The research in this proposal will elucidate mechanisms underlying changes that occur in the functional properties of neurons due to the process of aging. We will focus on a major part of the basal ganglia, the neostriatum, because this ares of the brain is in- volved in pathological conditions associated with aging. We will determine the nature and time-course of the age-related changes in the dopaminergic nigrostriatal connections and their interactions with corticostriatal afferents. In one set of experiments, the effects of the aging process will be determined on the ability of the putative neurotransmitters glutamate, gamma-aminobutyric acid, and dopamine to alter neurophysiological activity of caudate neurons. These experiments will concentrate on demonstrating that dopamine's ability to modulate corticostriatal responses is compromised during aging. The changes in membrane properties of striatal neurons during aging will also be determined. In a second series of experiments immunohistochemical procedures will be used to identify age-related changes in inputs to the striatum from the substantia nigra that contain dopamine and inputs that contain glutamate. The age-related changes of the relationship between dopamine containing synapses and synapses of corticostriatal inputs will be assessed in a final experiment. The studies outlined in this proposal will indicate how neurotransmitter changes during aging are reflected in neuronal function and how they relate to morphological alterations. The information obtained from these studies is important because pathologies in the neostriatum and/or the substantia nigra are involved in age-related neurological disorders exemplified by Parkinson's Disease and Huntington's Disease.
| Cepeda, C; Lee, N; Buchwald, N A et al. (1992) Age-induced changes in electrophysiological responses of neostriatal neurons recorded in vitro. Neuroscience 51:411-23 |
| Walsh, J P; Cepeda, C; Hull, C D et al. (1989) Dye-coupling in the neostriatum of the rat: II. Decreased coupling between neurons during development. Synapse 4:238-47 |
| Cepeda, C; Walsh, J P; Hull, C D et al. (1989) Intracellular neurophysiological analysis reveals alterations in excitation in striatal neurons in aged rats. Brain Res 494:215-26 |
| Cepeda, C; Walsh, J P; Hull, C D et al. (1989) Dye-coupling in the neostriatum of the rat: I. Modulation by dopamine-depleting lesions. Synapse 4:229-37 |
