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

Cell Rep. 2018 Jan 2;22(1):36-43. doi: 10.1016/j.celrep.2017.12.021.

Abstract

Inhibition provided by local GABAergic interneurons (INs) activates ionotropic GABAA and metabotropic GABAB receptors (GABABRs). Despite GABABRs 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 GABABR on their somato-dendritic surface, they fail to produce significant postsynaptic inhibitory currents. Instead, GABABRs selectively inhibit dendritic CaV1.2 (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 GABABRs 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CA1 Region, Hippocampal / cytology
  • CA1 Region, Hippocampal / metabolism*
  • Calcium Channels, L-Type / metabolism*
  • Calcium Signaling / physiology*
  • Dendrites / metabolism
  • GABAergic Neurons / cytology
  • GABAergic Neurons / metabolism
  • Interneurons / cytology
  • Interneurons / metabolism*
  • Long-Term Potentiation / physiology*
  • Male
  • Rats
  • Rats, Inbred WF
  • Receptors, GABA-B / metabolism*
  • Somatostatin / metabolism*
  • Synapses / metabolism

Substances

  • Calcium Channels, L-Type
  • L-type calcium channel alpha(1C)
  • Receptors, GABA-B
  • Somatostatin