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Fast synaptic neurotransmission in the vertebrate central nervous system relies primarily on ionotropic glutamate receptors (iGluRs), that drive neuronal excitation, and type A γ-aminobutyric acid receptors (GABAARs), responsible for neuronal inhibition. However, the GluD1 receptor, an iGluR family member, is present at both excitatory and inhibitory synapses. Whether and how GluD1 activation may impact inhibitory neurotransmission is unknown. Here, using a combination of biochemical, structural and functional analyses, we demonstrate that GluD1 binds GABA, an unprecedented feature for iGluRs. GluD1 activation produces long-lasting enhancement of GABAergic synaptic currents in the adult mouse hippocampus through a non-ionotropic mechanism dependent on trans-synaptic anchoring. The identification of GluD1 as a GABA receptor that controls inhibitory synaptic plasticity challenges the classical dichotomy between glutamatergic and GABAergic receptors.

Original publication

DOI

10.1126/science.adf3406

Type

Journal article

Journal

Science (New York, N.Y.)

Publication Date

12/2023

Addresses

Institut de Biologie de l'ENS (IBENS), Ecole Normale Supérieure, Université PSL, CNRS, INSERM, F-75005 Paris, France.