MECHANISM OF CARDIORESPIRATORY RHYTHM IN NEONATES

神经控制心血管和呼吸系统

The neural control of the cardiovascular and respiratory systems are highly interrelated. For example, in each respiratory cycle the heart beats more rapidly in inspiration and slows during post-inspiration and expiration (often referred to as respiratory sinus arrhythmia). As another example, stimulation of sensory laryngeal receptors evokes a period of apnea and maintained a dramatic decrease in heart rate. This laryngeal reflex can be so exaggerated in newborns in can lead to death in neonatal animals, and has been suggested as a possible cause for sudden infant death syndrome (SIDS). This cardio-respiratory interactions occur within the central nervous system and are mediated largely, if not entirely, via the vagal innervation of the heart. Surprisingly, however, despite the physiological and clinical importance of cardiac vagal activity, little is known about its initiation and control within the central nervous system in neonates or adults, and no pathway from identified respiratory to cardiac vagal neurons within the medulla has yet been identified. This project will directly test the hypothesis that superior laryngeal motor-neurons excite vagal cardioinhibitory neurons via a direct monosynaptic pathway, and, in addition, act presynaptically to enhance other synapses impinging on cardiac vagal neurons. Superior laryngeal neurons are likely mediators of cardio-respiratory interaction because these neurons are active in post-inspiration, co-localized with cardiac vagal neurons, and have many axon collaterals within the nucleus ambiguus. To test this hypothesis, techniques that are quite new to this field, such as fluorescent retrograde identification of cardiac vagal and superior laryngeal motor-neurons, and dual patch clamp electrophysiological techniques will be used. This work will not only address issues and mechanisms fundamental to understanding the basis of cardio-respiratory rhythms in the neonatal medulla, but will also suggest which receptors and processes could be altered in diseases of the cardio-respiratory system such as SIDS.