| First Author | Dougherty SE | Year | 2014 |
| Journal | Neuroscience | Volume | 271 |
| Pages | 137-48 | PubMed ID | 24769433 |
| Mgi Jnum | J:210606 | Mgi Id | MGI:5571520 |
| Doi | 10.1016/j.neuroscience.2014.04.023 | Citation | Dougherty SE, et al. (2014) Mice lacking the transcriptional coactivator PGC-1alpha exhibit alterations in inhibitory synaptic transmission in the motor cortex. Neuroscience 271:137-48 |
| abstractText | Peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha) 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-1alpha 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-1alpha deficiency on inhibitory neurotransmission in the motor cortex is not known. Here, we show that mice lacking PGC-1alpha 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-1alpha -/- mice display reductions in intrinsic excitability and excitatory input without changes in gross interneuron morphology. Taken together, these data show that PGC-1alpha is required for normal inhibitory neurotransmission and cortical PV-positive interneuron function. Given the pronounced motor dysfunction in PGC-1alpha -/- mice and the essential role of PV-positive interneurons in maintenance of cortical excitatory:inhibitory balance, it is possible that deficiencies in PGC-1alpha expression could contribute to cortical hyperexcitability and motor abnormalities in multiple neurological disorders. |
