[{"status":"public","type":"journal_article","article_type":"original","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"_id":"10890","file_date_updated":"2022-03-21T09:41:19Z","department":[{"_id":"RySh"}],"ddc":["570"],"date_updated":"2023-08-03T06:07:18Z","month":"02","intvolume":" 16","scopus_import":"1","pmid":1,"oa_version":"Published Version","abstract":[{"lang":"eng","text":"Upon the arrival of action potentials at nerve terminals, neurotransmitters are released from synaptic vesicles (SVs) by exocytosis. CaV2.1, 2.2, and 2.3 are the major subunits of the voltage-gated calcium channel (VGCC) responsible for increasing intraterminal calcium levels and triggering SV exocytosis in the central nervous system (CNS) synapses. The two-dimensional analysis of CaV2 distributions using sodium dodecyl sulfate (SDS)-digested freeze-fracture replica labeling (SDS-FRL) has revealed their numbers, densities, and nanoscale clustering patterns in individual presynaptic active zones. The variation in these properties affects the coupling of VGCCs with calcium sensors on SVs, synaptic efficacy, and temporal precision of transmission. In this study, we summarize how the morphological parameters of CaV2 distribution obtained using SDS-FRL differ depending on the different types of synapses and could correspond to functional properties in synaptic transmission."}],"volume":16,"ec_funded":1,"file":[{"success":1,"checksum":"51ec9b90e7da919e22c01a15489eaacd","file_id":"10911","relation":"main_file","access_level":"open_access","content_type":"application/pdf","file_name":"2022_FrontiersNeuroanatomy_Eguchi.pdf","date_created":"2022-03-21T09:41:19Z","creator":"dernst","file_size":2416395,"date_updated":"2022-03-21T09:41:19Z"}],"language":[{"iso":"eng"}],"publication_identifier":{"eissn":["16625129"]},"publication_status":"published","project":[{"grant_number":"694539","name":"In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour","call_identifier":"H2020","_id":"25CA28EA-B435-11E9-9278-68D0E5697425"},{"_id":"05970B30-7A3F-11EA-A408-12923DDC885E","grant_number":"I04638","name":"LGI1 antibody-induced pathophysiology in synapses"}],"article_number":"846615","title":"The number and distinct clustering patterns of voltage-gated Calcium channels in nerve terminals","author":[{"id":"2B7846DC-F248-11E8-B48F-1D18A9856A87","first_name":"Kohgaku","orcid":"0000-0002-6170-2546","full_name":"Eguchi, Kohgaku","last_name":"Eguchi"},{"id":"3786AB44-F248-11E8-B48F-1D18A9856A87","first_name":"Jacqueline-Claire","full_name":"Montanaro-Punzengruber, Jacqueline-Claire","last_name":"Montanaro-Punzengruber"},{"last_name":"Le Monnier","full_name":"Le Monnier, Elodie","id":"3B59276A-F248-11E8-B48F-1D18A9856A87","first_name":"Elodie"},{"orcid":"0000-0001-8761-9444","full_name":"Shigemoto, Ryuichi","last_name":"Shigemoto","first_name":"Ryuichi","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87"}],"external_id":{"pmid":["35280978"],"isi":["000766662700001"]},"article_processing_charge":"No","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"chicago":"Eguchi, Kohgaku, Jacqueline-Claire Montanaro-Punzengruber, Elodie Le Monnier, and Ryuichi Shigemoto. “The Number and Distinct Clustering Patterns of Voltage-Gated Calcium Channels in Nerve Terminals.” Frontiers in Neuroanatomy. Frontiers, 2022. https://doi.org/10.3389/fnana.2022.846615.","ista":"Eguchi K, Montanaro-Punzengruber J-C, Le Monnier E, Shigemoto R. 2022. The number and distinct clustering patterns of voltage-gated Calcium channels in nerve terminals. Frontiers in Neuroanatomy. 16, 846615.","mla":"Eguchi, Kohgaku, et al. “The Number and Distinct Clustering Patterns of Voltage-Gated Calcium Channels in Nerve Terminals.” Frontiers in Neuroanatomy, vol. 16, 846615, Frontiers, 2022, doi:10.3389/fnana.2022.846615.","ieee":"K. Eguchi, J.-C. Montanaro-Punzengruber, E. Le Monnier, and R. Shigemoto, “The number and distinct clustering patterns of voltage-gated Calcium channels in nerve terminals,” Frontiers in Neuroanatomy, vol. 16. Frontiers, 2022.","short":"K. Eguchi, J.-C. Montanaro-Punzengruber, E. Le Monnier, R. Shigemoto, Frontiers in Neuroanatomy 16 (2022).","ama":"Eguchi K, Montanaro-Punzengruber J-C, Le Monnier E, Shigemoto R. The number and distinct clustering patterns of voltage-gated Calcium channels in nerve terminals. Frontiers in Neuroanatomy. 2022;16. doi:10.3389/fnana.2022.846615","apa":"Eguchi, K., Montanaro-Punzengruber, J.-C., Le Monnier, E., & Shigemoto, R. (2022). The number and distinct clustering patterns of voltage-gated Calcium channels in nerve terminals. Frontiers in Neuroanatomy. Frontiers. https://doi.org/10.3389/fnana.2022.846615"},"publisher":"Frontiers","quality_controlled":"1","oa":1,"acknowledgement":"This work was supported by the European Research Council advanced grant No. 694539 and the joint German-Austrian DFG and FWF project SYNABS (FWF: I-4638-B) to RS.\r\nThe authors thank Walter Kaufmann for his critical comments on the manuscript.","date_published":"2022-02-24T00:00:00Z","doi":"10.3389/fnana.2022.846615","date_created":"2022-03-20T23:01:39Z","day":"24","publication":"Frontiers in Neuroanatomy","isi":1,"has_accepted_license":"1","year":"2022"},{"project":[{"name":"In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour","grant_number":"694539","call_identifier":"H2020","_id":"25CA28EA-B435-11E9-9278-68D0E5697425"},{"grant_number":"692692","name":"Biophysics and circuit function of a giant cortical glumatergic synapse","call_identifier":"H2020","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425"},{"_id":"2564DBCA-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"665385","name":"International IST Doctoral Program"}],"article_number":"e68274","author":[{"first_name":"Pradeep","id":"45EDD1BC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-0863-4481","full_name":"Bhandari, Pradeep","last_name":"Bhandari"},{"id":"3AE48E0A-F248-11E8-B48F-1D18A9856A87","first_name":"David H","last_name":"Vandael","full_name":"Vandael, David H","orcid":"0000-0001-7577-1676"},{"last_name":"Fernández-Fernández","full_name":"Fernández-Fernández, Diego","first_name":"Diego"},{"first_name":"Thorsten","full_name":"Fritzius, Thorsten","last_name":"Fritzius"},{"first_name":"David","id":"42E121A4-F248-11E8-B48F-1D18A9856A87","full_name":"Kleindienst, David","last_name":"Kleindienst"},{"first_name":"Hüseyin C","id":"4659D740-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-2771-2011","full_name":"Önal, Hüseyin C","last_name":"Önal"},{"last_name":"Montanaro-Punzengruber","full_name":"Montanaro-Punzengruber, Jacqueline-Claire","first_name":"Jacqueline-Claire","id":"3786AB44-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Martin","last_name":"Gassmann","full_name":"Gassmann, Martin"},{"full_name":"Jonas, Peter M","orcid":"0000-0001-5001-4804","last_name":"Jonas","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","first_name":"Peter M"},{"last_name":"Kulik","full_name":"Kulik, Akos","first_name":"Akos"},{"full_name":"Bettler, Bernhard","last_name":"Bettler","first_name":"Bernhard"},{"first_name":"Ryuichi","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","last_name":"Shigemoto","full_name":"Shigemoto, Ryuichi","orcid":"0000-0001-8761-9444"},{"first_name":"Peter","id":"3B8B25A8-F248-11E8-B48F-1D18A9856A87","last_name":"Koppensteiner","orcid":"0000-0002-3509-1948","full_name":"Koppensteiner, Peter"}],"article_processing_charge":"No","external_id":{"isi":["000651761700001"]},"title":"GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals","citation":{"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.","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).","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.","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"},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","quality_controlled":"1","publisher":"eLife Sciences Publications","oa":1,"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.","date_published":"2021-04-29T00:00:00Z","doi":"10.7554/ELIFE.68274","date_created":"2021-05-30T22:01:23Z","isi":1,"has_accepted_license":"1","year":"2021","day":"29","publication":"eLife","article_type":"original","type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"status":"public","_id":"9437","file_date_updated":"2021-05-31T09:43:09Z","department":[{"_id":"RySh"},{"_id":"PeJo"}],"date_updated":"2024-03-27T23:30:30Z","ddc":["570"],"scopus_import":"1","month":"04","intvolume":" 10","abstract":[{"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.","lang":"eng"}],"oa_version":"Published Version","volume":10,"related_material":{"link":[{"relation":"earlier_version","url":"https://doi.org/10.1101/2020.04.16.045112"}],"record":[{"status":"public","id":"9562","relation":"dissertation_contains"}]},"ec_funded":1,"publication_identifier":{"eissn":["2050-084X"]},"publication_status":"published","file":[{"relation":"main_file","access_level":"open_access","content_type":"application/pdf","success":1,"file_id":"9440","checksum":"6ebcb79999f889766f7cd79ee134ad28","creator":"cziletti","file_size":8174719,"date_updated":"2021-05-31T09:43:09Z","file_name":"2021_eLife_Bhandari.pdf","date_created":"2021-05-31T09:43:09Z"}],"language":[{"iso":"eng"}]},{"_id":"8532","status":"public","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"type":"journal_article","article_type":"original","ddc":["570"],"date_updated":"2024-03-27T23:30:30Z","file_date_updated":"2020-09-21T14:08:58Z","department":[{"_id":"RySh"}],"oa_version":"Published Version","abstract":[{"lang":"eng","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."}],"intvolume":" 21","month":"09","scopus_import":"1","language":[{"iso":"eng"}],"file":[{"date_created":"2020-09-21T14:08:58Z","file_name":"2020_JournMolecSciences_Kleindienst.pdf","date_updated":"2020-09-21T14:08:58Z","file_size":5748456,"creator":"dernst","file_id":"8551","checksum":"2e4f62f3cfe945b7391fc3070e5a289f","success":1,"content_type":"application/pdf","access_level":"open_access","relation":"main_file"}],"publication_status":"published","publication_identifier":{"issn":["16616596"],"eissn":["14220067"]},"ec_funded":1,"volume":21,"related_material":{"record":[{"id":"9562","status":"public","relation":"dissertation_contains"}]},"issue":"18","article_number":"6737","project":[{"name":"In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour","grant_number":"694539","call_identifier":"H2020","_id":"25CA28EA-B435-11E9-9278-68D0E5697425"},{"name":"Mechanism of formation and maintenance of input side-dependent asymmetry in the hippocampus","_id":"25D32BC0-B435-11E9-9278-68D0E5697425"},{"name":"Human Brain Project Specific Grant Agreement 2 (HBP SGA 2)","grant_number":"785907","call_identifier":"H2020","_id":"26436750-B435-11E9-9278-68D0E5697425"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"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.","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.","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.","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","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","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.","short":"D. Kleindienst, J.-C. Montanaro-Punzengruber, P. Bhandari, M.J. Case, Y. Fukazawa, R. Shigemoto, International Journal of Molecular Sciences 21 (2020)."},"title":"Deep learning-assisted high-throughput analysis of freeze-fracture replica images applied to glutamate receptors and calcium channels at hippocampal synapses","external_id":{"isi":["000579945300001"]},"article_processing_charge":"No","author":[{"last_name":"Kleindienst","full_name":"Kleindienst, David","id":"42E121A4-F248-11E8-B48F-1D18A9856A87","first_name":"David"},{"last_name":"Montanaro-Punzengruber","full_name":"Montanaro-Punzengruber, Jacqueline-Claire","id":"3786AB44-F248-11E8-B48F-1D18A9856A87","first_name":"Jacqueline-Claire"},{"first_name":"Pradeep","id":"45EDD1BC-F248-11E8-B48F-1D18A9856A87","last_name":"Bhandari","full_name":"Bhandari, Pradeep","orcid":"0000-0003-0863-4481"},{"first_name":"Matthew J","id":"44B7CA5A-F248-11E8-B48F-1D18A9856A87","last_name":"Case","full_name":"Case, Matthew J"},{"last_name":"Fukazawa","full_name":"Fukazawa, Yugo","first_name":"Yugo"},{"orcid":"0000-0001-8761-9444","full_name":"Shigemoto, Ryuichi","last_name":"Shigemoto","first_name":"Ryuichi","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87"}],"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.","oa":1,"publisher":"MDPI","quality_controlled":"1","publication":"International Journal of Molecular Sciences","day":"14","year":"2020","isi":1,"has_accepted_license":"1","date_created":"2020-09-20T22:01:35Z","date_published":"2020-09-14T00:00:00Z","doi":"10.3390/ijms21186737"},{"author":[{"first_name":"Niklas","full_name":"Byczkowicz, Niklas","last_name":"Byczkowicz"},{"first_name":"Abdelmoneim","full_name":"Eshra, Abdelmoneim","last_name":"Eshra"},{"id":"3786AB44-F248-11E8-B48F-1D18A9856A87","first_name":"Jacqueline-Claire","full_name":"Montanaro-Punzengruber, Jacqueline-Claire","last_name":"Montanaro-Punzengruber"},{"full_name":"Trevisiol, Andrea","last_name":"Trevisiol","first_name":"Andrea"},{"first_name":"Johannes","full_name":"Hirrlinger, Johannes","last_name":"Hirrlinger"},{"first_name":"Maarten Hp","last_name":"Kole","full_name":"Kole, Maarten Hp"},{"id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","first_name":"Ryuichi","orcid":"0000-0001-8761-9444","full_name":"Shigemoto, Ryuichi","last_name":"Shigemoto"},{"first_name":"Stefan","last_name":"Hallermann","full_name":"Hallermann, Stefan"}],"external_id":{"isi":["000485663900001"]},"article_processing_charge":"No","title":"HCN channel-mediated neuromodulation can control action potential velocity and fidelity in central axons","citation":{"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.","short":"N. Byczkowicz, A. Eshra, J.-C. Montanaro-Punzengruber, A. Trevisiol, J. Hirrlinger, M.H. Kole, R. Shigemoto, S. Hallermann, ELife 8 (2019).","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.","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","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","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.","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."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","article_number":"e42766","doi":"10.7554/eLife.42766","date_published":"2019-09-09T00:00:00Z","date_created":"2019-09-15T22:00:43Z","isi":1,"has_accepted_license":"1","year":"2019","day":"09","publication":"eLife","publisher":"eLife Sciences Publications","quality_controlled":"1","oa":1,"department":[{"_id":"RySh"}],"file_date_updated":"2020-07-14T12:47:42Z","date_updated":"2023-08-30T06:17:06Z","ddc":["570"],"type":"journal_article","article_type":"original","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"status":"public","_id":"6868","volume":8,"publication_identifier":{"eissn":["2050084X"]},"publication_status":"published","file":[{"checksum":"c350b7861ef0fb537cae8a3232aec016","file_id":"6880","content_type":"application/pdf","relation":"main_file","access_level":"open_access","file_name":"2019_eLife_Byczkowicz.pdf","date_created":"2019-09-16T13:14:33Z","file_size":4008137,"date_updated":"2020-07-14T12:47:42Z","creator":"dernst"}],"language":[{"iso":"eng"}],"scopus_import":"1","month":"09","intvolume":" 8","abstract":[{"lang":"eng","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."}],"oa_version":"Published Version"}]