Mechanisms of mGluR-dependent plasticity in hippocampal area CA2
dc.contributor.author | Samadi, Mahsa | en |
dc.contributor.author | Hales, Claire A. | en |
dc.contributor.author | Lustberg, Daniel J. | en |
dc.contributor.author | Farris, Shannon | en |
dc.contributor.author | Ross, Madeleine R. | en |
dc.contributor.author | Zhao, Meilan | en |
dc.contributor.author | Hepler, John R. | en |
dc.contributor.author | Harbin, Nicholas H. | en |
dc.contributor.author | Robinson, Emma S. J. | en |
dc.contributor.author | Banks, Paul J. | en |
dc.contributor.author | Bashir, Zafar I. | en |
dc.contributor.author | Dudek, Serena M. | en |
dc.date.accessioned | 2023-10-06T12:49:34Z | en |
dc.date.available | 2023-10-06T12:49:34Z | en |
dc.date.issued | 2023-06 | en |
dc.description.abstract | Pyramidal cells in hippocampal area CA2 have synaptic properties that are distinct from the other CA subregions. Notably, this includes a lack of typical long-term potentiation of stratum radiatum synapses. CA2 neurons express high levels of several known and potential regulators of metabotropic glutamate receptor (mGluR)-dependent signaling including Striatal-Enriched Tyrosine Phosphatase (STEP) and several Regulator of G-protein Signaling (RGS) proteins, yet the functions of these proteins in regulating mGluR-dependent synaptic plasticity in CA2 are completely unknown. Thus, the aim of this study was to examine mGluR-dependent synaptic depression and to determine whether STEP and the RGS proteins RGS4 and RGS14 are involved. Using whole cell voltage-clamp recordings from mouse pyramidal cells, we found that mGluR agonist-induced long-term depression (mGluR-LTD) is more pronounced in CA2 compared with that observed in CA1. This mGluR-LTD in CA2 was found to be protein synthesis and STEP dependent, suggesting that CA2 mGluR-LTD shares mechanistic processes with those seen in CA1, but in addition, RGS14, but not RGS4, was essential for mGluR-LTD in CA2. In addition, we found that exogenous application of STEP could rescue mGluR-LTD in RGS14 KO slices. Supporting a role for CA2 synaptic plasticity in social cognition, we found that RGS14 KO mice had impaired social recognition memory as assessed in a social discrimination task. These results highlight possible roles for mGluRs, RGS14, and STEP in CA2-dependent behaviors, perhaps by biasing the dominant form of synaptic plasticity away from LTP and toward LTD in CA2. | en |
dc.description.notes | National Institute of Environmental Health Sciences; US National Institutes of Health,Grant/Award Number: ES 100221; Wellcome Trust Investigator Award, Grant/AwardNumber: 206401/Z/17/Z; Wellcome Trust-NIH PhD Studentship, Grant/Award Number:100941/Z/13/Z | en |
dc.description.sponsorship | National Institute of Environmental Health Sciences; US National Institutes of Health [ES 100221]; Wellcome Trust Investigator Award [206401/Z/17/Z]; Wellcome Trust-NIH PhD Studentship [100941/Z/13/Z] | en |
dc.description.version | Published version | en |
dc.format.mimetype | application/pdf | en |
dc.identifier.doi | https://doi.org/10.1002/hipo.23529 | en |
dc.identifier.eissn | 1098-1063 | en |
dc.identifier.issn | 1050-9631 | en |
dc.identifier.issue | 6 | en |
dc.identifier.pmid | 36971428 | en |
dc.identifier.uri | http://hdl.handle.net/10919/116417 | en |
dc.identifier.volume | 33 | en |
dc.language.iso | en | en |
dc.publisher | Wiley | en |
dc.rights | Creative Commons Attribution 4.0 International | en |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en |
dc.subject | hippocampus | en |
dc.subject | long-term depression | en |
dc.subject | RGS14 | en |
dc.subject | social recognition memory | en |
dc.subject | synaptic plasticity | en |
dc.title | Mechanisms of mGluR-dependent plasticity in hippocampal area CA2 | en |
dc.title.serial | Hippocampus | en |
dc.type | Article - Refereed | en |
dc.type.dcmitype | Text | en |
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