.12.067. short: C. Chen, itaru Arai, R. Satterield, S. Young, P.M. Jonas, Cell Reports 18 (2017) 723–736. date_created: 2018-12-11T11:50:14Z date_published: 2017-01-17T00:00:00Z date_updated: 2023-09-20T11:32:15Z day: '17' ddc: - '571' department: - _id: PeJo doi: 10.1016/j.celrep.2016.12.067 ec_funded: 1 external_id: isi: - '000396470600013' file: - access_level: open_access content_type: application/pdf creator: system date_created: 2018-12-12T10:16:09Z date_updated: 2018-12-12T10:16:09Z file_id: '5195' file_name: IST-2017-751-v1+1_1-s2.0-S2211124716317740-main.pdf file_size: 4427591 relation: main_file file_date_updated: 2018-12-12T10:16:09Z has_accepted_license: '1' intvolume: ' 18' isi: 1 issue: '3' language: - iso: eng month: '01' oa: 1 oa_version: Published Version page: 723 - 736 project: - _id: 25C26B1E-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: P24909-B24 name: Mechanisms of transmitter release at GABAergic synapses - _id: 25C0F108-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '268548' name: Nanophysiology of fast-spiking, parvalbumin-expressing GABAergic interneurons publication: Cell Reports publication_identifier: issn: - '22111247' publication_status: published publisher: Cell Press publist_id: '6245' pubrep_id: '751' quality_controlled: '1' related_material: record: - id: '324' relation: dissertation_contains status: public scopus_import: '1' status: public title: Synaptotagmin 2 is the fast Ca2+ sensor at a central inhibitory synapse tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 18 year: '2017' ...