GABA-A receptor inhibition of local calcium signaling in spines and dendrites

Joseph J. Marlin, Adam Carter

Research output: Contribution to journalArticle

Abstract

Cortical interneurons activate GABA-A receptors to rapidly control electrical and biochemical signaling at pyramidal neurons. Different populations of interneurons are known to uniquely target the soma and dendrites of pyramidal neurons. However, the ability of these interneurons to inhibit Ca2+ signaling at spines and dendrites is largely unexplored. Here we use whole-cell recordings, two-photon microscopy, GABA uncaging and optogenetics to study dendritic inhibition at layer 5 (L5) pyramidal neurons in slices of mouse PFC. We first showthat GABA-A receptors strongly inhibit action potential (AP)-evoked Ca2+ signals at both spines and dendrites. We find robust inhibition over tens of milliseconds that spreads along the dendritic branch. However, we observe no difference in the amount of inhibition at neighboring spines and dendrites. We then examine the influence of interneurons expressing parvalbumin (PV), somatostatin (SOM), or 5HT3a receptors. We determine that these populations of interneurons make unique contacts onto the apical and basal dendrites of L5 pyramidal neurons. We also show that SOM and 5HT3a but not PV interneurons potently inhibit AP Ca2+ signals via GABA-A receptors at both spines and dendrites. These findings reveal how multiple interneurons regulate local Ca2+ signaling in pyramidal neurons, with implications for cortical function and disease.

Original languageEnglish (US)
Pages (from-to)15898-15911
Number of pages14
JournalJournal of Neuroscience
Volume34
Issue number48
DOIs
Publication statusPublished - Nov 26 2014

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Keywords

  • Calcium signaling
  • Dendrite
  • Inhibition
  • Interneuron
  • Prefrontal cortex
  • Spine

ASJC Scopus subject areas

  • Neuroscience(all)

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