The neuropeptide galanin is localized in the hippocampus, coexists with acetylcholine in the rat septohippocampal pathway, coexists with norepinephrine in the locus coeruleus, and inhibits the release of glutamate, acetylcholine, and norepinephrine. Galanin is overexpressed in the basal forebrain in Alzheimer's disease. Our laboratory is engaged in investigating the behavioral concomittants of the inhibitory effects of galanin on neurotransmitters necessary for cognitive processes. Our experiments have revealed that galanin administration to rats impairs performance on several memory tasks. Last year, postdoctoral fellow Terri Gleason set up the Morris water task, to test the actions of galanin in this widely used spatial learning test. Intraventricularly administered galanin induced performance deficits primarily on selective quadrant search during the probe trial. Significant genetic components were detected in responsiveness to galanin. The Wistar and Sprague-Dawley strains were sensitive to the inhibitory actions of galanin, as compared to the Long-Evans strain which was unaffected by galanin treatment in this task. Performance on the visible platform task and in Digiscan exploratory locomotion was normal at doses of galanin which impaired acquisition of the Morris water task using spatial environmental cues. PUBLICATION: Gleason TC, Dreiling JL, Crawley JN (1999) Rat strain differences in response to galanin on the Morris water task. Neuropeptides 33:265-270.Postdoctoral fellow Jeff Kinney initiated an investigation into the nature of the galanin-induced deficit on the Morris task. Aquisition versus retention effects of galanin were compared. Intraventricularly microinjected galanin produced deficits on probe trial performance in Sprague-Dawley rats when galanin was administered either before or after the training sessions. Time-course analysis revealed that galanin administration at time points of 5 minutes, 30 minutes, and 3 hours after the end of the daily training sessions completely abolished selective quadrant search. Performance on the probe trial was normal when galanin was administered 18 hours after the training trials. This exciting finding indicates that galanin has a direct inhibitory action on biochemical processes necessary for memory consolidation. This year our galanin research program received a new research tool. Galanin overexpressing transgenic mice were generated on a dopamine beta hydroxylase promoter by Robert Steiner and coworkers at the University of Washington, Seattle. The chimera line was backcrossed for 7 generations into a C57BL/6J background for our behavioral experiments. Postdoctoral fellow Andrew Holmes and several student volunteers conducted the first behavioral phenotyping on galanin transgenic mice and their wild type control littermates. General health, home cage behaviors, neurological reflexes, and motor functions were normal. Impaired performance on the Morris water task was found in the galanin transgenic mice at ages 8, 16, and 24 months. The profile of the behavioral deficits was similar to that seen in rats given exogenous galanin. Normal performance on the visible and hidden platform components were followed by lack of selective search on the probe trial. Postdoctoral fellow Craige Wrenn tested the galanin transgenic mice on a second memory task, social transmission of food preference. Wild type littermate control mice showed the expected preference for a food scented with a flavor previously consumed by a cagemate 24 hours earlier. The galanin transgenic mice did not show a preference for consuming the food containing the socially transmitter odor cue, as compared to consumption of food containing a novel odor. Poor performance by the galanin transgenics on this olfactory memory task supports the results of the Morris spatial navigation task, confirming a cognitive deficit in the galanin overexpressing mice. Evaluation of learning and memory in the galanin overexpressing transgenic line is proceeding. Experiments generating the initial findings are being repeated with a new batch of mice, and using additional behavioral tasks.
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