Medullary Circuitry Regulating Slow-Wave-Sleep

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Modified Project Summary/Abstract Section I have received and accepted a position as an Assistant Professor in the Department of Neurobiology, University of Massachusetts Medical School. Therefore, I am applying for the transition to the R00 phase where I will continue to investigate parafacial zone (PZ) circuitry regulating sleep-wake cycle. The ultimate goal is to develop treatments to reduce the dysfunction and negative health effects of sleep disruption associated with multiple neurologic disorders. The subcortical structures regulating slow-wave sleep (SWS) and its electroencephalogram (EEG) correlate are incompletely understood. Continued existence of this fundamental knowledge gap represents an important problem because it reduced our ability to modulate or appropriately manipulate the brain’s sleep circuitry and hampers our ability to treat and alleviate the physiological disorders that result from sleep disruption. During the K99 phase, and as proposed in the K99 application, I have shown that selective activation of GABAergic PZ neurons promotes SWS and cortical SWA in freely behaving animals at least in part by inhibiting the parabrachial nucleus to basal forebrain to cortex ascending arousal system. The objective of the R00 phase remains identical to the K99 application and aims to finish the proposed projects by determining how other non-GABAergic PZ neurons might contribute to the regulation of SWS and cortical SWA, using a new cre-driver mouse line and similar techniques to those employed to characterize PZ GABAergic neurons.