Input-specific regulation of glutamatergic synaptic transmission in the medial prefrontal cortex by mGlu2/mGlu4 receptor heterodimers
Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works..
Metabotropic glutamate receptors (mGluRs) are G protein-coupled receptors that regulate various aspects of central nervous system processing in normal physiology and in disease. They are thought to function as disulfide-linked homodimers, but studies have suggested that mGluRs can form functional heterodimers in cell lines. Using selective allosteric ligands, ex vivo brain slice electrophysiology, and optogenetic approaches, we found that two mGluR subtypes-mGluR2 and mGluR4 (or mGlu2 and mGlu4)-exist as functional heterodimers that regulate excitatory transmission in a synapse-specific manner within the rodent medial prefrontal cortex (mPFC). Activation of mGlu2/mGlu4 heterodimers inhibited glutamatergic signaling at thalamo-mPFC synapses but not at hippocampus-mPFC or amygdala-mPFC synapses. These findings raise the possibility that selectively targeting these heterodimers could be a therapeutic strategy for some neurologic and neuropsychiatric disorders involving specific brain circuits.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
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| Enthalten in: |
Science signaling - 14(2021), 677 vom: 06. Apr. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Xiang, Zixiu [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 13.01.2022 Date Revised 24.02.2022 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1126/scisignal.abd2319 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM323794882 |
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| 500 | |a Date Revised 24.02.2022 | ||
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. | ||
| 520 | |a Metabotropic glutamate receptors (mGluRs) are G protein-coupled receptors that regulate various aspects of central nervous system processing in normal physiology and in disease. They are thought to function as disulfide-linked homodimers, but studies have suggested that mGluRs can form functional heterodimers in cell lines. Using selective allosteric ligands, ex vivo brain slice electrophysiology, and optogenetic approaches, we found that two mGluR subtypes-mGluR2 and mGluR4 (or mGlu2 and mGlu4)-exist as functional heterodimers that regulate excitatory transmission in a synapse-specific manner within the rodent medial prefrontal cortex (mPFC). Activation of mGlu2/mGlu4 heterodimers inhibited glutamatergic signaling at thalamo-mPFC synapses but not at hippocampus-mPFC or amygdala-mPFC synapses. These findings raise the possibility that selectively targeting these heterodimers could be a therapeutic strategy for some neurologic and neuropsychiatric disorders involving specific brain circuits | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 700 | 1 | |a Lv, Xiaohui |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Xin |e verfasserin |4 aut | |
| 700 | 1 | |a O'Brien, Daniel E |e verfasserin |4 aut | |
| 700 | 1 | |a Altman, Molly K |e verfasserin |4 aut | |
| 700 | 1 | |a Lindsley, Craig W |e verfasserin |4 aut | |
| 700 | 1 | |a Javitch, Jonathan A |e verfasserin |4 aut | |
| 700 | 1 | |a Niswender, Colleen M |e verfasserin |4 aut | |
| 700 | 1 | |a Conn, P Jeffrey |e verfasserin |4 aut | |
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