Nicotine Modulation of Parasympathetic Cardiac Neurons

胎儿尼古丁暴露是婴儿猝死综合症（SIDS）的最高风险因素，尽管如此， 近四分之一的孕妇吸烟。的婴儿 死于SIDS的人有严重的中枢介导的心脏减慢。在每个呼吸周期中， 心脏通常在吸气时跳动得更快，而在吸气后减慢，这在很大程度上是介导的， 如果不是全部的话，通过对副交感神经心脏迷走神经活动的呼吸调节。婴儿屈服于 SIDS被认为有异常的，可能是夸大的中枢心肺相互作用， 据推测，长时间的吸气后伴随着严重的维持性 心率下降可能与此有关然而，令人惊讶的是，尽管生理和临床 重要性很少有人知道的途径，递质和受体，介导的呼吸 延髓中的副交感心脏迷走神经元的调节以及这些相互作用如何改变 与胎儿尼古丁接触有关 这个项目将直接测试尼古丁受体负责的统一假设， 心脏迷走神经元的呼吸调节。我们还将检验慢性胎儿尼古丁 暴露会夸大这些心肺反应。为了实现这些目标，我们将利用一本小说。 脑干准备，使我们能够测量自发节律呼吸活动和诱发 心脏迷走神经元的突触反应。我们的初步结果表明，心脏迷走神经元是 在吸气期间通过增加抑制性GABA能和甘氨酸能输入而抑制， 在GABA和甘氨酸能频率是由烟碱受体的激活介导的。除了有 我们的初步结果表明，心脏迷走神经元兴奋， 吸入后通过尼古丁能途径，这可能是由尼古丁调节。这项工作不仅将 解决基本的假设，以了解基础和机制的心肺节律 在新生大鼠中，起源于髓质，但也将提示哪些受体和过程可以 胎儿暴露于尼古丁会改变其呼吸系统功能，从而增加患SIDS等心肺疾病的风险。

Fetal nicotine exposure is the highest risk factor for Sudden Infant Death Syndrome (SIDS) and yet despite substantial adverse publicity nearly one out of every four pregnant women smoke tobacco. Infants that succumb to SIDS have a severe centrally mediated slowing of the heart. During each respiratory cycle the heart normally beats more rapidly in inspiration and slows during post-inspiration, which is mediated largely, if not entirely, via respiratory modulation of parasympathetic cardiac vagal activity. Infants that succumb to SIDS are thought to have abnormal and perhaps exaggerated central cardiorespiratory interactions, and it has been speculated that a prolonged period of post-inspiration accompanied by a severe maintained decrease in heart rate, may be involved. Surprisingly, however, despite the physiological and clinical importance little is known about the pathways, transmitters and receptors that mediate respiratory modulation of parasympathetic cardiac vagal neurons in the medulla and how these interactions may change with fetal nicotine exposure. This project will directly test the unifying hypothesis that nicotinic receptors are responsible for the respiratory modulation of cardiac vagal neurons. We will also test the hypothesis that chronic fetal nicotine exposure exaggerates these cardiorespiratory responses. To accomplish these aims we will utilize a novel brainstem preparation that allows us to measure spontaneous rhythmic respiratory activity and evoked synaptic responses in cardiac vagal neurons. Our preliminary results show cardiac vagal neurons are inhibited during inspiration by increased inhibitory GABAergic and glycinergic inputs, and that the increases in GABA and glycinergic frequencies are mediated by activation of nicotinic receptors. In addition to the inhibitory inputs during inspiration, our preliminary results show cardiac vagal neurons are excited during post-inspiration by a glutamatergic pathway which may be modulated by nicotine. 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 by fetal exposure to nicotine which increases the risk of cardiorespiratory diseases such as SIDS.