The central parasympathetic control of cardiac rate, atrio-ventricular conduction,and myocardial contractility is mediated by inhibitory efferent axons within the vagus nerve. These parasympathetic preganglionic axons originate in the medulla within neurons of the nucleus ambiguus(NA). Physiological evidence suggests that four anatomically segregated parasympathetic cardiac ganglia selectively project to the sinoatrial (SA) node, Atrioventricular(AV) node, and atrial or ventricular smooth muscle to regulate SA automaticity, AV conduction,atrial contractility and ventricular contractility, respectively. Recent anatomical and physiological evidence from our laboratory strongly support the hypothesis that anatomically separated and functionally selective NA neurons independently control SA rate and AV conduction. Data indicate that there is a longitudinal cardiotopic organization of negative chronotropic and negative dromotropic neurons in the caudal NA and rostral NA, respectively. This CNS organization mirrors the organization of functionally selective cardiac components of the peripheral vagus nerve. Other data support the hypothesis that functionally different populations of NA cardiomotor neurons are controlled by CNS afferent nerve terminals utilizing different neurotransmitters or receptors. The experiments proposed are therefore designed to answer the question, """""""" How are functionally selective central and peripheral cardioinhibitory vagal motor neurons organized and controlled?"""""""" Dual labeling light- and electron microscopic histochemical and immunocytochemical techniques will be used. The investigators propose to 1) use two different independent light microscopic neuroanatomical tracing methods to further test the hypothesis that anatomically separated and functionally selective NA neurons independently control SA rate and AV conduction; 2) define by light microscopy the cardiotopic organization of NA neurons which are functionally associated with the control of atrial and ventricular contractility; 3) define by double labeling electron microscopy, the synaptic interactions of afferent nerve terminals containing the neurotransmitters substance P, serotonin, neuropeptide Y, and enkephalin with negative chronotropic, negative dromotropic and presumptive negative inotropic NA neurons; and 4) determine the ultrastructural relationships between selected cardiorespiratory divisions of the nucleus of the solitary tract (NTS) and negative chronotropic or negative dromotropic NA neurons. This information will help define the neuronal circuitry mediating the solitario-vagal components of the baro- and chemoreceptor reflexes. The experiments which are proposed can potentially enhance our ability to define the neuronal circuitry underlying parasympathetic regulation of the heart.
Showing the most recent 10 out of 12 publications
