GABAB receptor-mediated modulation of metabotropic glutamate signaling and synaptic plasticity in central neurons

Advances in Pharmacology
Toshihide Tabata, Masanobu Kano

Abstract

In mammalian brains, gamma-amino butyric acid (GABA) is the most ubiquitous inhibitory neurotransmitter and neuromodulator. The G(i/o) protein-coupled GABA receptor termed B-type GABA receptor (GABA(B)R) has been recognized as one of the major mediators of the inhibitory effects of GABA. Several years ago, Hirono et al. and our group independently found that GABA(B)R mediates non-inhibitory effects in cerebellar Purkinje cells. In this cell type, GABA(B)R co-localizes with type-1 metabotropic glutamate receptor (mGluR1), a G(q/11) protein-coupled receptor around the postsynaptic membrane of the excitatory synapses. At that site, GABA(B)R is not exposed to the direct bombardment of GABA released from the terminals of inhibitory neurons. Instead, the receptor may sense a low concentration of GABA and Ca(2+) usually contained in the extracellular fluid and a relatively high concentration of GABA spilt over from the neighboring active inhibitory synapses. In response to these ambient ligands, GABA(B)R increases the ligand affinity of mGluR1 independently of G(i/o) protein and augments mGluR1-coupled intracellular signaling via G(i/o) protein. These GABA(B)R-mediated modulations may facilitate mGluR1-mediated neuronal responses incl...Continue Reading

Citations

Jan 14, 2011·Behavior Genetics·Dean PalejevElena L Grigorenko
Jun 2, 2018·Applied Physiology, Nutrition, and Metabolism = Physiologie Appliquée, Nutrition Et Métabolisme·Christopher W MacDonell, Phillip F Gardiner
Nov 25, 2020·Neurobiology of Aging·Arnold M SalazarJefferson W Kinney

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