Characterizing the neural circuitry of postinspiratory behaviors and its coordination with breathing

项目总结 呼吸与吸气后行为的协调，如吞咽和喉部内收 对健康是必不可少的。许多患者在吸气和吞咽后喉部活动失调 神经和呼吸相关疾病，如阻塞性睡眠呼吸暂停，并可增加患上 吞咽障碍(吞咽困难)和吞咽障碍。吞咽困难是这些疾病患者的主要问题， 而且目前还没有治愈或预防吞咽困难的治疗方法。造成这种赤字的部分原因是缺乏 吸气吞咽后呼吸与喉功能协调性的研究。最近的 已描述的脑干吸气后复合体(Pico)被认为控制后吸气，但它在其他 喉部行为还没有被研究过。我们测试了一个全新的假设，即兴奋性延髓 从Pico到吞咽模式产生器的传递在吞咽相关的吸气后状态中起作用 行为。我们的目标是确定Pico在吸气后喉部活动和吞咽中的作用，以及 研究背部吞咽组(DSG)和腹侧呼吸组之间的潜在协调 (VRG)。根据初步数据，我们假设Pico是吸气后活动和呼吸的中枢 吞咽，并与孤束核中推测的吞咽模式生成器有联系 (新界别)。我们认为Pico在燕子相关的节律活动中发挥了作用，其中包括NTS 推测为吞咽节律发生器，投射到腹侧呼吸中枢。我们在体内使用了两个 准备：麻醉清醒小鼠结合电生理学、新型光遗传学和 神经像素记录来验证这些假说。我们预测Pico活动与呼吸的神经协调 麻醉和未麻醉制剂之间的非呼吸中枢是相似的。调查 警觉动物的Pico对于描述燕子和喉咙的自然行为很重要 以平移的方式进行吸气后活动。

PROJECT SUMMARY Coordination of breathing with postinspiratory behaviors such as swallowing and laryngeal adduction is essential to health. Dysregulation of laryngeal activity during postinspiration and swallow occurs in many neurological and breathing-related disorders, such as obstructive sleep apnea, and can increase the risk of disordered swallow (dysphagia) and aspiration. Dysphagia is a major problem in patients with these diseases, and there are currently no treatments to cure or prevent dysphagia. This deficit is due in part to the lack of studies on coordination of breathing with laryngeal function of postinspiration and swallow. The recently described brainstem Postinspiratory Complex (PiCo) is thought to control postinspiration, yet its role in other laryngeal behaviors has not been studied. We test a fundamentally new hypothesis that excitatory medullary transmission from PiCo to the swallow pattern generator plays a role in swallow-related postinspiratory behavior. Our goals is to define the role of PiCo in postinspiratory laryngeal activity and swallow, and investigate potential coordination between the dorsal swallow group (DSG) and the ventral respiratory group (VRG). Based on preliminary data, we hypothesize that PiCo is a hub for both postinspiratory activity and swallowing, and has connections to the presumed swallow pattern generator in the nucleus tractus solitarius (nTS). We believe PiCo plays a role in swallow-related rhythmic activities which includes the nTS as the presumed swallow rhythm generator with projections to ventral respiratory centers. We use two in-vivo preparation: anesthetized and alert mouse combined with electrophysiology, novel optogenetics and Neuropixel recordings to test these hypotheses. We predict neural coordination of PiCo activity with respiratory and non-respiratory centers is similar between anesthetized and unanesthetized preparations. Investigating PiCo in an alert animal is important for characterizing the natural behaviors of swallow and laryngeal postinspiratory activity in a translational manner.