[{"isi":1,"quality_controlled":"1","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"external_id":{"isi":["000535574200201"],"pmid":["32252271"]},"language":[{"iso":"eng"}],"doi":"10.3390/ijms21072459","month":"04","publication_identifier":{"eissn":["14220067"]},"publication_status":"published","publisher":"MDPI","department":[{"_id":"RySh"}],"year":"2020","pmid":1,"date_updated":"2023-08-21T06:13:19Z","date_created":"2020-04-19T22:00:55Z","volume":21,"author":[{"full_name":"Martín-Belmonte, Alejandro","first_name":"Alejandro","last_name":"Martín-Belmonte"},{"first_name":"Carolina","last_name":"Aguado","full_name":"Aguado, Carolina"},{"last_name":"Alfaro-Ruíz","first_name":"Rocío","full_name":"Alfaro-Ruíz, Rocío"},{"first_name":"Ana Esther","last_name":"Moreno-Martínez","full_name":"Moreno-Martínez, Ana Esther"},{"full_name":"De La Ossa, Luis","first_name":"Luis","last_name":"De La Ossa"},{"last_name":"Martínez-Hernández","first_name":"José","full_name":"Martínez-Hernández, José"},{"full_name":"Buisson, Alain","last_name":"Buisson","first_name":"Alain"},{"id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8761-9444","first_name":"Ryuichi","last_name":"Shigemoto","full_name":"Shigemoto, Ryuichi"},{"last_name":"Fukazawa","first_name":"Yugo","full_name":"Fukazawa, Yugo"},{"last_name":"Luján","first_name":"Rafael","full_name":"Luján, Rafael"}],"article_number":"2459","file_date_updated":"2020-07-14T12:48:01Z","article_type":"original","publication":"International journal of molecular sciences","citation":{"chicago":"Martín-Belmonte, Alejandro, Carolina Aguado, Rocío Alfaro-Ruíz, Ana Esther Moreno-Martínez, Luis De La Ossa, José Martínez-Hernández, Alain Buisson, Ryuichi Shigemoto, Yugo Fukazawa, and Rafael Luján. “Density of GABAB Receptors Is Reduced in Granule Cells of the Hippocampus in a Mouse Model of Alzheimer’s Disease.” International Journal of Molecular Sciences. MDPI, 2020. https://doi.org/10.3390/ijms21072459.","mla":"Martín-Belmonte, Alejandro, et al. “Density of GABAB Receptors Is Reduced in Granule Cells of the Hippocampus in a Mouse Model of Alzheimer’s Disease.” International Journal of Molecular Sciences, vol. 21, no. 7, 2459, MDPI, 2020, doi:10.3390/ijms21072459.","short":"A. Martín-Belmonte, C. Aguado, R. Alfaro-Ruíz, A.E. Moreno-Martínez, L. De La Ossa, J. Martínez-Hernández, A. Buisson, R. Shigemoto, Y. Fukazawa, R. Luján, International Journal of Molecular Sciences 21 (2020).","ista":"Martín-Belmonte A, Aguado C, Alfaro-Ruíz R, Moreno-Martínez AE, De La Ossa L, Martínez-Hernández J, Buisson A, Shigemoto R, Fukazawa Y, Luján R. 2020. Density of GABAB receptors is reduced in granule cells of the hippocampus in a mouse model of Alzheimer’s disease. International journal of molecular sciences. 21(7), 2459.","ieee":"A. Martín-Belmonte et al., “Density of GABAB receptors is reduced in granule cells of the hippocampus in a mouse model of Alzheimer’s disease,” International journal of molecular sciences, vol. 21, no. 7. MDPI, 2020.","apa":"Martín-Belmonte, A., Aguado, C., Alfaro-Ruíz, R., Moreno-Martínez, A. E., De La Ossa, L., Martínez-Hernández, J., … Luján, R. (2020). Density of GABAB receptors is reduced in granule cells of the hippocampus in a mouse model of Alzheimer’s disease. International Journal of Molecular Sciences. MDPI. https://doi.org/10.3390/ijms21072459","ama":"Martín-Belmonte A, Aguado C, Alfaro-Ruíz R, et al. Density of GABAB receptors is reduced in granule cells of the hippocampus in a mouse model of Alzheimer’s disease. International journal of molecular sciences. 2020;21(7). doi:10.3390/ijms21072459"},"date_published":"2020-04-02T00:00:00Z","scopus_import":"1","day":"02","article_processing_charge":"No","has_accepted_license":"1","status":"public","title":"Density of GABAB receptors is reduced in granule cells of the hippocampus in a mouse model of Alzheimer's disease","ddc":["570"],"intvolume":" 21","_id":"7664","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","file":[{"file_size":2941197,"content_type":"application/pdf","creator":"dernst","file_name":"2020_JournMolecSciences_Martin_Belmonte.pdf","access_level":"open_access","date_updated":"2020-07-14T12:48:01Z","date_created":"2020-04-20T11:43:18Z","checksum":"b9d2f1657d8c4a74b01a62b474d009b0","relation":"main_file","file_id":"7669"}],"oa_version":"Published Version","type":"journal_article","abstract":[{"text":"Metabotropic γ-aminobutyric acid (GABAB) receptors contribute to the control of network activity and information processing in hippocampal circuits by regulating neuronal excitability and synaptic transmission. The dysfunction in the dentate gyrus (DG) has been implicated in Alzheimer´s disease (AD). Given the involvement of GABAB receptors in AD, to determine their subcellular localisation and possible alteration in granule cells of the DG in a mouse model of AD at 12 months of age, we used high-resolution immunoelectron microscopic analysis. Immunohistochemistry at the light microscopic level showed that the regional and cellular expression pattern of GABAB1 was similar in an AD model mouse expressing mutated human amyloid precursor protein and presenilin1 (APP/PS1) and in age-matched wild type mice. High-resolution immunoelectron microscopy revealed a distance-dependent gradient of immunolabelling for GABAB receptors, increasing from proximal to distal dendrites in both wild type and APP/PS1 mice. However, the overall density of GABAB receptors at the neuronal surface of these postsynaptic compartments of granule cells was significantly reduced in APP/PS1 mice. Parallel to this reduction in surface receptors, we found a significant increase in GABAB1 at cytoplasmic sites. GABAB receptors were also detected at presynaptic sites in the molecular layer of the DG. We also found a decrease in plasma membrane GABAB receptors in axon terminals contacting dendritic spines of granule cells, which was more pronounced in the outer than in the inner molecular layer. Altogether, our data showing post- and presynaptic reduction in surface GABAB receptors in the DG suggest the alteration of the GABAB-mediated modulation of excitability and synaptic transmission in granule cells, which may contribute to the cognitive dysfunctions in the APP/PS1 model of AD","lang":"eng"}],"issue":"7"},{"abstract":[{"text":"Acute brain slice preparation is a powerful experimental model for investigating the characteristics of synaptic function in the brain. Although brain tissue is usually cut at ice-cold temperature (CT) to facilitate slicing and avoid neuronal damage, exposure to CT causes molecular and architectural changes of synapses. To address these issues, we investigated ultrastructural and electrophysiological features of synapses in mouse acute cerebellar slices prepared at ice-cold and physiological temperature (PT). In the slices prepared at CT, we found significant spine loss and reconstruction, synaptic vesicle rearrangement and decrease in synaptic proteins, all of which were not detected in slices prepared at PT. Consistent with these structural findings, slices prepared at PT showed higher release probability. Furthermore, preparation at PT allows electrophysiological recording immediately after slicing resulting in higher detectability of long-term depression (LTD) after motor learning compared with that at CT. These results indicate substantial advantages of the slice preparation at PT for investigating synaptic functions in different physiological conditions.","lang":"eng"}],"type":"journal_article","file":[{"creator":"dernst","content_type":"application/pdf","file_size":9227283,"file_name":"2020_FrontiersCellularNeurosc_Eguchi.pdf","access_level":"open_access","date_created":"2020-04-20T10:59:49Z","date_updated":"2020-07-14T12:48:01Z","checksum":"1c145123c6f8dc3e2e4bd5a66a1ad60e","file_id":"7668","relation":"main_file"}],"oa_version":"Published Version","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"7665","status":"public","ddc":["570"],"title":"Advantages of acute brain slices prepared at physiological temperature in the characterization of synaptic functions","intvolume":" 14","day":"19","has_accepted_license":"1","article_processing_charge":"Yes (via OA deal)","scopus_import":"1","date_published":"2020-03-19T00:00:00Z","publication":"Frontiers in Cellular Neuroscience","citation":{"short":"K. Eguchi, P. Velicky, E. Saeckl, M. Itakura, Y. Fukazawa, J.G. Danzl, R. Shigemoto, Frontiers in Cellular Neuroscience 14 (2020).","mla":"Eguchi, Kohgaku, et al. “Advantages of Acute Brain Slices Prepared at Physiological Temperature in the Characterization of Synaptic Functions.” Frontiers in Cellular Neuroscience, vol. 14, 63, Frontiers Media, 2020, doi:10.3389/fncel.2020.00063.","chicago":"Eguchi, Kohgaku, Philipp Velicky, Elena Saeckl, Makoto Itakura, Yugo Fukazawa, Johann G Danzl, and Ryuichi Shigemoto. “Advantages of Acute Brain Slices Prepared at Physiological Temperature in the Characterization of Synaptic Functions.” Frontiers in Cellular Neuroscience. Frontiers Media, 2020. https://doi.org/10.3389/fncel.2020.00063.","ama":"Eguchi K, Velicky P, Saeckl E, et al. Advantages of acute brain slices prepared at physiological temperature in the characterization of synaptic functions. Frontiers in Cellular Neuroscience. 2020;14. doi:10.3389/fncel.2020.00063","apa":"Eguchi, K., Velicky, P., Saeckl, E., Itakura, M., Fukazawa, Y., Danzl, J. G., & Shigemoto, R. (2020). Advantages of acute brain slices prepared at physiological temperature in the characterization of synaptic functions. Frontiers in Cellular Neuroscience. Frontiers Media. https://doi.org/10.3389/fncel.2020.00063","ieee":"K. Eguchi et al., “Advantages of acute brain slices prepared at physiological temperature in the characterization of synaptic functions,” Frontiers in Cellular Neuroscience, vol. 14. Frontiers Media, 2020.","ista":"Eguchi K, Velicky P, Saeckl E, Itakura M, Fukazawa Y, Danzl JG, Shigemoto R. 2020. Advantages of acute brain slices prepared at physiological temperature in the characterization of synaptic functions. Frontiers in Cellular Neuroscience. 14, 63."},"article_type":"original","file_date_updated":"2020-07-14T12:48:01Z","ec_funded":1,"article_number":"63","author":[{"full_name":"Eguchi, Kohgaku","id":"2B7846DC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6170-2546","first_name":"Kohgaku","last_name":"Eguchi"},{"first_name":"Philipp","last_name":"Velicky","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-2340-7431","full_name":"Velicky, Philipp"},{"first_name":"Elena","last_name":"Hollergschwandtner","id":"3C054040-F248-11E8-B48F-1D18A9856A87","full_name":"Hollergschwandtner, Elena"},{"last_name":"Itakura","first_name":"Makoto","full_name":"Itakura, Makoto"},{"full_name":"Fukazawa, Yugo","last_name":"Fukazawa","first_name":"Yugo"},{"full_name":"Danzl, Johann G","last_name":"Danzl","first_name":"Johann G","orcid":"0000-0001-8559-3973","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Shigemoto, Ryuichi","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8761-9444","first_name":"Ryuichi","last_name":"Shigemoto"}],"date_updated":"2023-08-21T06:12:48Z","date_created":"2020-04-19T22:00:55Z","volume":14,"year":"2020","publication_status":"published","department":[{"_id":"JoDa"},{"_id":"RySh"}],"publisher":"Frontiers Media","month":"03","publication_identifier":{"issn":["16625102"]},"doi":"10.3389/fncel.2020.00063","language":[{"iso":"eng"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"isi":["000525582200001"]},"oa":1,"isi":1,"quality_controlled":"1","project":[{"call_identifier":"H2020","name":"Ultrastructural analysis of phosphoinositides in nerve terminals: distribution, dynamics and physiological roles in synaptic transmission","grant_number":"793482","_id":"2659CC84-B435-11E9-9278-68D0E5697425"},{"grant_number":"694539","_id":"25CA28EA-B435-11E9-9278-68D0E5697425","name":"In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour","call_identifier":"H2020"},{"_id":"265CB4D0-B435-11E9-9278-68D0E5697425","grant_number":"I03600","call_identifier":"FWF","name":"Optical control of synaptic function via adhesion molecules"},{"name":"IST Austria Open Access Fund","_id":"B67AFEDC-15C9-11EA-A837-991A96BB2854"}]},{"file_date_updated":"2020-07-14T12:48:04Z","article_number":"e56839","volume":9,"date_updated":"2023-08-21T06:26:50Z","date_created":"2020-05-24T22:00:58Z","author":[{"full_name":"Bao, Jin","first_name":"Jin","last_name":"Bao"},{"last_name":"Graupner","first_name":"Michael","full_name":"Graupner, Michael"},{"full_name":"Astorga, Guadalupe","first_name":"Guadalupe","last_name":"Astorga"},{"last_name":"Collin","first_name":"Thibault","full_name":"Collin, Thibault"},{"last_name":"Jalil","first_name":"Abdelali","full_name":"Jalil, Abdelali"},{"last_name":"Indriati","first_name":"Dwi Wahyu","full_name":"Indriati, Dwi Wahyu"},{"full_name":"Bradley, Jonathan","first_name":"Jonathan","last_name":"Bradley"},{"full_name":"Shigemoto, Ryuichi","first_name":"Ryuichi","last_name":"Shigemoto","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8761-9444"},{"full_name":"Llano, Isabel","first_name":"Isabel","last_name":"Llano"}],"publisher":"eLife Sciences Publications","department":[{"_id":"RySh"}],"publication_status":"published","pmid":1,"year":"2020","publication_identifier":{"eissn":["2050084X"]},"month":"05","language":[{"iso":"eng"}],"doi":"10.7554/eLife.56839","isi":1,"quality_controlled":"1","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"external_id":{"pmid":["32401196"],"isi":["000535191600001"]},"abstract":[{"lang":"eng","text":"Type 1 metabotropic glutamate receptors (mGluR1s) are key elements in neuronal signaling. While their function is well documented in slices, requirements for their activation in vivo are poorly understood. We examine this question in adult mice in vivo using 2-photon imaging of cerebellar molecular layer interneurons (MLIs) expressing GCaMP. In anesthetized mice, parallel fiber activation evokes beam-like Cai rises in postsynaptic MLIs which depend on co-activation of mGluR1s and ionotropic glutamate receptors (iGluRs). In awake mice, blocking mGluR1 decreases Cai rises associated with locomotion. In vitro studies and freeze-fracture electron microscopy show that the iGluR-mGluR1 interaction is synergistic and favored by close association of the two classes of receptors. Altogether our results suggest that mGluR1s, acting in synergy with iGluRs, potently contribute to processing cerebellar neuronal signaling under physiological conditions."}],"type":"journal_article","file":[{"date_created":"2020-05-26T09:34:54Z","date_updated":"2020-07-14T12:48:04Z","checksum":"8ea99bb6660cc407dbdb00c173b01683","relation":"main_file","file_id":"7891","content_type":"application/pdf","file_size":4832050,"creator":"dernst","file_name":"2020_eLife_Bao.pdf","access_level":"open_access"}],"oa_version":"Published Version","intvolume":" 9","ddc":["570"],"title":"Synergism of type 1 metabotropic and ionotropic glutamate receptors in cerebellar molecular layer interneurons in vivo","status":"public","_id":"7878","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","has_accepted_license":"1","article_processing_charge":"No","day":"13","scopus_import":"1","date_published":"2020-05-13T00:00:00Z","article_type":"original","citation":{"ama":"Bao J, Graupner M, Astorga G, et al. Synergism of type 1 metabotropic and ionotropic glutamate receptors in cerebellar molecular layer interneurons in vivo. eLife. 2020;9. doi:10.7554/eLife.56839","apa":"Bao, J., Graupner, M., Astorga, G., Collin, T., Jalil, A., Indriati, D. W., … Llano, I. (2020). Synergism of type 1 metabotropic and ionotropic glutamate receptors in cerebellar molecular layer interneurons in vivo. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.56839","ieee":"J. Bao et al., “Synergism of type 1 metabotropic and ionotropic glutamate receptors in cerebellar molecular layer interneurons in vivo,” eLife, vol. 9. eLife Sciences Publications, 2020.","ista":"Bao J, Graupner M, Astorga G, Collin T, Jalil A, Indriati DW, Bradley J, Shigemoto R, Llano I. 2020. Synergism of type 1 metabotropic and ionotropic glutamate receptors in cerebellar molecular layer interneurons in vivo. eLife. 9, e56839.","short":"J. Bao, M. Graupner, G. Astorga, T. Collin, A. Jalil, D.W. Indriati, J. Bradley, R. Shigemoto, I. Llano, ELife 9 (2020).","mla":"Bao, Jin, et al. “Synergism of Type 1 Metabotropic and Ionotropic Glutamate Receptors in Cerebellar Molecular Layer Interneurons in Vivo.” ELife, vol. 9, e56839, eLife Sciences Publications, 2020, doi:10.7554/eLife.56839.","chicago":"Bao, Jin, Michael Graupner, Guadalupe Astorga, Thibault Collin, Abdelali Jalil, Dwi Wahyu Indriati, Jonathan Bradley, Ryuichi Shigemoto, and Isabel Llano. “Synergism of Type 1 Metabotropic and Ionotropic Glutamate Receptors in Cerebellar Molecular Layer Interneurons in Vivo.” ELife. eLife Sciences Publications, 2020. https://doi.org/10.7554/eLife.56839."},"publication":"eLife"},{"article_type":"original","page":"4103-4115","publication":"Journal of Neuroscience","citation":{"chicago":"Wang, Han Ying, Kohgaku Eguchi, Takayuki Yamashita, and Tomoyuki Takahashi. “Frequency-Dependent Block of Excitatory Neurotransmission by Isoflurane via Dual Presynaptic Mechanisms.” Journal of Neuroscience. Society for Neuroscience, 2020. https://doi.org/10.1523/JNEUROSCI.2946-19.2020.","short":"H.Y. Wang, K. Eguchi, T. Yamashita, T. Takahashi, Journal of Neuroscience 40 (2020) 4103–4115.","mla":"Wang, Han Ying, et al. “Frequency-Dependent Block of Excitatory Neurotransmission by Isoflurane via Dual Presynaptic Mechanisms.” Journal of Neuroscience, vol. 40, no. 21, Society for Neuroscience, 2020, pp. 4103–15, doi:10.1523/JNEUROSCI.2946-19.2020.","apa":"Wang, H. Y., Eguchi, K., Yamashita, T., & Takahashi, T. (2020). Frequency-dependent block of excitatory neurotransmission by isoflurane via dual presynaptic mechanisms. Journal of Neuroscience. Society for Neuroscience. https://doi.org/10.1523/JNEUROSCI.2946-19.2020","ieee":"H. Y. Wang, K. Eguchi, T. Yamashita, and T. Takahashi, “Frequency-dependent block of excitatory neurotransmission by isoflurane via dual presynaptic mechanisms,” Journal of Neuroscience, vol. 40, no. 21. Society for Neuroscience, pp. 4103–4115, 2020.","ista":"Wang HY, Eguchi K, Yamashita T, Takahashi T. 2020. Frequency-dependent block of excitatory neurotransmission by isoflurane via dual presynaptic mechanisms. Journal of Neuroscience. 40(21), 4103–4115.","ama":"Wang HY, Eguchi K, Yamashita T, Takahashi T. Frequency-dependent block of excitatory neurotransmission by isoflurane via dual presynaptic mechanisms. Journal of Neuroscience. 2020;40(21):4103-4115. doi:10.1523/JNEUROSCI.2946-19.2020"},"date_published":"2020-05-20T00:00:00Z","scopus_import":"1","day":"20","article_processing_charge":"No","has_accepted_license":"1","ddc":["570"],"status":"public","title":"Frequency-dependent block of excitatory neurotransmission by isoflurane via dual presynaptic mechanisms","intvolume":" 40","_id":"7908","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","file":[{"creator":"dernst","file_size":3817360,"content_type":"application/pdf","file_name":"2020_JourNeuroscience_Wang.pdf","access_level":"open_access","date_updated":"2020-07-14T12:48:05Z","date_created":"2020-06-02T09:12:16Z","checksum":"6571607ea9036154b67cc78e848a7f7d","file_id":"7912","relation":"main_file"}],"oa_version":"Published Version","type":"journal_article","abstract":[{"lang":"eng","text":"Volatile anesthetics are widely used for surgery, but neuronal mechanisms of anesthesia remain unidentified. At the calyx of Held in brainstem slices from rats of either sex, isoflurane at clinical doses attenuated EPSCs by decreasing the release probability and the number of readily releasable vesicles. In presynaptic recordings of Ca2+ currents and exocytic capacitance changes, isoflurane attenuated exocytosis by inhibiting Ca2+ currents evoked by a short presynaptic depolarization, whereas it inhibited exocytosis evoked by a prolonged depolarization via directly blocking exocytic machinery downstream of Ca2+ influx. Since the length of presynaptic depolarization can simulate the frequency of synaptic inputs, isoflurane anesthesia is likely mediated by distinct dual mechanisms, depending on input frequencies. In simultaneous presynaptic and postsynaptic action potential recordings, isoflurane impaired the fidelity of repetitive spike transmission, more strongly at higher frequencies. Furthermore, in the cerebrum of adult mice, isoflurane inhibited monosynaptic corticocortical spike transmission, preferentially at a higher frequency. We conclude that dual presynaptic mechanisms operate for the anesthetic action of isoflurane, of which direct inhibition of exocytic machinery plays a low-pass filtering role in spike transmission at central excitatory synapses."}],"issue":"21","quality_controlled":"1","isi":1,"external_id":{"isi":["000535694700004"]},"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"language":[{"iso":"eng"}],"doi":"10.1523/JNEUROSCI.2946-19.2020","month":"05","publication_identifier":{"eissn":["15292401"]},"publication_status":"published","publisher":"Society for Neuroscience","department":[{"_id":"RySh"}],"year":"2020","date_updated":"2023-08-21T06:31:25Z","date_created":"2020-05-31T22:00:48Z","volume":40,"author":[{"full_name":"Wang, Han Ying","last_name":"Wang","first_name":"Han Ying"},{"orcid":"0000-0002-6170-2546","id":"2B7846DC-F248-11E8-B48F-1D18A9856A87","last_name":"Eguchi","first_name":"Kohgaku","full_name":"Eguchi, Kohgaku"},{"full_name":"Yamashita, Takayuki","first_name":"Takayuki","last_name":"Yamashita"},{"full_name":"Takahashi, Tomoyuki","first_name":"Tomoyuki","last_name":"Takahashi"}],"file_date_updated":"2020-07-14T12:48:05Z"},{"author":[{"full_name":"Martín-Belmonte, Alejandro","first_name":"Alejandro","last_name":"Martín-Belmonte"},{"full_name":"Aguado, Carolina","last_name":"Aguado","first_name":"Carolina"},{"full_name":"Alfaro-Ruíz, Rocío","last_name":"Alfaro-Ruíz","first_name":"Rocío"},{"last_name":"Moreno-Martínez","first_name":"Ana Esther","full_name":"Moreno-Martínez, Ana Esther"},{"full_name":"De La Ossa, Luis","last_name":"De La Ossa","first_name":"Luis"},{"last_name":"Martínez-Hernández","first_name":"José","full_name":"Martínez-Hernández, José"},{"last_name":"Buisson","first_name":"Alain","full_name":"Buisson, Alain"},{"last_name":"Früh","first_name":"Simon","full_name":"Früh, Simon"},{"last_name":"Bettler","first_name":"Bernhard","full_name":"Bettler, Bernhard"},{"full_name":"Shigemoto, Ryuichi","first_name":"Ryuichi","last_name":"Shigemoto","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8761-9444"},{"last_name":"Fukazawa","first_name":"Yugo","full_name":"Fukazawa, Yugo"},{"last_name":"Luján","first_name":"Rafael","full_name":"Luján, Rafael"}],"volume":30,"date_created":"2019-12-22T23:00:43Z","date_updated":"2023-09-06T14:48:01Z","pmid":1,"year":"2020","publisher":"Wiley","department":[{"_id":"RySh"}],"publication_status":"published","ec_funded":1,"file_date_updated":"2020-09-22T09:47:19Z","doi":"10.1111/bpa.12802","language":[{"iso":"eng"}],"oa":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"pmid":["31729777"],"isi":["000502270900001"]},"project":[{"grant_number":"720270","_id":"25CBA828-B435-11E9-9278-68D0E5697425","name":"Human Brain Project Specific Grant Agreement 1 (HBP SGA 1)","call_identifier":"H2020"},{"name":"Human Brain Project Specific Grant Agreement 2 (HBP SGA 2)","call_identifier":"H2020","grant_number":"785907","_id":"26436750-B435-11E9-9278-68D0E5697425"}],"quality_controlled":"1","isi":1,"publication_identifier":{"issn":["10156305"],"eissn":["17503639"]},"month":"05","oa_version":"Published Version","file":[{"checksum":"549cc1b18f638a21d17a939ba5563fa9","success":1,"date_created":"2020-09-22T09:47:19Z","date_updated":"2020-09-22T09:47:19Z","relation":"main_file","file_id":"8554","content_type":"application/pdf","file_size":4220935,"creator":"dernst","access_level":"open_access","file_name":"2020_BrainPathology_MartinBelmonte.pdf"}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","_id":"7207","intvolume":" 30","status":"public","ddc":["570"],"title":"Reduction in the neuronal surface of post and presynaptic GABA>B< receptors in the hippocampus in a mouse model of Alzheimer's disease","issue":"3","abstract":[{"text":"The hippocampus plays key roles in learning and memory and is a main target of Alzheimer's disease (AD), which causes progressive memory impairments. Despite numerous investigations about the processes required for the normal hippocampal functions, the neurotransmitter receptors involved in the synaptic deficits by which AD disables the hippocampus are not yet characterized. By combining histoblots, western blots, immunohistochemistry and high‐resolution immunoelectron microscopic methods for GABAB receptors, this study provides a quantitative description of the expression and the subcellular localization of GABAB1 in the hippocampus in a mouse model of AD at 1, 6 and 12 months of age. Western blots and histoblots showed that the total amount of protein and the laminar expression pattern of GABAB1 were similar in APP/PS1 mice and in age‐matched wild‐type mice. In contrast, immunoelectron microscopic techniques showed that the subcellular localization of GABAB1 subunit did not change significantly in APP/PS1 mice at 1 month of age, was significantly reduced in the stratum lacunosum‐moleculare of CA1 pyramidal cells at 6 months of age and significantly reduced at the membrane surface of CA1 pyramidal cells at 12 months of age. This reduction of plasma membrane GABAB1 was paralleled by a significant increase of the subunit at the intracellular sites. We further observed a decrease of membrane‐targeted GABAB receptors in axon terminals contacting CA1 pyramidal cells. Our data demonstrate compartment‐ and age‐dependent reduction of plasma membrane‐targeted GABAB receptors in the CA1 region of the hippocampus, suggesting that this decrease might be enough to alter the GABAB‐mediated synaptic transmission taking place in AD.","lang":"eng"}],"type":"journal_article","date_published":"2020-05-01T00:00:00Z","citation":{"chicago":"Martín-Belmonte, Alejandro, Carolina Aguado, Rocío Alfaro-Ruíz, Ana Esther Moreno-Martínez, Luis De La Ossa, José Martínez-Hernández, Alain Buisson, et al. “Reduction in the Neuronal Surface of Post and Presynaptic GABA>B< Receptors in the Hippocampus in a Mouse Model of Alzheimer’s Disease.” Brain Pathology. Wiley, 2020. https://doi.org/10.1111/bpa.12802.","mla":"Martín-Belmonte, Alejandro, et al. “Reduction in the Neuronal Surface of Post and Presynaptic GABA>B< Receptors in the Hippocampus in a Mouse Model of Alzheimer’s Disease.” Brain Pathology, vol. 30, no. 3, Wiley, 2020, pp. 554–75, doi:10.1111/bpa.12802.","short":"A. Martín-Belmonte, C. Aguado, R. Alfaro-Ruíz, A.E. Moreno-Martínez, L. De La Ossa, J. Martínez-Hernández, A. Buisson, S. Früh, B. Bettler, R. Shigemoto, Y. Fukazawa, R. Luján, Brain Pathology 30 (2020) 554–575.","ista":"Martín-Belmonte A, Aguado C, Alfaro-Ruíz R, Moreno-Martínez AE, De La Ossa L, Martínez-Hernández J, Buisson A, Früh S, Bettler B, Shigemoto R, Fukazawa Y, Luján R. 2020. Reduction in the neuronal surface of post and presynaptic GABA>B< receptors in the hippocampus in a mouse model of Alzheimer’s disease. Brain Pathology. 30(3), 554–575.","apa":"Martín-Belmonte, A., Aguado, C., Alfaro-Ruíz, R., Moreno-Martínez, A. E., De La Ossa, L., Martínez-Hernández, J., … Luján, R. (2020). Reduction in the neuronal surface of post and presynaptic GABA>B< receptors in the hippocampus in a mouse model of Alzheimer’s disease. Brain Pathology. Wiley. https://doi.org/10.1111/bpa.12802","ieee":"A. Martín-Belmonte et al., “Reduction in the neuronal surface of post and presynaptic GABA>B< receptors in the hippocampus in a mouse model of Alzheimer’s disease,” Brain Pathology, vol. 30, no. 3. Wiley, pp. 554–575, 2020.","ama":"Martín-Belmonte A, Aguado C, Alfaro-Ruíz R, et al. Reduction in the neuronal surface of post and presynaptic GABA>B< receptors in the hippocampus in a mouse model of Alzheimer’s disease. Brain Pathology. 2020;30(3):554-575. doi:10.1111/bpa.12802"},"publication":"Brain Pathology","page":"554-575","article_type":"original","has_accepted_license":"1","article_processing_charge":"No","day":"01","scopus_import":"1"},{"year":"2020","publication_status":"published","publisher":"Institute of Science and Technology Austria","department":[{"_id":"RySh"}],"author":[{"full_name":"Bhandari, Pradeep","orcid":"0000-0003-0863-4481","id":"45EDD1BC-F248-11E8-B48F-1D18A9856A87","last_name":"Bhandari","first_name":"Pradeep"}],"date_updated":"2023-09-07T13:20:03Z","date_created":"2020-02-26T10:56:37Z","file_date_updated":"2021-03-01T23:30:04Z","oa":1,"doi":"10.15479/AT:ISTA:7525","supervisor":[{"id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8761-9444","first_name":"Ryuichi","last_name":"Shigemoto","full_name":"Shigemoto, Ryuichi"}],"acknowledged_ssus":[{"_id":"EM-Fac"}],"degree_awarded":"PhD","language":[{"iso":"eng"}],"month":"02","publication_identifier":{"issn":["2663-337X"]},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","_id":"7525","status":"public","ddc":["570"],"title":"Localization and functional role of Cav2.3 in the medial habenula to interpeduncular nucleus pathway","oa_version":"Published Version","file":[{"file_id":"7538","embargo":"2021-02-28","title":"Localization and functional role of Cav2.3 in the medial habenula to interpeduncular nucleus pathway","relation":"main_file","date_created":"2020-02-28T08:37:53Z","date_updated":"2021-03-01T23:30:04Z","checksum":"4589234fdb12b4ad72273b311723a7b4","file_name":"Pradeep Bhandari Thesis.pdf","access_level":"open_access","creator":"pbhandari","file_size":9646346,"content_type":"application/pdf"},{"checksum":"aa79490553ca0a5c9b6fbcd152e93928","date_updated":"2021-03-01T23:30:04Z","date_created":"2020-02-28T08:47:14Z","relation":"source_file","title":"Localization and functional role of Cav2.3 in the medial habenula to interpeduncular nucleus pathway","file_id":"7539","file_size":35252164,"content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","creator":"pbhandari","access_level":"closed","embargo_to":"open_access","file_name":"Pradeep Bhandari Thesis.docx"}],"type":"dissertation","alternative_title":["ISTA Thesis"],"abstract":[{"text":"The medial habenula (MHb) is an evolutionary conserved epithalamic structure important for the modulation of emotional memory. It is involved in regulation of anxiety, compulsive behavior, addiction (nicotinic and opioid), sexual and feeding behavior. MHb receives inputs from septal regions and projects exclusively to the interpeduncular nucleus (IPN). Distinct sub-regions of the septum project to different subnuclei of MHb: the bed nucleus of anterior commissure projects to dorsal MHb and the triangular septum projects to ventral MHb. Furthermore, the dorsal and ventral MHb project to the lateral and rostral/central IPN, respectively. Importantly, these projections have unique features of prominent co-release of different neurotransmitters and requirement of a peculiar type of calcium channel for release. In general, synaptic neurotransmission requires an activity-dependent influx of Ca2+ into the presynaptic terminal through voltage-gated calcium channels. The calcium channel family most commonly involved in neurotransmitter release comprises three members, P/Q-, N- and R-type with Cav2.1, Cav2.2 and Cav2.3 subunits, respectively. In contrast to most CNS synapses that mainly express Cav2.1 and/or Cav2.2, MHb terminals in the IPN exclusively express Cav2.3. In other parts of the brain, such as the hippocampus, Cav2.3 is mostly located to postsynaptic elements. This unusual presynaptic location of Cav2.3 in the MHb-IPN pathway implies unique mechanisms of glutamate release in this pathway. One potential example of such uniqueness is the facilitation of release by GABAB receptor (GBR) activation. Presynaptic GBRs usually inhibit the release of neurotransmitters by inhibiting presynaptic calcium channels. MHb shows the highest expression levels of GBR in the brain. GBRs comprise two subunits, GABAB1 (GB1) and GABAB2 (GB2), and are associated with auxiliary subunits, called potassium channel tetramerization domain containing proteins (KCTD) 8, 12, 12b and 16. Among these four subunits, KCTD12b is exclusively expressed in ventral MHb, and KCTD8 shows the strongest expression in the whole MHb among other brain regions, indicating that KCTD8 and KCTD12b may be involved in the unique mechanisms of neurotransmitter release mediated by Cav2.3 and regulated by GBRs in this pathway. \r\nIn the present study, we first verified that neurotransmission in both dorsal and ventral MHb-IPN pathways is mainly mediated by Cav2.3 using a selective blocker of R-type channels, SNX-482. We next found that baclofen, a GBR agonist, has facilitatory effects on release from ventral MHb terminal in rostral IPN, whereas it has inhibitory effects on release from dorsal MHb terminals in lateral IPN, indicating that KCTD12b expressed exclusively in ventral MHb may have a role in the facilitatory effects of GBR activation. In a heterologous expression system using HEK cells, we found that KCTD8 and KCTD12b but not KCTD12 directly bind with Cav2.3. Pre-embedding immunogold electron microscopy data show that Cav2.3 and KCTD12b are distributed most densely in presynaptic active zone in IPN with KCTD12b being present only in rostral/central but not lateral IPN, whereas GABAB, KCTD8 and KCTD12 are distributed most densely in perisynaptic sites with KCTD12 present more frequently in postsynaptic elements and only in rostral/central IPN. In freeze-fracture replica labelling, Cav2.3, KCTD8 and KCTD12b are co-localized with each other in the same active zone indicating that they may form complexes regulating vesicle release in rostral IPN. \r\nOn electrophysiological studies of wild type (WT) mice, we found that paired-pulse ratio in rostral IPN of KCTD12b knock-out (KO) mice is lower than those of WT and KCTD8 KO mice. Consistent with this finding, in mean variance analysis, release probability in rostral IPN of KCTD12b KO mice is higher than that of WT and KCTD8 KO mice. Although paired-pulse ratios are not different between WT and KCTD8 KO mice, the mean variance analysis revealed significantly lower release probability in rostral IPN of KCTD8 KO than WT mice. These results demonstrate bidirectional regulation of Cav2.3-mediated release by KCTD8 and KCTD12b without GBR activation in rostral IPN. Finally, we examined the baclofen effects in rostral IPN of KCTD8 and KCTD12b KO mice, and found the facilitation of release remained in both KO mice, indicating that the peculiar effects of the GBR activation in this pathway do not depend on the selective expression of these KCTD subunits in ventral MHb. However, we found that presynaptic potentiation of evoked EPSC amplitude by baclofen falls to baseline after washout faster in KCTD12b KO mice than WT, KCTD8 KO and KCTD8/12b double KO mice. This result indicates that KCTD12b is involved in sustained potentiation of vesicle release by GBR activation, whereas KCTD8 is involved in its termination in the absence of KCTD12b. Consistent with these functional findings, replica labelling revealed an increase in density of KCTD8, but not Cav2.3 or GBR at active zone in rostral IPN of KCTD12b KO mice compared with that of WT mice, suggesting that increased association of KCTD8 with Cav2.3 facilitates the release probability and termination of the GBR effect in the absence of KCTD12b.\r\nIn summary, our study provided new insights into the physiological roles of presynaptic Cav2.3, GBRs and their auxiliary subunits KCTDs at an evolutionary conserved neuronal circuit. Future studies will be required to identify the exact molecular mechanism underlying the GBR-mediated presynaptic potentiation on ventral MHb terminals. It remains to be determined whether the prominent presence of presynaptic KCTDs at active zone could exert similar neuromodulatory functions in different pathways of the brain.\r\n","lang":"eng"}],"citation":{"ieee":"P. Bhandari, “Localization and functional role of Cav2.3 in the medial habenula to interpeduncular nucleus pathway,” Institute of Science and Technology Austria, 2020.","apa":"Bhandari, P. (2020). Localization and functional role of Cav2.3 in the medial habenula to interpeduncular nucleus pathway. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:7525","ista":"Bhandari P. 2020. Localization and functional role of Cav2.3 in the medial habenula to interpeduncular nucleus pathway. Institute of Science and Technology Austria.","ama":"Bhandari P. Localization and functional role of Cav2.3 in the medial habenula to interpeduncular nucleus pathway. 2020. doi:10.15479/AT:ISTA:7525","chicago":"Bhandari, Pradeep. “Localization and Functional Role of Cav2.3 in the Medial Habenula to Interpeduncular Nucleus Pathway.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:7525.","short":"P. Bhandari, Localization and Functional Role of Cav2.3 in the Medial Habenula to Interpeduncular Nucleus Pathway, Institute of Science and Technology Austria, 2020.","mla":"Bhandari, Pradeep. Localization and Functional Role of Cav2.3 in the Medial Habenula to Interpeduncular Nucleus Pathway. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:7525."},"page":"79","date_published":"2020-02-28T00:00:00Z","keyword":["Cav2.3","medial habenula (MHb)","interpeduncular nucleus (IPN)"],"day":"28","article_processing_charge":"No","has_accepted_license":"1"},{"file":[{"content_type":"application/pdf","file_size":5748456,"creator":"dernst","file_name":"2020_JournMolecSciences_Kleindienst.pdf","access_level":"open_access","date_created":"2020-09-21T14:08:58Z","date_updated":"2020-09-21T14:08:58Z","checksum":"2e4f62f3cfe945b7391fc3070e5a289f","success":1,"relation":"main_file","file_id":"8551"}],"oa_version":"Published Version","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"8532","intvolume":" 21","title":"Deep learning-assisted high-throughput analysis of freeze-fracture replica images applied to glutamate receptors and calcium channels at hippocampal synapses","ddc":["570"],"status":"public","issue":"18","abstract":[{"text":"The molecular anatomy of synapses defines their characteristics in transmission and plasticity. Precise measurements of the number and distribution of synaptic proteins are important for our understanding of synapse heterogeneity within and between brain regions. Freeze–fracture replica immunogold electron microscopy enables us to analyze them quantitatively on a two-dimensional membrane surface. Here, we introduce Darea software, which utilizes deep learning for analysis of replica images and demonstrate its usefulness for quick measurements of the pre- and postsynaptic areas, density and distribution of gold particles at synapses in a reproducible manner. We used Darea for comparing glutamate receptor and calcium channel distributions between hippocampal CA3-CA1 spine synapses on apical and basal dendrites, which differ in signaling pathways involved in synaptic plasticity. We found that apical synapses express a higher density of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and a stronger increase of AMPA receptors with synaptic size, while basal synapses show a larger increase in N-methyl-D-aspartate (NMDA) receptors with size. Interestingly, AMPA and NMDA receptors are segregated within postsynaptic sites and negatively correlated in density among both apical and basal synapses. In the presynaptic sites, Cav2.1 voltage-gated calcium channels show similar densities in apical and basal synapses with distributions consistent with an exclusion zone model of calcium channel-release site topography.","lang":"eng"}],"type":"journal_article","date_published":"2020-09-14T00:00:00Z","citation":{"mla":"Kleindienst, David, et al. “Deep Learning-Assisted High-Throughput Analysis of Freeze-Fracture Replica Images Applied to Glutamate Receptors and Calcium Channels at Hippocampal Synapses.” International Journal of Molecular Sciences, vol. 21, no. 18, 6737, MDPI, 2020, doi:10.3390/ijms21186737.","short":"D. Kleindienst, J.-C. Montanaro-Punzengruber, P. Bhandari, M.J. Case, Y. Fukazawa, R. Shigemoto, International Journal of Molecular Sciences 21 (2020).","chicago":"Kleindienst, David, Jacqueline-Claire Montanaro-Punzengruber, Pradeep Bhandari, Matthew J Case, Yugo Fukazawa, and Ryuichi Shigemoto. “Deep Learning-Assisted High-Throughput Analysis of Freeze-Fracture Replica Images Applied to Glutamate Receptors and Calcium Channels at Hippocampal Synapses.” International Journal of Molecular Sciences. MDPI, 2020. https://doi.org/10.3390/ijms21186737.","ama":"Kleindienst D, Montanaro-Punzengruber J-C, Bhandari P, Case MJ, Fukazawa Y, Shigemoto R. Deep learning-assisted high-throughput analysis of freeze-fracture replica images applied to glutamate receptors and calcium channels at hippocampal synapses. International Journal of Molecular Sciences. 2020;21(18). doi:10.3390/ijms21186737","ista":"Kleindienst D, Montanaro-Punzengruber J-C, Bhandari P, Case MJ, Fukazawa Y, Shigemoto R. 2020. Deep learning-assisted high-throughput analysis of freeze-fracture replica images applied to glutamate receptors and calcium channels at hippocampal synapses. International Journal of Molecular Sciences. 21(18), 6737.","ieee":"D. Kleindienst, J.-C. Montanaro-Punzengruber, P. Bhandari, M. J. Case, Y. Fukazawa, and R. Shigemoto, “Deep learning-assisted high-throughput analysis of freeze-fracture replica images applied to glutamate receptors and calcium channels at hippocampal synapses,” International Journal of Molecular Sciences, vol. 21, no. 18. MDPI, 2020.","apa":"Kleindienst, D., Montanaro-Punzengruber, J.-C., Bhandari, P., Case, M. J., Fukazawa, Y., & Shigemoto, R. (2020). Deep learning-assisted high-throughput analysis of freeze-fracture replica images applied to glutamate receptors and calcium channels at hippocampal synapses. International Journal of Molecular Sciences. MDPI. https://doi.org/10.3390/ijms21186737"},"publication":"International Journal of Molecular Sciences","article_type":"original","has_accepted_license":"1","article_processing_charge":"No","day":"14","scopus_import":"1","related_material":{"record":[{"id":"9562","relation":"dissertation_contains","status":"public"}]},"author":[{"full_name":"Kleindienst, David","id":"42E121A4-F248-11E8-B48F-1D18A9856A87","last_name":"Kleindienst","first_name":"David"},{"id":"3786AB44-F248-11E8-B48F-1D18A9856A87","first_name":"Jacqueline-Claire","last_name":"Montanaro-Punzengruber","full_name":"Montanaro-Punzengruber, Jacqueline-Claire"},{"orcid":"0000-0003-0863-4481","id":"45EDD1BC-F248-11E8-B48F-1D18A9856A87","last_name":"Bhandari","first_name":"Pradeep","full_name":"Bhandari, Pradeep"},{"id":"44B7CA5A-F248-11E8-B48F-1D18A9856A87","first_name":"Matthew J","last_name":"Case","full_name":"Case, Matthew J"},{"full_name":"Fukazawa, Yugo","last_name":"Fukazawa","first_name":"Yugo"},{"orcid":"0000-0001-8761-9444","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","last_name":"Shigemoto","first_name":"Ryuichi","full_name":"Shigemoto, Ryuichi"}],"volume":21,"date_updated":"2024-03-28T23:30:31Z","date_created":"2020-09-20T22:01:35Z","acknowledgement":"This research was funded by Austrian Academy of Sciences, DOC fellowship to D.K., European Research\r\nCouncil Advanced Grant 694539 and European Union Human Brain Project (HBP) SGA2 785907 to R.S.\r\nWe acknowledge Elena Hollergschwandtner for technical support.","year":"2020","publisher":"MDPI","department":[{"_id":"RySh"}],"publication_status":"published","ec_funded":1,"file_date_updated":"2020-09-21T14:08:58Z","article_number":"6737","doi":"10.3390/ijms21186737","language":[{"iso":"eng"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"isi":["000579945300001"]},"oa":1,"project":[{"grant_number":"694539","_id":"25CA28EA-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour"},{"name":"Mechanism of formation and maintenance of input side-dependent asymmetry in the hippocampus","_id":"25D32BC0-B435-11E9-9278-68D0E5697425"},{"grant_number":"785907","_id":"26436750-B435-11E9-9278-68D0E5697425","name":"Human Brain Project Specific Grant Agreement 2 (HBP SGA 2)","call_identifier":"H2020"}],"isi":1,"quality_controlled":"1","publication_identifier":{"eissn":["14220067"],"issn":["16616596"]},"month":"09"},{"file_date_updated":"2020-10-02T08:49:58Z","ec_funded":1,"year":"2019","acknowledgement":"his work was supported by the Grant-in-Aid for Scientific Research B (JSPS KAKENHI grant no. JP17H03090 to A. O.); the Scientific Research on Innovative Areas “Chemistry for Multimolecular Crowding Biosystems” (JSPS KAKENHI grant no. JP17H06349 to A. O.); and the European Union (European Research Council Advanced grant no. 694539 and Human Brain Project Ref. 720270 to R. S.). A. O. acknowledges the financial support of the Takeda Science Foundation.","publication_status":"published","department":[{"_id":"RySh"}],"publisher":"Bulletin of the Chemical Society of Japan","author":[{"full_name":"Zenmyo, Naoki","last_name":"Zenmyo","first_name":"Naoki"},{"first_name":"Hiroki","last_name":"Tokumaru","full_name":"Tokumaru, Hiroki"},{"first_name":"Shohei","last_name":"Uchinomiya","full_name":"Uchinomiya, Shohei"},{"last_name":"Fuchida","first_name":"Hirokazu","full_name":"Fuchida, Hirokazu"},{"id":"4427179E-F248-11E8-B48F-1D18A9856A87","last_name":"Tabata","first_name":"Shigekazu","full_name":"Tabata, Shigekazu"},{"full_name":"Hamachi, Itaru","first_name":"Itaru","last_name":"Hamachi"},{"full_name":"Shigemoto, Ryuichi","first_name":"Ryuichi","last_name":"Shigemoto","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8761-9444"},{"full_name":"Ojida, Akio","first_name":"Akio","last_name":"Ojida"}],"date_updated":"2021-01-12T08:08:26Z","date_created":"2019-07-21T21:59:16Z","volume":92,"month":"05","publication_identifier":{"issn":["00092673"]},"oa":1,"quality_controlled":"1","project":[{"call_identifier":"H2020","name":"In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour","_id":"25CA28EA-B435-11E9-9278-68D0E5697425","grant_number":"694539"}],"doi":"10.1246/bcsj.20190034","language":[{"iso":"eng"}],"type":"journal_article","abstract":[{"lang":"eng","text":"Chemical labeling of proteins with synthetic molecular probes offers the possibility to probe the functions of proteins of interest in living cells. However, the methods for covalently labeling targeted proteins using complementary peptide tag-probe pairs are still limited, irrespective of the versatility of such pairs in biological research. Herein, we report the new CysHis tag-Ni(II) probe pair for the specific covalent labeling of proteins. A broad-range evaluation of the reactivity profiles of the probe and the CysHis peptide tag afforded a tag-probe pair with an optimized and high labeling selectivity and reactivity. In particular, the labeling specificity of this pair was notably improved compared to the previously reported one. This pair was successfully utilized for the fluorescence imaging of membrane proteins on the surfaces of living cells, demonstrating its potential utility in biological research."}],"issue":"5","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"6659","status":"public","ddc":["570"],"title":"Optimized reaction pair of the CysHis tag and Ni(II)-NTA probe for highly selective chemical labeling of membrane proteins","intvolume":" 92","oa_version":"Published Version","file":[{"file_name":"2019_BCSJ_Zenmyo.pdf","access_level":"open_access","creator":"dernst","content_type":"application/pdf","file_size":2464903,"file_id":"8594","relation":"main_file","date_created":"2020-10-02T08:49:58Z","date_updated":"2020-10-02T08:49:58Z","success":1,"checksum":"186de511d6e0ca93f5d981e2443eb8cd"}],"scopus_import":"1","day":"15","has_accepted_license":"1","article_processing_charge":"No","publication":"Bulletin of the Chemical Society of Japan","citation":{"ista":"Zenmyo N, Tokumaru H, Uchinomiya S, Fuchida H, Tabata S, Hamachi I, Shigemoto R, Ojida A. 2019. Optimized reaction pair of the CysHis tag and Ni(II)-NTA probe for highly selective chemical labeling of membrane proteins. Bulletin of the Chemical Society of Japan. 92(5), 995–1000.","apa":"Zenmyo, N., Tokumaru, H., Uchinomiya, S., Fuchida, H., Tabata, S., Hamachi, I., … Ojida, A. (2019). Optimized reaction pair of the CysHis tag and Ni(II)-NTA probe for highly selective chemical labeling of membrane proteins. Bulletin of the Chemical Society of Japan. Bulletin of the Chemical Society of Japan. https://doi.org/10.1246/bcsj.20190034","ieee":"N. Zenmyo et al., “Optimized reaction pair of the CysHis tag and Ni(II)-NTA probe for highly selective chemical labeling of membrane proteins,” Bulletin of the Chemical Society of Japan, vol. 92, no. 5. Bulletin of the Chemical Society of Japan, pp. 995–1000, 2019.","ama":"Zenmyo N, Tokumaru H, Uchinomiya S, et al. Optimized reaction pair of the CysHis tag and Ni(II)-NTA probe for highly selective chemical labeling of membrane proteins. Bulletin of the Chemical Society of Japan. 2019;92(5):995-1000. doi:10.1246/bcsj.20190034","chicago":"Zenmyo, Naoki, Hiroki Tokumaru, Shohei Uchinomiya, Hirokazu Fuchida, Shigekazu Tabata, Itaru Hamachi, Ryuichi Shigemoto, and Akio Ojida. “Optimized Reaction Pair of the CysHis Tag and Ni(II)-NTA Probe for Highly Selective Chemical Labeling of Membrane Proteins.” Bulletin of the Chemical Society of Japan. Bulletin of the Chemical Society of Japan, 2019. https://doi.org/10.1246/bcsj.20190034.","mla":"Zenmyo, Naoki, et al. “Optimized Reaction Pair of the CysHis Tag and Ni(II)-NTA Probe for Highly Selective Chemical Labeling of Membrane Proteins.” Bulletin of the Chemical Society of Japan, vol. 92, no. 5, Bulletin of the Chemical Society of Japan, 2019, pp. 995–1000, doi:10.1246/bcsj.20190034.","short":"N. Zenmyo, H. Tokumaru, S. Uchinomiya, H. Fuchida, S. Tabata, I. Hamachi, R. Shigemoto, A. Ojida, Bulletin of the Chemical Society of Japan 92 (2019) 995–1000."},"article_type":"original","page":"995-1000","date_published":"2019-05-15T00:00:00Z"},{"has_accepted_license":"1","article_processing_charge":"No","day":"09","scopus_import":"1","date_published":"2019-09-09T00:00:00Z","citation":{"ama":"Byczkowicz N, Eshra A, Montanaro-Punzengruber J-C, et al. HCN channel-mediated neuromodulation can control action potential velocity and fidelity in central axons. eLife. 2019;8. doi:10.7554/eLife.42766","apa":"Byczkowicz, N., Eshra, A., Montanaro-Punzengruber, J.-C., Trevisiol, A., Hirrlinger, J., Kole, M. H., … Hallermann, S. (2019). HCN channel-mediated neuromodulation can control action potential velocity and fidelity in central axons. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.42766","ieee":"N. Byczkowicz et al., “HCN channel-mediated neuromodulation can control action potential velocity and fidelity in central axons,” eLife, vol. 8. eLife Sciences Publications, 2019.","ista":"Byczkowicz N, Eshra A, Montanaro-Punzengruber J-C, Trevisiol A, Hirrlinger J, Kole MH, Shigemoto R, Hallermann S. 2019. HCN channel-mediated neuromodulation can control action potential velocity and fidelity in central axons. eLife. 8, e42766.","short":"N. Byczkowicz, A. Eshra, J.-C. Montanaro-Punzengruber, A. Trevisiol, J. Hirrlinger, M.H. Kole, R. Shigemoto, S. Hallermann, ELife 8 (2019).","mla":"Byczkowicz, Niklas, et al. “HCN Channel-Mediated Neuromodulation Can Control Action Potential Velocity and Fidelity in Central Axons.” ELife, vol. 8, e42766, eLife Sciences Publications, 2019, doi:10.7554/eLife.42766.","chicago":"Byczkowicz, Niklas, Abdelmoneim Eshra, Jacqueline-Claire Montanaro-Punzengruber, Andrea Trevisiol, Johannes Hirrlinger, Maarten Hp Kole, Ryuichi Shigemoto, and Stefan Hallermann. “HCN Channel-Mediated Neuromodulation Can Control Action Potential Velocity and Fidelity in Central Axons.” ELife. eLife Sciences Publications, 2019. https://doi.org/10.7554/eLife.42766."},"publication":"eLife","article_type":"original","abstract":[{"text":"Hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels control electrical rhythmicity and excitability in the heart and brain, but the function of HCN channels at the subcellular level in axons remains poorly understood. Here, we show that the action potential conduction velocity in both myelinated and unmyelinated central axons can be bidirectionally modulated by a HCN channel blocker, cyclic adenosine monophosphate (cAMP), and neuromodulators. Recordings from mouse cerebellar mossy fiber boutons show that HCN channels ensure reliable high-frequency firing and are strongly modulated by cAMP (EC50 40 mM; estimated endogenous cAMP concentration 13 mM). In addition, immunogold-electron microscopy revealed HCN2 as the dominating subunit in cerebellar mossy fibers. Computational modeling indicated that HCN2 channels control conduction velocity primarily by altering the resting membrane potential\r\nand are associated with significant metabolic costs. These results suggest that the cAMP-HCN pathway provides neuromodulators with an opportunity to finely tune energy consumption and temporal delays across axons in the brain.","lang":"eng"}],"type":"journal_article","oa_version":"Published Version","file":[{"file_id":"6880","relation":"main_file","date_updated":"2020-07-14T12:47:42Z","date_created":"2019-09-16T13:14:33Z","checksum":"c350b7861ef0fb537cae8a3232aec016","file_name":"2019_eLife_Byczkowicz.pdf","access_level":"open_access","creator":"dernst","file_size":4008137,"content_type":"application/pdf"}],"_id":"6868","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","intvolume":" 8","status":"public","ddc":["570"],"title":"HCN channel-mediated neuromodulation can control action potential velocity and fidelity in central axons","publication_identifier":{"eissn":["2050084X"]},"month":"09","doi":"10.7554/eLife.42766","language":[{"iso":"eng"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"external_id":{"isi":["000485663900001"]},"isi":1,"quality_controlled":"1","file_date_updated":"2020-07-14T12:47:42Z","article_number":"e42766","author":[{"full_name":"Byczkowicz, Niklas","first_name":"Niklas","last_name":"Byczkowicz"},{"last_name":"Eshra","first_name":"Abdelmoneim","full_name":"Eshra, Abdelmoneim"},{"full_name":"Montanaro-Punzengruber, Jacqueline-Claire","last_name":"Montanaro-Punzengruber","first_name":"Jacqueline-Claire","id":"3786AB44-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Andrea","last_name":"Trevisiol","full_name":"Trevisiol, Andrea"},{"first_name":"Johannes","last_name":"Hirrlinger","full_name":"Hirrlinger, Johannes"},{"full_name":"Kole, Maarten Hp","last_name":"Kole","first_name":"Maarten Hp"},{"full_name":"Shigemoto, Ryuichi","orcid":"0000-0001-8761-9444","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","last_name":"Shigemoto","first_name":"Ryuichi"},{"last_name":"Hallermann","first_name":"Stefan","full_name":"Hallermann, Stefan"}],"volume":8,"date_created":"2019-09-15T22:00:43Z","date_updated":"2023-08-30T06:17:06Z","year":"2019","department":[{"_id":"RySh"}],"publisher":"eLife Sciences Publications","publication_status":"published"},{"publication_identifier":{"issn":["0896-6273"]},"month":"11","doi":"10.1016/j.neuron.2019.08.013","language":[{"iso":"eng"}],"external_id":{"isi":["000497963500017"],"pmid":["31543297"]},"oa":1,"main_file_link":[{"url":"https://doi.org/10.1016/j.neuron.2019.08.013","open_access":"1"}],"quality_controlled":"1","isi":1,"author":[{"full_name":"Kasugai, Yu","last_name":"Kasugai","first_name":"Yu"},{"first_name":"Elisabeth","last_name":"Vogel","full_name":"Vogel, Elisabeth"},{"full_name":"Hörtnagl, Heide","last_name":"Hörtnagl","first_name":"Heide"},{"first_name":"Sabine","last_name":"Schönherr","full_name":"Schönherr, Sabine"},{"first_name":"Enrica","last_name":"Paradiso","full_name":"Paradiso, Enrica"},{"last_name":"Hauschild","first_name":"Markus","full_name":"Hauschild, Markus"},{"first_name":"Georg","last_name":"Göbel","full_name":"Göbel, Georg"},{"full_name":"Milenkovic, Ivan","first_name":"Ivan","last_name":"Milenkovic"},{"full_name":"Peterschmitt, Yvan","last_name":"Peterschmitt","first_name":"Yvan"},{"full_name":"Tasan, Ramon","first_name":"Ramon","last_name":"Tasan"},{"full_name":"Sperk, Günther","last_name":"Sperk","first_name":"Günther"},{"full_name":"Shigemoto, Ryuichi","last_name":"Shigemoto","first_name":"Ryuichi","orcid":"0000-0001-8761-9444","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Sieghart, Werner","last_name":"Sieghart","first_name":"Werner"},{"first_name":"Nicolas","last_name":"Singewald","full_name":"Singewald, Nicolas"},{"last_name":"Lüthi","first_name":"Andreas","full_name":"Lüthi, Andreas"},{"last_name":"Ferraguti","first_name":"Francesco","full_name":"Ferraguti, Francesco"}],"volume":104,"date_created":"2019-11-25T08:02:39Z","date_updated":"2023-08-30T07:28:22Z","pmid":1,"acknowledgement":"The authors thank Gabi Schmid for excellent technical support. We also thank\r\nDr. H. Harada, Dr. W. Kaufmann, and Dr. B. Kapelari for testing the specificity\r\nof some of the antibodies used in this study on replicas. Funding was provided\r\nby the Austrian Science Fund (Fonds zur Fo¨ rderung der Wissenschaftlichen\r\nForschung) Sonderforschungsbereich grants F44-17 (to F.jF.), F44-10 and\r\nP25375-B24 (to N.S.), and P26680 (to G.S.) and by the Novartis Research\r\nFoundation and the Swiss National Science Foundation (to A.L). We also thank\r\nProf. M. Capogna for reading a previous version of the manuscript.","year":"2019","publisher":"Elsevier","department":[{"_id":"RySh"}],"publication_status":"published","article_processing_charge":"No","has_accepted_license":"1","day":"20","scopus_import":"1","date_published":"2019-11-20T00:00:00Z","citation":{"chicago":"Kasugai, Yu, Elisabeth Vogel, Heide Hörtnagl, Sabine Schönherr, Enrica Paradiso, Markus Hauschild, Georg Göbel, et al. “Structural and Functional Remodeling of Amygdala GABAergic Synapses in Associative Fear Learning.” Neuron. Elsevier, 2019. https://doi.org/10.1016/j.neuron.2019.08.013.","mla":"Kasugai, Yu, et al. “Structural and Functional Remodeling of Amygdala GABAergic Synapses in Associative Fear Learning.” Neuron, vol. 104, no. 4, Elsevier, 2019, p. 781–794.e4, doi:10.1016/j.neuron.2019.08.013.","short":"Y. Kasugai, E. Vogel, H. Hörtnagl, S. Schönherr, E. Paradiso, M. Hauschild, G. Göbel, I. Milenkovic, Y. Peterschmitt, R. Tasan, G. Sperk, R. Shigemoto, W. Sieghart, N. Singewald, A. Lüthi, F. Ferraguti, Neuron 104 (2019) 781–794.e4.","ista":"Kasugai Y, Vogel E, Hörtnagl H, Schönherr S, Paradiso E, Hauschild M, Göbel G, Milenkovic I, Peterschmitt Y, Tasan R, Sperk G, Shigemoto R, Sieghart W, Singewald N, Lüthi A, Ferraguti F. 2019. Structural and functional remodeling of amygdala GABAergic synapses in associative fear learning. Neuron. 104(4), 781–794.e4.","apa":"Kasugai, Y., Vogel, E., Hörtnagl, H., Schönherr, S., Paradiso, E., Hauschild, M., … Ferraguti, F. (2019). Structural and functional remodeling of amygdala GABAergic synapses in associative fear learning. Neuron. Elsevier. https://doi.org/10.1016/j.neuron.2019.08.013","ieee":"Y. Kasugai et al., “Structural and functional remodeling of amygdala GABAergic synapses in associative fear learning,” Neuron, vol. 104, no. 4. Elsevier, p. 781–794.e4, 2019.","ama":"Kasugai Y, Vogel E, Hörtnagl H, et al. Structural and functional remodeling of amygdala GABAergic synapses in associative fear learning. Neuron. 2019;104(4):781-794.e4. doi:10.1016/j.neuron.2019.08.013"},"publication":"Neuron","page":"781-794.e4","article_type":"original","issue":"4","type":"journal_article","oa_version":"Published Version","_id":"7099","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","intvolume":" 104","ddc":["571","599"],"title":"Structural and functional remodeling of amygdala GABAergic synapses in associative fear learning","status":"public"}]