Differential distribution and function of GABABRs in somato-dendritic and axonal compartments of principal cells and interneurons in cortical circuits

Abstract

GABA_BRs are highly expressed in cortical circuits, controlling neuronal excitability and synaptic transmission in both principal cells and inhibitory interneurons. Light and electron microscopic studies confirmed the wide distribution of receptors and revealed cell type-specific quantitative differences in their cellular and subcellular distributions. At the subcellular level, GABA_BRs are abundant at the peri- and extrasynaptic membrane of somato-dendritic compartments and to lower levels in the axon terminals of both cortical excitatory principal cells and inhibitory interneurons. Differences in the surface densities are particularly prominent between neurochemically-defined interneuron types. Whole-cell recordings further demonstrated that GABA_BRs differentially mediate post- and presynaptic inhibition in principal cells and various GABAergic interneurons by preferentially modulating postsynaptic G-protein-coupled inwardly rectifying K⁺ (Kir3) channels and presynaptic high voltage-activated Ca²⁺ (Ca_v) channels. These data convergently indicate that GABA_BRs not only control the overall level of neuronal excitability and activity, but can also fine tune the activation and interactions of excitatory and inhibitory neurons in cortical circuits. This article is part of the "Special Issue Dedicated to Norman G. Bowery".

Keywords: Dendritic inhibition; Electron microscopy; Ion channels; Network activity; Presynaptic inhibition; Synaptic plasticity.