Mechanisms underlying respiratory motor plasticity

呼吸运动可塑性的机制

• 批准号: 327078-2012
• 负责人: Peever, John
• 金额: $ 2.26万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=571917
• 关键词: Mechanisms; underlying; respiratory; motor; plasticity

Context: The respiratory control system is not just reflexive - it is smart, it learns and in fact it has a working memory. The respiratory system listens to and carefully remembers how previous stimuli affect breathing. Respiratory memory is laid down by adjusting synaptic strength between respiratory neurons. Repeated respiratory stimuli (e.g. apnea) induce a form of memory that strengthens the ability of respiratory motoneurons to trigger contraction of breathing muscles. This type of respiratory motor plasticity is called long-term facilitation (LTF) and it may serve to deepen breathing and improve effective lung ventilation. Rationale: Although the physiological factors that trigger respiratory LTF are known (e.g., apneas), the actual brain circuitry and transmitter pathways that cause LTF remain largely unidentified. This grant will: 1) identify and map-out the neuro-circuits that induce LTF. 2) determine how these circuits communicate with the respiratory system to elicit LTF of breathing. Research Approach and Aims: Work from my previous NSERC Discovery Grant identified a novel type of respiratory LTF that is caused by repeated apneas (Tadjalli et al, J. Neuroscience, 30(50):16886-95, 2010). In anesthetized and spontaneously breathing rats, we found that repeated airway occlusions - similar to those in obstructive sleep apnea - caused LTF of respiratory activity in upper airway muscles, e.g., genioglossus. The physiological factor responsible for apnea-induced LTF activation was the lung afferent feedback caused by repeated airway obstructions. Importantly, activation of the noradrenergic system was required to elicit LTF. How this transmitter system initiates LTF is unknown. This grant proposal is a direct extension of our previous work. Its overall aim is to identify and define the noradrenergic mechanisms and pathways responsible for respiratory LTF.

背景：呼吸控制系统不仅仅是反射性的-它很聪明，它会学习，事实上它有工作记忆。呼吸系统倾听并仔细记住先前的刺激如何影响呼吸。呼吸记忆是通过调节呼吸神经元之间的突触强度来形成的。重复的呼吸刺激（例如呼吸暂停）诱导一种形式的记忆，增强呼吸运动神经元触发呼吸肌收缩的能力。这种类型的呼吸运动可塑性被称为长期促进（LTF），它可能有助于加深呼吸和改善有效的肺通气。 理由：虽然触发呼吸LTF的生理因素是已知的（例如，呼吸暂停），导致LTF的实际脑回路和递质通路在很大程度上仍未被确定。这项资助将：1）识别和绘制出诱导LTF的神经回路。 2)确定这些回路如何与呼吸系统通信以引起呼吸的LTF。 研究方法和目的：来自我之前的NSERC发现资助的工作鉴定了由反复呼吸暂停引起的新型呼吸LTF（Tadjalli等人，J. Neuroscience，30（50）：16886-95，2010）。 在麻醉和自主呼吸的大鼠中，我们发现反复的气道阻塞-类似于阻塞性睡眠呼吸暂停-导致上气道肌肉呼吸活动的LTF，例如，颏舌肌呼吸暂停引起LTF激活的生理因素是反复气道阻塞引起的肺传入反馈。重要的是，去甲肾上腺素能系统的激活需要引起LTF。发射机系统如何启动LTF尚不清楚。 这项资助计划是我们以前工作的直接延伸。其总体目标是确定和定义负责呼吸LTF的去甲肾上腺素能机制和途径。