Molecular and cellular rhythms in excitatory and inhibitory neurons in the mouse prefrontal cortex.

Abstract

While previous studies have found rhythms in gene expression in the prefrontal cortex (PFC), the contribution of different cell types and potential variation by sex has not been determined. Of interest are excitatory pyramidal cells and inhibitory parvalbumin (PV) interneurons, as the interaction between these cells is thought to underlie gamma oscillations and play a role in schizophrenia. We identify cell-type-specific rhythms in ribosome-associated transcripts from PV and pyramidal cells in the mouse PFC and assess rhythms in PV cell electrophysiology. We find that while core molecular clock genes are synchronized between cell types, pyramidal cells have nearly twice as many rhythmic transcripts as PV cells (35% vs. 18%). Moreover, in contrast to PV cells, rhythmic transcripts in pyramidal cells show substantial overlap between sexes. Additionally, there is a sex-specific reduction in action potential amplitude and spike frequency adaptation during the dark phase in PV cells from females. This study demonstrates that rhythms in gene expression and electrophysiological properties in the PFC vary by cell type and by sex. Moreover, the biological processes associated with rhythmic transcripts may provide insight into the unique functions of rhythms in these cells, as well as their selective vulnerabilities to circadian disruption.