An unsuspected physiological role for mGluRIII glutamate receptors in hippocampal area CA1

Abstract

Group III metabotropic glutamate receptors (mGluRIII) are expressed broadly throughout the hippocampus but are thought to inhibit neurotransmitter release only at a subset of synapses and in a target-cell-specific manner. Here, we show that the supposed target-cell-specific modulation of GABA release only occurs when the extracellular calcium concentration in the recording solution is higher than its physiological value. Lowering extracellular calcium reveals an unsuspected mGluRIII-dependent suppression of inhibition onto CA1 pyramidal cells. This effect is due to a reduction in the size of the readily releasable pool, mediated by protein kinase A, and its vesicle-associated target proteins, synapsins. Using in vivo whole-cell recordings in behaving mice, we show that reducing spillover or blocking mGluRIII receptors in the intact CA1 network disrupts CA1 place cell activity. Together, these findings challenge our current understanding of the role of mGluRIII receptors in mediating hippocampal synaptic transmission and encoding spatial information.