Input-specific regulation of glutamatergic synaptic transmission in the medial prefrontal cortex by mGlu 2 /mGlu 4 receptor heterodimers
- 6 April 2021
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science Signaling
- Vol. 14 (677)
- https://doi.org/10.1126/scisignal.abd2319
Abstract
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.Keywords
Funding Information
- National Institute of Mental Health (MH108498)
- National Institute of Mental Health (MH108498)
- National Institute of Neurological Disorders and Stroke (NS031373)
- National Institute of Health (NS031373)
- National Institute of Health (MH108498)
- National Institute of Health (R21NS113614)
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