The dual function of the basal forebrain parvalbumin neurons in sleep-wake control

Abstract

The basal forebrain (BF) plays a pivotal role in controlling sleep and wakefulness. Recently, the wake-promoting property of GABAergic parvalbumin (PV) neurons in the BF has been shown, and cortical gamma oscillation at ~40Hz are regulated by those neurons. On the other hand, intermittent stimulation at 8Hz of the thalamic reticular nucleus (TRN) increased sleep spindles and NREM sleep. Interestingly, TRN receives robust projections from BF PV neurons; however, their function on sleep-wake control remained unclear. Therefore, we sought to investigate differential roles of BF PV neurons in sleep-wake control. To selectively control BF PV neurons, the double-floxed ChR2-eYFP viral vector was stereotaxically injected into the BF of PV::Cre mice. After two weeks, we recorded sleep-wake profiles at baseline, followed by experimental days with either 40Hz or “spindle-like (intermittent ten light pulses at 8Hz)” stimulation (Kim A, et al., 2012).The durations of wake, NREM and REM sleep in the baseline and stimulation days at the same time of day were compared Spectral analysis of electroencephalogram (EEG) was also performed. Optogenetic stimulation of BF PV neurons at 40Hz at the middle of the light period (ZT06-ZT07) decreased NREM sleep (56.83vs. 66.38% at baseline). On the other hand, intermittent stimulation at 8Hz increase NREM sleep (67.37% vs. 64.16% at baseline). Spectral analyses of EEG showed that delta (0.5-4Hz) and theta (4-7Hz) activity was higher during 40Hz stimulation than baseline but lower during 8Hz stimulation than baseline. This investigation found that intermittent stimulation of BF PV neurons at 8 Hz could increase NREM sleep and subsequently the reduced sleep pressure resulted in decreased delta activity during the stimulation. In contrast to the well-known wake-promoting effect of BF PV stimulation, I propose an additional sleep-promoting role of BF PV neurons contingent upon their firing rates and pattern.