This is an anatomical project to study the organization of visceral pathways to the forebrain. These pathways are hypothesized to mediate viscerally induced changes in emotion, cortical arousal, and behavior. The specific hypothesis to be tested is that visceral and especially cardiopulmonary stimuli, reach the cerebral cortex through projections from the nucleus of the solitary (NTS) tract to midline-intralaminar thalamic nuclei (MIT), where they may be widely distributed to cortex and basal ganglia. Study I will use anterograde and retrograde tracers to determine: a) whether there is a direct MIT connection from cardiopulmonary afferents; b) if so, whether the projection arises from specific subnuclei within the NTS; c) if the MIT inputs are topographically organized; d) if the NTS-MIT connection is characterized by a particular transmitter phenotype; e) if, using electron microscopy, the NTS-MIT projection neurons are directly innervated by primary vagal fibers. Other studies will determine the extent to which the indirect NTS pathway from the rostral ventrolateral medulla (RVL) is connected with MIT, focusing on known functional subdivisions of the RVL. Study II will determine the cortical and basal ganglia targets of visceroreceptive MIT projection neurons. Study III will establish the extent to which the visceral projections to the MIT are collateralized to provide parallel processing to other areas known to process emotional and autonomic information, such as the RVL, intermediolateral cell column, paraventricular nucleus of the hypothalamus, and amygdala. Study IV will examine, by measuring expression of c-fos and c-jun, whether RVL or vagal stimulation, or changes in arterial pressure, will activate neurons within these circuits.
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