Nicotine Modulation of Parasympathetic Cardiac Neurons

超出所提供的空间。胎儿接触尼古丁是婴儿猝死综合症（SIDS）的最高风险因素，尽管有大量的负面宣传，但几乎每四名孕妇中就有一名吸烟。死于SIDS的婴儿有严重的中枢介导的心脏减慢。在每个呼吸周期期间，心脏通常在吸气时跳动得更快，而在吸气后减慢，这如果不是完全的话，也主要是通过副交感神经心脏迷走神经活动的呼吸调节来介导的。死于SIDS的婴儿被认为具有异常的并且可能是夸大的中枢心肺相互作用，并且已经推测可能涉及长时间的吸气后伴随着心率的严重持续降低。然而，令人惊讶的是，尽管生理和临床上的重要性，很少有人知道的途径，递质和受体介导的呼吸调制的副交感神经心脏迷走神经元在髓质和这些相互作用可能会改变胎儿尼古丁暴露。这个项目将直接测试尼古丁受体负责心脏迷走神经元呼吸调节的统一假设。我们还将检验长期胎儿尼古丁暴露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节律呼吸活动和诱发的心脏迷走神经元的突触反应。我们的初步研究结果表明，心脏迷走神经元在吸气过程中被抑制性GABA能和甘氨酸能输入增加，GABA和甘氨酸能频率的增加是由烟碱受体的激活介导的。除了在吸气过程中的抑制性输入，我们的初步研究结果表明，心脏迷走神经元兴奋在吸气后的一个amatergic途径，这可能是由尼古丁调制。这项工作不仅将解决基本的假设，以了解起源于髓质的新生大鼠心肺节律的基础和机制，但也将表明哪些受体和过程可能会改变胎儿暴露于尼古丁，增加心肺疾病的风险，如婴儿猝死综合征。性能现场=

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===========================================