Mechanism of Cardiorespiratory Rhythm in Neonates

描述：（由申请人提供）心血管的神经控制 和呼吸系统是高度相关的。在每个呼吸周期中， 心脏在吸气时跳动得更快，在吸气后跳动得更慢， 这被称为呼吸性窦性心律不齐。这个心肺功能 相互作用发生在中枢神经系统内并且主要是介导的， 如果不是全部的话，通过心脏的副交感神经支配。呼吸 窦性心律不齐在许多疾病状态中减少， 推测可能与心肺控制异常有关， 婴儿猝死综合症（SIDS）。这一建议是一个合乎逻辑的延伸， 上一个供资期间取得的成果，并将建立一个 统一的框架，确定神经元和机制负责 心脏副交感迷走神经活动的呼吸调节。我们将使用一个 一种新的体外制剂， 引起绿色荧光表达创新的跨突触病毒 一种识别投射到心脏迷走神经元的神经元的蛋白质（GFP） 而不改变它们的电生理特性。具体地说， 我们将测试心脏迷走神经元是否在吸气时受到抑制， 抑制性GABA能输入的频率增加， GABA频率由突触前烟碱受体的激活介导。我们 还将检验心脏迷走神经元直接兴奋的假设， 在吸气后通过电突触，可以取消间隙 连接阻断剂。此外，我们将识别和描述节奏 神经元的呼吸活动，突触，并使间隙连接 与心脏迷走神经元接触。这项工作不仅将解决 基本假设理解的基础和机制 新生大鼠起源于髓质的心肺节律， 还将提示哪些受体和过程可能会被改变， 心肺系统疾病，如SIDS。

DESCRIPTION: (Provided By Applicant) The neural control of the cardiovascular and respiratory systems is highly interrelated. During each respiratory cycle, the heart beats more rapidly in inspiration and slows during post-inspiration, which is referred to as respiratory sinus arrhythmia. This cardio-respiratory interaction occurs within the central nervous system and is mediated largely, if not entirely, via the parasympathetic innervation of the heart. Respiratory sinus arrhythmia is diminished in many disease states and it has been speculated that an abnormality of cardio-respiratory control may be involved in sudden infant death syndrome (SIDS). This proposal is a logical extension of the results obtained during the previous funding period and will build a unifying framework that identifies the neurons and mechanisms responsible for respiratory modulation of cardiac parasympathetic vagal activity. We will use a novel in-vitro preparation that maintains rhythmic respiratory activity with an innovative transsynaptic virus that evokes expression of green fluorescent protein (GFP) that identifies neurons that project to cardiac vagal neurons in-vitro without altering their electrophysiological properties. Specifically, we will test whether cardiac vagal neurons are inhibited during inspiration by an increased frequency of inhibitory GABAergic inputs, and that the increased GABA frequency is mediated by activation of presynaptic nicotinic receptors. We will also test the hypothesis that cardiac vagal neurons are directly excited during post-inspiration via electrical synapses which can be abolished by gap junction blockers. Furthermore, we will identify and characterize the rhythmic respiratory activity of the neurons that synapse upon, and make gap junction contacts with, cardiac vagal neurons. This work will not only address hypotheses fundamental to understanding the basis and mechanisms of cardiorespiratory rhythms in the neonatal rat that originate in the medulla, but will also suggest which receptors and processes could be altered in diseases of the cardiorespiratory system such as SIDS.