GABAB receptor-mediated modulation of metabotropic glutamate signaling and synaptic plasticity in central neurons.
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 including cerebellar long-term depression, a form of synaptic plasticity crucial for cerebellar motor learning. In this article, we present current knowledge on a new role of GABA(B)R as an ambience-dependent regulator of synaptic signaling.
Tabata
Toshihide
T
Laboratory for Neural Information Technology, Graduate School of Sciences and Engineering, University of Toyama, Toyama, Japan.
Kano
Masanobu
M
D000818:Animals; D002490:Central Nervous System / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000378:metabolism*; D018080:Receptors, GABA-B / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D015398:Signal Transduction; D013569:Synapses / Q000378:metabolism*
D018080:Receptors, GABA-B; D018094:Receptors, Metabotropic Glutamate