DESCRIPTION (Investigator's Abstract): During recent years of support from this grant the applicant has focused on immunocytochemistry for amino acids within synaptic terminals of identified descending cortical pathways as a better indicator of the neurotransmitter pool of an amino acid than the autoradiographic or immunocytochemical identification combined with anterograde tracing at the electron microscopic level, thus permitting quantification of the density of amino acids in an identified population of synaptic endings. The principal investigator found that corticofugal terminals in the thalamus, dorsal column nuclei and spinal cord were enriched with glutamate, though the density of gold particles coding for this amino acid was variable. Some terminals were also enriched with aspartate but little correlation existed between the density of particles coding for glutamate and for aspartate in the same terminal, implying that corticofugal terminals may be enriched with one amino acid but not the other. From this research it has become apparent that the cerebral cortex exerts its control by way of glutamatergic pathways even though the role of its modulation may vary in different subcortical structures. Different effects of cortical control may be mediated by different glutamate receptors especially where their control is exerted on a pool of excitatory neurons, e.g. in the ventrobasal complex (VB) of the thalamus versus a pool of inhibitory neurons, e.g. in the reticular nucleus, both parts of thalamic circuits. The main focus of the proposed research is to explore this possibility. The applicant will determine the subunit composition of glutamate receptors at the ending of corticothalamic fibers in VB and in the reticular nucleus. In addition, the applicant will also determine the co-existence of different glutamate receptors (AMPA, NMDA and metabotropic) at the same cortical synapse in VB and reticular nucleus, as well their topographic arrangement and presynaptic versus postsynaptic location.