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

表征吸气后行为的神经回路及其与呼吸的协调

• 批准号: 10315099
• 负责人: Alyssa Huff
• 金额: $ 6.64万
• 依托单位: SEATTLE CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-18 至 2025-02-17
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10315099
• 关键词: Characterizing; neural; circuitry; postinspiratory; behaviors

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.

项目摘要 呼吸与吸气后行为（如吞咽和喉内收）的协调， 对健康至关重要。在吸气后和吞咽过程中，喉活动失调发生在许多 神经和呼吸相关疾病，如阻塞性睡眠呼吸暂停，并可增加 吞咽障碍（吞咽困难）和误吸。吞咽困难是这些疾病患者的主要问题， 并且目前没有治疗或预防吞咽困难的方法。这一赤字部分是由于缺乏 呼吸与吸气后喉功能及吞咽功能协调性的研究。最近 描述脑干吸气后复合体（皮科）被认为控制吸气后，但它在其他 喉部行为尚未被研究。我们测试了一个全新的假设，即兴奋性延髓 从皮科到吞咽模式发生器的传输在吞咽相关的吸气后 行为我们的目标是确定皮科在吸气后喉活动和吞咽中的作用， 调查背侧吞咽组（DSG）和腹侧呼吸组之间的潜在协调 （VRG）。基于初步数据，我们假设皮科是吸气后活动和 吞咽，并与孤束核中假定的吞咽模式发生器有关 （nTS）。我们相信皮科在与吞咽相关的节奏活动中发挥着作用，其中包括nTS作为 推测的吞咽节律发生器，其投射至腹侧呼吸中枢。我们在体内使用两个 制备：麻醉和警觉的小鼠结合电生理学、新型光遗传学和 神经像素记录来检验这些假设。我们预测皮科活动与呼吸的神经协调 而非呼吸中枢在麻醉和未麻醉制剂之间是相似的。调查 警觉动物的皮科对于表征吞咽和喉部的自然行为是重要的 吸气后活动的翻译方式。