Major Differences in Inhibitory Synaptic Transmission onto Two Neocortical Interneuron Subclasses

Alberto Bacci, Uwe Rudolph, John R. Huguenard, David A. Prince

Research output: Contribution to journalArticlepeer-review

Abstract

Locally projecting GABAergic interneurons are the major providers of inhibition in the neocortex and play a crucial role in several brain functions. Neocortical interneurons are connected via electrical and chemical synapses that may be crucial in modulating complex network oscillations. We investigated the properties of spontaneous and evoked IPSCs in two morphologically and physiologically identified interneuron subtypes, the fast-spiking (FS) and low threshold-spiking (LTS) cells in layer V of rodent sensorimotor cortex. We found that IPSCs recorded in FS cells were several orders of magnitude more frequent, larger in amplitude, and had faster kinetics than IPSCs recorded in LTS cells. GABAA receptor α- and β-subunit selective modulators, zolpidem and loreclezole, had different effects on IPSCs in FS and LTS interneurons, suggesting differential expression of GABAA receptor subunit subtypes. These pharmacological data indicated that the α1 subunit subtype is poorly expressed by LTS cells but makes a large contribution to GABAA receptors on FS cells. This was confirmed by experiments performed in genetically modified mice in which the α1 subunit had been made insensitive to benzodiazepine-like agonists. These results suggest that differences in IPSC waveform are likely attributable to distinctive expression of GABAA receptor subunits in FS and LTS cells. The particular properties of GABAergic input on different interneuronal subtypes might have important consequences for generation and pacing of cortical rhythms underlying several brain functions. Moreover, selective pharmacological manipulation of distinct inhibitory circuits might allow regulation of pyramidal cell activities under specific physiological and pathophysiological conditions.

Original languageEnglish (US)
Pages (from-to)9664-9674
Number of pages11
JournalJournal of Neuroscience
Volume23
Issue number29
DOIs
StatePublished - Oct 22 2003
Externally publishedYes

Keywords

  • GABA
  • GABA receptors
  • Inhibition
  • Interneurons
  • Neocortex
  • Synaptic transmission

ASJC Scopus subject areas

  • Neuroscience(all)

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