Genetic Activation, Inactivation, and Deletion Reveal a Limited And Nuanced Role for Somatostatin-Containing Basal Forebrain Neurons in Behavioral State Control.

Recent studies have identified an especially important role for basal forebrain GABAergic (BF^VGAT) neurons in the regulation of behavioral waking and fast cortical rhythms associated with cognition. However, BF^VGAT neurons comprise several neurochemically and anatomically distinct subpopulations, including parvalbumin-containing BF^VGAT neurons and somatostatin-containing BF^VGAT neurons (BF^SOM neurons), and it was recently reported that optogenetic activation of BF^SOM neurons increases the probability of a wakefulness to non-rapid-eye movement (NREM) sleep transition when stimulated during the rest period of the animal. This finding was unexpected given that most BF^SOM neurons are not NREM sleep active and that central administration of the synthetic somatostatin analog, octreotide, suppresses NREM sleep or increases REM sleep. Here we used a combination of genetically driven chemogenetic and optogenetic activation, chemogenetic inhibition, and ablation approaches to further explore the in vivo role of BF^SOM neurons in arousal control. Our findings indicate that acute activation or inhibition of BF^SOM neurons is neither wakefulness norNREMsleep promoting and is without significant effect on the EEG, and that chronic loss of these neurons is without effect on total 24 h sleep amounts, although a small but significant increase in waking was observed in the lesioned mice during the early active period. Our in vitro cell recordings further reveal electrophysiological heterogeneity in BF^SOM neurons, specifically suggesting at least two distinct subpopulations. Together, our data support the more nuanced view that BF^SOM neurons are electrically heterogeneous and are not NREM sleep or wake promoting per se, but may exert, in particular during the early active period, a modest inhibitory influence on arousal circuitry. [ABSTRACT FROM AUTHOR]