A decline in motor control and coordination is one of many behavioral manifestations of aging. Whether functional and neurochemical changes in areas of the central nervous system involved in movement control can account for this manifestation of senescence is not known. The rat neostriatum is one structural counterpart of the basal ganglia of man involved in movement control, and the cholinergic system of the neostriatum is one neurotransmitter system involved in motor control and coordination. Our long-term objectives are to describe aged-related functional and neurochemical changes in the cholinergic system of the rat neostriatum. Neostriatal slices will be used for in vitro electrophysiological, neurochemical, and pharmacological studies. Whether presynaptic muscarinic modulation of acetylcholine (ACh) release is altered in aged rats will be examined by testing effects of muscarinic agonists and antagonists on spontaneous and potassium-stimulated ACh release. In order to ascertain the functional significance of any changes in the neurochemical studies, the muscarinic drugs will be tested for their effects on synaptic population spikes. By means of intracellular recordings, age-related changes in nicotinic excitatory postsynaptic potentials (EPSPs) will also be examined. Parameters that will be examined in electrophysiology studies include the latency, rise time and amplitude of evoked responses, and membrane resistance and potential changes. Finally, the effects of choline on muscarinic modulation of ACh release and nicotinic EPSPs will be tested. The significance of this research is that both neurochemical and functional age-related changes in the cholinergic system of the rat neostriatum will be examined. The research might establish whether 1) the cholinergic system specifically in the neostriatum undergoes age-related changes, 2) there are age-related changes in sensitivity of this cholinergic system to presynaptic muscarinic modulation of ACh release, and 3) choline has any age-related effects on the cholinergic system in the neostriatum. Moreover, changes in the neostriatal cholinergic system of the elderly might implicate that therapeutic regimes for the elderly should be re-evaluated.
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