Studies of effects of perinatal hypoxia-ischemia on developing central neurotransmitter circuits will be continued using the one-week-old rat pup preparation which we have characterized. Based on previous work, we hypothesize, that cholinergic interneurons in striatum are especially vulnerable to hypoxia-ischemia but they regenerate later in life. We will test this hypothesis by examining the response of cholinergic neurons to injury and recovery using cholinergic biochemical markers and immunohistochemical staining for choline acetyltransferase. Work over the last year indicates that major reorganizational charges occur in the distribution and density of neurotransmitter receptors in the immature striatum damaged by hypoxia-ischemia. Moderate damage to the immature striatum leads to an increase in the density of GABAergic receptors in the striatum and in regions receiving striatal projections, and the mechanisms for these changes will be explored. Results in press suggest that hypoxia-ischemia severe enough to trigger tissue injury is associated with a massive release of dopamine in the immature striatum. We plan to test the hypothesis that this release, as well as tissue injury, can be reversed by calcium antagonist drugs.
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