A role for TrkB.T1 receptors in mammalian sleep and for basal forebrain astrocytes in sleep homeostasis

Sleep remains a poorly understood biological phenomenon. Several important gaps exist in our knowledge regarding the mechanisms that drive homeostatic sleep regulation and the role of glia in this process. To address these gaps, in Chapter 2 we investigated the role of the glia-enriched neurotrophin receptor TrkB.T1 in sleep expression and homeostasis. Constitutive knockout of TrkB.T1 from mice resulted in altered REM sleep time, homeostasis, bout duration, and overall sleep architecture consistent with the sleep disruptions observed in human major depressive disorder (MDD). In Chapter 3, we investigated possible areas of the brain where astrocyte gliotransmission affects sleep homeostasis. Doxycycline infusion into the basal forebrain (BF) of dnSNARE mice suppressed transgene expression and was suggestive of a rescue of wild-type-like sleep homeostasis. These results are consistent with the BF as a key brain region in sleep homeostasis and BF astrocyte gliotransmission as a component of the mechanisms of sleep homeostasis. Overall, these results stimulate additional questions regarding the role of astrocytes in sleep expression and regulation