2000•Proceedings of the National Academy of SciencesOpen access
Galanin regulates the postnatal survival of a subset of basal forebrain cholinergic neurons
Gillian F. O’Meara, Urania Coumis, Shuang Y. Ma, Ján Kehr, Sally Mahoney, Andrea Bacon, Shelley Allen, Fiona E. Holmes, Ulrika Kahl, Fu H. Wang, Ian R. Kearns, Sven Ove-Ogren, David Dawbarn, Elliott J. Mufson, Ceri H. Davies, Gerard R. Dawson, David Wynick
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Abstract
The neuropeptide galanin colocalizes with choline acetyltransferase, the synthetic enzyme for acetylcholine, in a subset of cholinergic neurons in the basal forebrain of rodents. Chronic intracerebroventricular infusion of nerve growth factor induces a 3- to 4-fold increase in galanin gene expression in these neurons. Here we report the loss of a third of cholinergic neurons in the medial septum and vertical limb diagonal band of the basal forebrain of adult mice carrying a targeted loss-of-function mutation in the galanin gene. These deficits are associated with a 2-fold increase in the number of apoptotic cells in the forebrain at postnatal day seven. This loss is associated with marked age-dependent deficits in stimulated acetylcholine release, performance in the Morris water maze, and induction of long-term potentiation in the CA1 region of the hippocampus. These data provide unexpected evidence that galanin plays a trophic role to regulate the development and function of a subset of septohippocampal cholinergic neurons.