2014 journal article
Mice lacking the transcriptional coactivator PGC-1α exhibit alterations in inhibitory synaptic transmission in the motor cortex
Neuroscience, 271, 137–148.
author keywords: peroxisome proliferator-activated receptor gamma coactivator 1 alpha; parvalbumin; inhibitory neurotransmission; motor cortex; interneuron
MeSH headings : Action Potentials / physiology; Animals; Electric Stimulation; Green Fluorescent Proteins / genetics; Green Fluorescent Proteins / metabolism; Inhibitory Postsynaptic Potentials / physiology; Interneurons / pathology; Interneurons / physiology; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Motor Cortex / pathology; Motor Cortex / physiology; Neural Inhibition / physiology; Neurons / pathology; Neurons / physiology; Parvalbumins / metabolism; Patch-Clamp Techniques; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Pyramidal Cells / pathology; Pyramidal Cells / physiology; Synaptic Transmission / physiology; Tissue Culture Techniques; Transcription Factors / deficiency; Transcription Factors / genetics; Transcription Factors / metabolism; gamma-Aminobutyric Acid / metabolism
TL;DR:
It is shown that mice lacking PGC-1α exhibit increased amplitudes and decreased frequency of spontaneous inhibitory postsynaptic currents in layer V pyramidal neurons, and the essential role of PV-positive interneurons in maintenance of cortical excitatory:inhibitory balance is maintained.
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Source: Crossref
Added: July 27, 2019
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.
