BDNF-TrkB signaling orchestrates the buildup process for local sleep
Much recent scientific work has focused on determining the molecular origins of sleep-wake regulation. Sleep debt accumulates during wakefulness and is accompanied by an increase in slow wave activity (SWA) during sleep, an electroencephalographic (EEG) global marker for sleep need. The use-dependent demands of prior wakefulness increase the intensity of sleep SWA locally. However, the circuitry and molecular identity of this local "sleep pressure" remains unclear. Using pharmacology and optogenetics perturbations, we showed that cortical brain-derived neurotrophic factor (BDNF) regulates the intensity of SWA via the activation of Tyrosine kinase B (TrkB) receptor and cAMP-response element-binding protein (CREB). We identified that the circuitry mediating TrkB-induced sleep SWA involves excitatory pyramidal cells of the cortex's layer 5. We found that increased neuronal firing alone in the somatosensory cortex was not sufficient to increase SWA. Using mathematical modeling of a local network in the brain, we model how BDNF's effects on synaptic strength can increase SWA in ways not achieved through increased firing alone. Together, our findings implicate BDNF-TrkB-CREB signaling pathway in local SWA control during sleep.