RGS7/Gβ5/R7BP complex regulates synaptic plasticity and memory by modulating hippocampal GABABR-GIRK signaling
In the hippocampus, the inhibitory neurotransmitter GABA shapes the activity of the output pyramidal neurons and plays important role in cognition. Most of its inhibitory effects are mediated by signaling from GABAB receptor to the G protein-gated Inwardly-rectifying K+ (GIRK) channels. Here, we sho...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2014-04-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/02053 |
| _version_ | 1811235914032087040 |
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| author | Olga Ostrovskaya Keqiang Xie Ikuo Masuho Ana Fajardo-Serrano Rafael Lujan Kevin Wickman Kirill A Martemyanov |
| author_facet | Olga Ostrovskaya Keqiang Xie Ikuo Masuho Ana Fajardo-Serrano Rafael Lujan Kevin Wickman Kirill A Martemyanov |
| author_sort | Olga Ostrovskaya |
| collection | DOAJ |
| description | In the hippocampus, the inhibitory neurotransmitter GABA shapes the activity of the output pyramidal neurons and plays important role in cognition. Most of its inhibitory effects are mediated by signaling from GABAB receptor to the G protein-gated Inwardly-rectifying K+ (GIRK) channels. Here, we show that RGS7, in cooperation with its binding partner R7BP, regulates GABABR-GIRK signaling in hippocampal pyramidal neurons. Deletion of RGS7 in mice dramatically sensitizes GIRK responses to GABAB receptor stimulation and markedly slows channel deactivation kinetics. Enhanced activity of this signaling pathway leads to decreased neuronal excitability and selective disruption of inhibitory forms of synaptic plasticity. As a result, mice lacking RGS7 exhibit deficits in learning and memory. We further report that RGS7 is selectively modulated by its membrane anchoring subunit R7BP, which sets the dynamic range of GIRK responses. Together, these results demonstrate a novel role of RGS7 in hippocampal synaptic plasticity and memory formation. |
| first_indexed | 2024-04-12T12:00:00Z |
| format | Article |
| id | doaj.art-26a4c6c2228340209a082f8399ea1309 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T12:00:00Z |
| publishDate | 2014-04-01 |
| publisher | eLife Sciences Publications Ltd |
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| spelling | doaj.art-26a4c6c2228340209a082f8399ea13092022-12-22T03:33:53ZengeLife Sciences Publications LtdeLife2050-084X2014-04-01310.7554/eLife.02053RGS7/Gβ5/R7BP complex regulates synaptic plasticity and memory by modulating hippocampal GABABR-GIRK signalingOlga Ostrovskaya0Keqiang Xie1Ikuo Masuho2Ana Fajardo-Serrano3Rafael Lujan4Kevin Wickman5Kirill A Martemyanov6Department of Neuroscience, The Scripps Research Institute, Jupiter, United StatesDepartment of Neuroscience, The Scripps Research Institute, Jupiter, United StatesDepartment of Neuroscience, The Scripps Research Institute, Jupiter, United StatesDepartamento de Ciencias Médicas, Facultad de Medicina, Universidad de Castilla-La Mancha, Albacete, SpainDepartamento de Ciencias Médicas, Facultad de Medicina, Universidad de Castilla-La Mancha, Albacete, SpainDepartment of Pharmacology, University of Minnesota, Minneapolis, United StatesDepartment of Neuroscience, The Scripps Research Institute, Jupiter, United StatesIn the hippocampus, the inhibitory neurotransmitter GABA shapes the activity of the output pyramidal neurons and plays important role in cognition. Most of its inhibitory effects are mediated by signaling from GABAB receptor to the G protein-gated Inwardly-rectifying K+ (GIRK) channels. Here, we show that RGS7, in cooperation with its binding partner R7BP, regulates GABABR-GIRK signaling in hippocampal pyramidal neurons. Deletion of RGS7 in mice dramatically sensitizes GIRK responses to GABAB receptor stimulation and markedly slows channel deactivation kinetics. Enhanced activity of this signaling pathway leads to decreased neuronal excitability and selective disruption of inhibitory forms of synaptic plasticity. As a result, mice lacking RGS7 exhibit deficits in learning and memory. We further report that RGS7 is selectively modulated by its membrane anchoring subunit R7BP, which sets the dynamic range of GIRK responses. Together, these results demonstrate a novel role of RGS7 in hippocampal synaptic plasticity and memory formation.https://elifesciences.org/articles/02053GPCR signalingRGS proteinsynaptic plasticitylearning and memoryhippocampusGIRK channel |
| spellingShingle | Olga Ostrovskaya Keqiang Xie Ikuo Masuho Ana Fajardo-Serrano Rafael Lujan Kevin Wickman Kirill A Martemyanov RGS7/Gβ5/R7BP complex regulates synaptic plasticity and memory by modulating hippocampal GABABR-GIRK signaling eLife GPCR signaling RGS protein synaptic plasticity learning and memory hippocampus GIRK channel |
| title | RGS7/Gβ5/R7BP complex regulates synaptic plasticity and memory by modulating hippocampal GABABR-GIRK signaling |
| title_full | RGS7/Gβ5/R7BP complex regulates synaptic plasticity and memory by modulating hippocampal GABABR-GIRK signaling |
| title_fullStr | RGS7/Gβ5/R7BP complex regulates synaptic plasticity and memory by modulating hippocampal GABABR-GIRK signaling |
| title_full_unstemmed | RGS7/Gβ5/R7BP complex regulates synaptic plasticity and memory by modulating hippocampal GABABR-GIRK signaling |
| title_short | RGS7/Gβ5/R7BP complex regulates synaptic plasticity and memory by modulating hippocampal GABABR-GIRK signaling |
| title_sort | rgs7 gβ5 r7bp complex regulates synaptic plasticity and memory by modulating hippocampal gababr girk signaling |
| topic | GPCR signaling RGS protein synaptic plasticity learning and memory hippocampus GIRK channel |
| url | https://elifesciences.org/articles/02053 |
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