The neural control of the cardiovascular and respiratory systems is highly interrelated. During each respiratory cycle, the heart beats more rapidly in inspiration and slows during post-inspiration, which is referred to as respiratory sinus arrhythmia. This cardio-respiratory interaction occurs within the central nervous system and is mediated largely, if not entirely, via the parasympathetic innervation of the heart. Respiratory sinus arrhythmia is diminished in many disease states and it has been speculated that an abnormality of cardio-respiratory control may be involved in sudden infant death syndrome (SIDS). This proposal is a logical extension of the results obtained during the previous funding period and will build a unifying framework that identifies the neurons and mechanisms responsible for respiratory modulation of cardiac parasympathetic vagal activity. We will use a novel in-vitro preparation that maintains rhythmic respiratory activity with an innovative transsynaptic virus that evokes expression of green fluorescent protein (GFP) that identifies neurons that project to cardiac vagal neurons in-vitro without altering their electrophysiological properties. Specifically, we will test whether cardiac vagal neurons are inhibited during inspiration by an increased frequency of inhibitory GABAergic inputs, and that the increased GABA frequency is mediated by activation of presynaptic nicotinic receptors. We will also test the hypothesis that cardiac vagal neurons are directly excited during post-inspiration via electrical synapses which can be abolished by gap junction blockers. Furthermore, we will identify and characterize the rhythmic respiratory activity of the neurons that synapse upon, and make gap junction contacts with, cardiac vagal neurons. 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 in diseases of the cardiorespiratory system such as SIDS.
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