Mice lacking the transcriptional coactivator PGC-1α exhibit alterations in inhibitory synaptic transmission in the motor cortex

S. E. Dougherty, A. F. Bartley, E. K. Lucas, J. J. Hablitz, L. E. Dobrunz, R. M. Cowell

Research output: Contribution to journalArticle

Abstract

Peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is a transcriptional coactivator known to regulate gene programs in a cell-specific manner in energy-demanding tissues, and its dysfunction has been implicated in numerous neurological and psychiatric disorders. Previous work from the Cowell laboratory indicates that PGC-1α is concentrated in inhibitory interneurons and is required for the expression of the calcium buffer parvalbumin (PV) in the cortex; however, the impact of PGC-1α deficiency on inhibitory neurotransmission in the motor cortex is not known. Here, we show that mice lacking PGC-1α exhibit increased amplitudes and decreased frequency of spontaneous inhibitory postsynaptic currents in layer V pyramidal neurons. Upon repetitive train stimulation at the gamma frequency, decreased GABA release is observed. Furthermore, PV-positive interneurons in PGC-1α -/- mice display reductions in intrinsic excitability and excitatory input without changes in gross interneuron morphology. Taken together, these data show that PGC-1α is required for normal inhibitory neurotransmission and cortical PV-positive interneuron function. Given the pronounced motor dysfunction in PGC-1α -/- mice and the essential role of PV-positive interneurons in maintenance of cortical excitatory:inhibitory balance, it is possible that deficiencies in PGC-1α expression could contribute to cortical hyperexcitability and motor abnormalities in multiple neurological disorders.

Original languageEnglish (US)
Pages (from-to)137-148
Number of pages12
JournalNeuroscience
Volume271
DOIs
StatePublished - Jun 20 2014
Externally publishedYes

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Keywords

  • Inhibitory neurotransmission
  • Interneuron
  • Motor cortex
  • Parvalbumin
  • Peroxisome proliferator-activated receptor gamma coactivator 1α

ASJC Scopus subject areas

  • Neuroscience(all)

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