| First Author | Mackenzie-Gray Scott C | Year | 2022 |
| Journal | J Neurophysiol | Volume | 127 |
| Issue | 1 | Pages | 86-98 |
| PubMed ID | 34788174 | Mgi Jnum | J:333088 |
| Mgi Id | MGI:7431014 | Doi | 10.1152/jn.00295.2021 |
| Citation | Mackenzie-Gray Scott C, et al. (2022) PV-specific loss of the transcriptional coactivator PGC-1alpha slows down the evolution of epileptic activity in an acute ictogenic model. J Neurophysiol 127(1):86-98 |
| abstractText | The transcriptional coactivator, PGC-1alpha (peroxisome proliferator-activated receptor gamma coactivator 1alpha), plays a key role in coordinating energy requirement within cells. Its importance is reflected in the growing number of psychiatric and neurological conditions that have been associated with reduced PGC-1alpha levels. In cortical networks, PGC-1alpha is required for the induction of parvalbumin (PV) expression in interneurons, and PGC-1alpha deficiency affects synchronous GABAergic release. It is unknown, however, how this affects cortical excitability. We show here that knocking down PGC-1alpha specifically in the PV-expressing cells (PGC-1alpha(PV-/-)) blocks the activity-dependent regulation of the synaptic proteins, SYT2 and CPLX1. More surprisingly, this cell class-specific knockout of PGC-1alpha appears to have a novel antiepileptic effect, as assayed in brain slices bathed in 0 Mg(2+) media. The rate of occurrence of preictal discharges developed approximately equivalently in wild-type and PGC-1alpha(PV-/-) brain slices, but the intensity of these discharges was lower in PGC-1alpha(PV-/-) slices, as evident from the reduced power in the gamma range and reduced firing rates in both PV interneurons and pyramidal cells during these discharges. Reflecting this reduced intensity in the preictal discharges, the PGC-1alpha(PV-/-) brain slices experienced many more discharges before transitioning into a seizure-like event. Consequently, there was a large increase in the latency to the first seizure-like event in brain slices lacking PGC-1alpha in PV interneurons. We conclude that knocking down PGC-1alpha limits the range of PV interneuron firing and this slows the pathophysiological escalation during ictogenesis.NEW & NOTEWORTHY Parvalbumin expressing interneurons are considered to play an important role in regulating cortical activity. We were surprised, therefore, to find that knocking down the transcriptional coactivator, PGC-1alpha, specifically in this class of interneurons appears to slow ictogenesis. This anti-ictogenic effect is associated with reduced activity in preictal discharges, but with a far longer period of these discharges before the first seizure-like events finally start. Thus, PGC-1alpha knockdown may promote schizophrenia while reducing epileptic tendencies. |
