The proposed research continues to focus on neurons containing catecholamines and/or opioid peptides in brain regions where they have been most implicated in adverse autonomic and emotional responses to stressful stimuli. Electron microscopic immunocytochemical dual labeling will be used to determine the subcellular and/or synaptic basis for functional interactions between these chemically specific neurons in rat brain. Additionally, the proposed use of molecular probes and quantitative morphometric methods will extend the candidate's level of expertise while providing information that complements the ultrastructural studies. Study I proposes to examine the synaptic circuitry between neurons containing catecholamine synthesizing enzymes, GABA, or specific opioid peptides in portions of the dorsal vagal complex receiving peripheral input from sensory afferents and circulating hormones. The nuclei of the solitary tracts (NTS) also will be examined by combining anterograde transport, anterograde degeneration, and immunocytochemical methods to determine whether there is a cellular substrate for convergent input from descending limbic (prefrontal cortex and amygdaloid) and sensory vagal afferents. The role of vagal afferents in determining more long term changes in the levels of transmitter synthesizing enzymes, neuropeptides and/or their corresponding mRNA's also will be examined in the NTS. Study II proposes to examine the cellular relationships between dopaminergic afferents and chemically specific, largely inhibitory, neurons in the striatum (caudate-putamen and accumbens nuclei). The possibility that the opposing actions of dopamine and acetylcholine may reflect cholinergic modulation of an excitatory system also will be examined. Study III proposes to examine the cellular substrate for GABAergic or peptidergic modulation of dopaminergic neurons that contribute efferents to targets in the prefrontal cortex, amygdaloid nuclei, and nucleus accumbens. In studies II-III, animals receiving chronic haloperidol will be examined to determine whether there are regionally or chemically specific ultrastructural changes that suggest a basis for the beneficial or movement related side effects of typical antipsychotic drugs. Study IV proposes to examine chemically specific subsets of neurons in the adult striatum following unilateral neonatal chemical lesions of dopaminergic afferents. The goal is to evaluate dopamine's role in regulation of the phenotypic expression of transmitters and/or ultrastructure of target neurons. The results from these four studies should provide information that will be useful in understanding the pathogenesis or in designing new therapeutic measures to treat human autonomic, psychiatric, and movement disorders arising from imbalances of specific transmitter systems.
