SYNAPTIC BASIS FOR CENTRAL AUTONOMIC INTEGRATION

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The first order neurons involved in autonomic responses to visceral stimulation are located in the nuclei of the solitary tracts (NTS) and area postrema, a circumventricular organ outside the blood-brain barrier. Integrated autonomic responses to circulating hormones and stress or emotional events are also most likely partially mediated through afferent projections to the NTS. These latter afferents derive respectively (1) from the area postrema, and (2) from forebrain regions such as the prefrontal cortex (PFC) and central nucleus of the amygdala. Pre- and/or postsynaptic interactions between transmitter-specific target and non-target neurons of these afferents are likely to play key roles in modulation of autonomic reflexes. The majority of these interactions have not been established by dual labeling electron microscopic immunocytochemistry. Thus, the goal of proposed Study I is to use these methods to determine in the rat NTS and area postrema whether there is a structural basis for interactions among neurons containing specific transmitters and/or peptides most implicated in autonomic regulation. These include: catecholamines identified by immunoreactivity for the synthesizing enzymes, tyrosine hydroxylase and phenylethanolamine N-methyl transferase; GABA identified by the product or its synthesizing enzyme, glutamic acid decarboxylase; endogenous opiate peptides and neuropeptide Y. The goals of proposed Studies II and III are to determine using tract-tracing and electron microscopic immunocytochemistry (1) whether there is converging afferent input to the NTS from vagal afferents and afferents either from area postrema, PFC or amygdala; and, if so (2) whether these convergences occur on neurons containing one of the putative transmitters identified in Study I. Additionally, in Study II quantitative light microscopic immunocytochemistry and in situ hybridization will be used to determine whether changes in visceral afferents alter the detected levels of neurotransmitter related products or their corresponding mRNA's in the NTS. The findings will further our understanding of the structural and chemical basis for afferent autonomic regulation at the level of the dorsal vagal complex in the rat. More importantly, these studies may provide information relevant to our understanding of the cellular mechanisms underlying autonomic abnormalities in neuropsychiatric illnesses such as schizophrenia as well as in anxiety and panic disorders in human.