One important question concerns how PGC-1α expression is down-regulated in the cortex of KO mice following social isolation. Accumulating evidence suggests that neural expression of PGC-1α is activity-dependent and requires intracellular calcium influx. For example, depolarization of neurons by NMDAR activation or high-potassium solution increases PGC-1α expression (33), and NMDA antagonists or calcium channel blockade prevent such increases (34,35). Conversely, blockade of neuronal activity by tetrodotoxin or sensory deprivation decreases PGC-1α expression in the visual cortex (36). In the present study, it is possible that protracted maturation of the NMDAR-deleted PV neurons (Zsiros V., PhD, unpublished, 2012) might impair the activity-dependent expression of PGC-1α after social isolation. Additional studies are necessary to delineate the mechanisms involved.
