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。死于SIDS的婴儿被认为有不正常的，也许是夸张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持续呼吸

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.