Circadian desynchronization attenuates information throughput independent of daily rhythms in prefrontal cortex pyramidal neurons

Circadian (daily) rhythms are ubiquitous in biology, from the molecular to behavioral levels. There is growing interest in understanding the functional implications and mechanisms of circadian oscillations in various neural systems, and the consequences of disrupted circadian rhythms on brain function due to our 24/7 modern environment. The prefrontal cortex (PFC) is heavily involved in myriad processes, including working memory, cognition, stress responses, and fear associated behaviors. Many PFC-associated behaviors are time-of-day dependent, yet how time-of-day impacts the fundamental function of neurons in the PFC and potential mechanism(s) by which this occurs remains unknown. Using patch-clamp electrophysiology, we demonstrate that the activity of prelimbic PFC neurons, their synaptic inputs, and action potential dynamics are regulated by time-of-day in a sex specific manner. Further, we show that in males, postsynaptic K+ channels play a central role in mediating these rhythms, suggesting the potential for an intrinsic gating mechanism mediating information throughput. Finally, we demonstrate that environmental circadian desynchronization alters the intrinsic functioning of these neurons and decreases information throughput in part by altering GIRK1/2 channel function. These key discoveries in PFC physiology demonstrate the importance of understanding how daily rhythms contribute to the mechanisms underlying the basic functions of PFC circuitry, and how circadian disruption may impact fundamental properties of neurons.