Medullary Circuitry Regulating Slow-Wave-Sleep

修改项目摘要/摘要部分 我接受了马萨诸塞州大学医学院神经生物学系助理教授的职位。因此，我申请过渡到R 00阶段，在那里我将继续研究面旁区（PZ）调节睡眠-觉醒周期的电路。最终目标是开发治疗方法，以减少与多种神经系统疾病相关的睡眠中断的功能障碍和负面健康影响。 调节慢波睡眠（SWS）的皮层下结构及其与脑电图（EEG）的关系尚不完全清楚。这种基本知识差距的持续存在是一个重要的问题，因为它降低了我们调节或适当操纵大脑睡眠回路的能力，并阻碍了我们治疗和缓解睡眠中断导致的生理障碍的能力。在K99阶段，正如在K99申请中所提出的，我已经表明，GABA能PZ神经元的选择性激活至少部分地通过抑制臂旁核到基底前脑到皮质的上行唤醒系统来促进自由行为动物的SWS和皮质SWA。R 00阶段的目标与K99申请相同，旨在通过使用新的cre-driver小鼠系和与用于表征PZ GABA能神经元的技术相似的技术，确定其他非GABA能PZ神经元如何有助于SWS和皮质SWA的调节，完成拟定项目。

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.