This ia a proposal for continuation of ongoing research examining the synaptic circuitry in the mature (Study I) and developing (Study II) rat striatum. The objectives in Study I are to determine the synaptic relationships between: (1) dopaminergic afferents from the substantia nigra and intrinsic striatal neurons containing gamma-aminobutyric acid (GABA), opioid peptides (Met-and Leu-enkephalin), and acetylcholine; (2) cholinergic neurons and medium spiny neurons containing GABA or opioid peptides; (3) cortical afferents and neurons containing one or more of the three intrinsic transmitters. The major aims in Study II are to determine whether removal of dopaminergic afferents by 6-hydroxdopamine in the early postnatal period alters the regional densities of immunoreactivity for transmitters in intrinsic neurons; the density or distribution of cortical afferents; or the ultrastructural morphology of targets neurons or terminals in the mature striatum. The primary method to be used in these studies is electron microscopic immunocytochemistry with peroxidase, and radio-iodinated markers for identification of one or more antigens in single sections of tissue. The results from the two studies should be complimentary and broaden our knowledge of interactions between three major types of intrinsic striatal neurons and their synaptic relation to dopaminergic and cortical afferents. This information is important for further understanding the etiology and for developing improved therapeutic measures for a number of movement disorders including Parkinson's disease and Huntington's chorea.
