TRANSPLANTATION OF CHOLINERGIC NERVE CELLS

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Recent studies of fetal transplants containing cholinergic nerve cells of the rat septal nucleus have shown that the transplants have the capacity to innervate the hippocampal formation of recipient rats. The pattern of reinnervation appears to be quite specific and mimics the pattern produced by intrinsic septal afferents. Electrophysiological studies suggest that the transplant-derived innervation forms functional connections. This notion is further supported by behavioral studies that have demonstrated a recovery of maze learning abilities by rats with septal tissue transplanted into the denervated hippocampal formation. These studies in conjunction with other transplantation studies have led to the proposed use of neural transplants in the treatment of neurological disorders that stem from the degeneration specific neuronal populations. We propose to determine whether alternate sources of cholinergic nerve cells from the peripheral and central nervous system can innervate the hippocampal formation and form functional connections. Ciliary ganglia, ventral spinal cord, and basal nuclei from fetal rats; and ciliary ganglia and basal nuclei from adult rats will be grafted or implanted as cell suspensions into the hippocampal formation of adult rats. Evidence for the cholinergic innervation of the hippocampus will be obtained from histochemical methods to reveal acetycholinesterase and choline acetyltransferase localization and from assays to determine choline acetyltransferase activity. The functional nature of the transplant-derived innervation will be assessed by electrically stimulating the transplant and recording the evoked responses within the hippocampal formation, and by analyzing the slow- wave activity in behaving animals. Recovery of behavioral function will be determined by assessing the T-maze and water maze learning abilities of rats with and without transplants. These studies will determine whether alternate sources of cholinergic nerve cells can innervate target sites in the host hippocampal formation and restore functions normally mediated by cholinergic septal fibers.