DESCRIPTION: (Applicant's abstract) Cerebrovascular disease (stroke) is the third leading cause of death, and the number one cause of disability in the United States. The applicant's long-term goal is to identify mechanisms of neuronal damage following transient cerebral ischemia CA1 neurons in hippocampus and spiny neurons in neostriatum are highly vulnerable to transient forebrain ischemia. The current knowledge about the pathogenesis of post-ischemic neuronal injury is mainly derived from studies on hippocampal neurons. Little is known about the neurophysiological changes in striatal about the neurophysiological changes of striatal neurons following ischemia. The temporal threshold for injury and the time course of cell loss differ dramatically between hippocampus and neostriatum. The mechanisms underlying the neuronal injury in these two regions may not be the same. Studies have shown that the synaptic transmission of CA1 neurons enhances after lethal ischemia. It has also been shown that depletion of dopamine neurons dramatically reduces the post-ischemic neuronal damage in neostriatum. The working hypothesis of this proposal is that dopamine neurons dramatically reduces the post-ischemic neuronal damage in neostriatum. The working hypothesis of this proposal is that dopamine aggravates the post-ischemic neuronal injury by potentiating glutamate excitoxicity. The experiments in this proposal are designed to determine: 1) Whether the synaptic transmission of spiny neurons if facilitated after ischemia and thereby cause neuronal injury; 2) How dopamine potentiates the synaptic transmission and aggravates the neuronal damage after ischemia. The specific aims of the proposed experiments are: To compare the synaptic transmission of spiny neurons in neostriatum before and after 22 min forebrain ischemia. 2. To study the synaptic transmission of interneurons in neostriatum before and after 22 min ischemia and compare with that of spiny neurons. 3. To analyze the post- ischemic neurophysiological changes of spiny neurons after dopamine depletion and compare with those in intact neostriatum. 4. To determine the mechanisms of asymmetrical protection of striatal neurons against ischemia after dopamine depletion. The results of the proposed experiments will identify the electrophysiological changes correlated with the selective neuronal injury in neostriatum following forebrain ischemia and improve our understanding of the mechanism of brain damage upon resuscitation following cardiac arrest.