Nicotine Modulation of Parasympathetic Cardiac Neurons

超出所提供的空间。胎儿尼古丁暴露是婴儿猝死综合症（SIDS）的最高风险因素，尽管有大量的负面宣传，但几乎每四个孕妇中就有一个吸烟。死于小岛屿发展中国家的婴儿有严重的中央介导的心脏减慢。在每个呼吸周期中，心脏通常在吸气时跳得更快，在吸气后跳得更慢，这在很大程度上（如果不是全部的话）是通过呼吸调节副交感神经心脏迷走神经活动来调节的。婴儿死于SIDS被认为是异常的，也许是过度的中枢心肺相互作用，据推测，可能涉及到长时间的吸气后伴随着严重的心率持续下降。然而，令人惊讶的是，尽管在生理和临床上具有重要意义，但对于髓质中介导心脏副交感迷走神经呼吸调节的通路、递质和受体以及这些相互作用如何随着胎儿尼古丁暴露而改变，我们知之甚少。这个项目将直接测试尼古丁受体负责心脏迷走神经细胞呼吸调节的统一假设。我们还将检验胎儿长期暴露于尼古丁会夸大这些心肺反应的假设。为了实现这些目标，我们将利用一种新的脑干准备，使我们能够测量自发的有节奏的呼吸活动和诱发心脏迷走神经神经元的突触反应。我们的初步结果表明，心脏迷走神经神经元在吸气时受到抑制性GABA能和甘氨酸能输入增加的抑制，GABA和甘氨酸能频率的增加是由尼古丁受体的激活介导的。除了激励时的抑制性输入外，我们的初步结果显示心脏迷走神经在激励后通过可能由尼古丁调节的谷氨酸能途径兴奋。这项工作不仅解决了理解新生儿大鼠源于髓质的心肺节律的基础和机制的基本假设，而且还将提示胎儿暴露于尼古丁会改变哪些受体和过程，从而增加小岛屿发展中国家（SIDS）等心肺疾病的风险。网站性能 ======================================== 节结束 ===========================================

EXCEED THE SPACE PROVIDED. 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. PERFORMANCE SITE ========================================Section End===========================================