The effects of galanin on long-term synaptic plasticity in the CA1 area of rodent hippocampus.

Learning and memory involve complex changes in neuronal excitability including long-lasting synaptic plasticity of glutamatergic synapses. The observation that the neuropeptide galanin affects performance in a number of behavioural models predicts that galanin should affect synaptic processes underlying learning. The present study in rat and mouse hippocampal slices now demonstrates that galanin inhibits long-term potentiation induced by both tetanic and theta-burst stimulation in both apical and basal dendrites of CA1 pyramidal neurones but does not affect long-term depression. This selective effect on long-term potentiation does not appear to be mediated through inhibition of N-methyl-D-aspartate or metabotropic glutamate receptor function, but likely resides downstream of receptor activation, possibly at the level of the kinase cascade that converts short-term into long-term potentiation. Our results indicate possible mechanisms by which the neuropeptide galanin may act at the molecular level to influence learning and memory in vertebrates.

Galanin regulates the postnatal survival of a subset of basal forebrain cholinergic neurons.

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.