Mechanism of Cardiorespiratory Rhythm in Neonates

描述（由申请人提供）：潜水反射是最强大的自主反射。潜水反射的刺激引起明显的心动过缓，单次面部潜水时心率下降高达51%。潜水反射是非常有益的，防止水侵入肺部，引起心动过缓，减少心肌耗氧量。然而，过度的跳水反射与婴儿猝死综合征（SIDS）有关。尽管潜水反射的强度和临床重要性，几乎所有以前的神经生物学研究都是解剖的而不是功能的。本研究的长期目标是为脑干潜水反射的神经生物学和受体提供一个全面的功能蓝图。为了实现这些目标，我们将利用一种新的脑干准备方法，使我们能够刺激三叉神经感觉传入纤维，同时表征自发节律性呼吸活动和心脏迷走神经中诱发的突触反应。具体来说，我们将测试三叉神经感觉传入纤维的刺激引起中枢呼吸暂停并招募到副交感神经心脏迷走神经的兴奋通路的假设。这条通路的电生理特性将被表征，参与的受体将被识别，突触在这条脑干通路中的位置将被绘制。我们还将确定吸气诱发的gaba能和甘氨酸能神经传递到心脏迷走神经是否会被潜水反射抑制，并确定负责的神经递质。最近的研究表明，脑干中的5-羟色胺能神经元和5-羟色胺（5-羟色胺，5-HT）受体在中枢呼吸功能中起重要作用，脑干5-HT功能异常也与SIDS密切相关。然而，5-羟色胺受体改变脑干心肺相互作用并增加小岛屿发展中国家风险的机制尚不清楚。在AIM 3中，我们将检验潜水反射的脑干通路由不同的5-羟色胺受体内源性和差异调节的假设。

DESCRIPTION (provided by applicant): The diving reflex is the most powerful autonomic reflex. Stimulation of the diving reflex evokes a pronounced bradycardia with heart rate decreasing up to 51% upon a single facial submersion. The diving reflex is highly beneficial by preventing invasion of water into the lungs and evoking a bradycardia that reduces myocardial oxygen consumption. However an exaggerated diving reflex has been implicated in sudden infant death syndrome (SIDS). Despite the strength and clinical importance of the diving reflex nearly all previous neurobiological studies have been anatomical rather than functional. The long-term goal of the present proposal is to provide a comprehensive functional blueprint of the neurobiology and receptors that mediate the diving reflex in the brainstem. To accomplish these goals we will utilize a novel brainstem preparation that allows us to stimulate trigeminal sensory afferent fibers and simultaneously characterize spontaneous rhythmic respiratory activity and evoked synaptic responses in cardiac vagal neurons. Specifically we will test the hypothesis that stimulation of trigeminal sensory afferent fibers evokes a central apnea and recruits an excitatory pathway to parasympathetic cardiac vagal neurons. The electrophysiological properties of this pathway will be characterized, receptors involved will be identified, and the location of the synapses within this brainstem pathway will be mapped. We will also determine whether inspiratory evoked GABAergic and glycinergic neurotransmission to cardiac vagal neurons is inhibited by evoking the dive reflex, and identify the neurotransmitters responsible. Recent work has shown serotonergic neurons and serotonin (5-hydroxytryptamine, 5-HT) receptors in the brainstem play an essential role in central respiratory function and abnormalities in brainstem 5-HT function are also strongly associated with SIDS. However the mechanisms by which 5-HT receptors alter cardiorespiratory interactions in the brainstem and increase the risk of SIDS is unknown. In AIM 3 we will test the hypothesis that the brainstem pathways of the dive reflex are endogenously and differentially modulated by different 5-HT receptors.