Postsynaptic GABABRs Inhibit L-Type Calcium Channels and Abolish Long-Term Potentiation in Hippocampal Somatostatin Interneurons

Abstract

Inhibition provided by local GABAergic interneurons (INs) activates ionotropic GABA_A and metabotropic GABA_B receptors (GABA_BRs). Despite GABA_BRs representing a major source of inhibition, little is known of their function in distinct IN subtypes. Here, we show that, while the archetypal dendritic-inhibitory somatostatin-expressing INs (SOM-INs) possess high levels of GABA_BR on their somato-dendritic surface, they fail to produce significant postsynaptic inhibitory currents. Instead, GABA_BRs selectively inhibit dendritic Ca_V1.2 (L-type) Ca²⁺ channels on SOM-IN dendrites, leading to reduced calcium influx and loss of long-term potentiation at excitatory input synapses onto these INs. These data provide a mechanism by which GABA_BRs can contribute to disinhibition and control the efficacy of extrinsic inputs to hippocampal networks.

Keywords: Cav1.2 channels; GABA(B) receptors; GABAergic interneurons; dendrites; electron microscopy; feedback inhibition; hippocampus; multi-photon imaging; synaptic plasticity; whole-cell recording.