The neurochemical anatomy and synaptic interactions of pathways in the central nervous system that control the baro- and chemoreceptor reflexes are incompletely understood. Several competing hypotheses indicate that glutamate, substance P, or neuropeptide Y may be the neurotransmitter(s) contained in primary afferent baro- and chemoreceptor terminals, and/or in second order cardiorespiratory perikarya in the nucleus tractus solitarius (NTS). However, there is no ultrastructural proof of these hypotheses. Another hypothesis suggests that GABAergic terminals in the NTS mediate presynaptic inhibition of the baroreceptor reflex. In the proposed research we will use electron microscopic immunocytochemistry with colloidal gold, and peroxidase histochemistry to obtain ultrastructural proof of the following critical questions: 1) What is (are) the neurotransmitter(s) contained within primary afferent terminals which originate in the carotid sinus and carotid body, and transmit baro- and chemoreceptor reflex information into the NTS? 2) What is (are) the neurotransmitter(s) contained within second order neurons of the NTS which receive and relay baro- and chemoreceptor signals? 3) What neurotransmitter(s) is (are) contained within NTS neurons which modulate baroreceptor afferent terminals? These experiments will provide the first ultrastructural evaluations of at least seven important hypotheses on the neurochemical circuitry of the baro- and chemoreceptor reflexes. These data will help us to understand the central mechanisms which influence blood pressure and respiration.