Muscarinic cholinergic receptor (mR) activation has robust effects on long-term memory storage, physiological plasticity and can induce immediate early gene (lEG) expression. This study will investigate the relationship between mR effects on memory and lEG expression. Rats will be trained in an inhibitory avoidance paradigm. Avoidance of the shock-associated compartment will be the major index of retention. Some rats will be sacrificed after training to allow analysis of effects of memory enhancing posttraining mR agonism on mRNA induction of the lEGs EGR-1, c-fos and Arc and the phosphorylation of ERK1/2 during memory consolidation. Experiment I will include broad analysis of systemic post-training mR effects, including effects in neocortex, hippocampus and amygdala. Experiment II will employ temporary inactivation of major cholinergic basal forebrain regions after training to investigate the contributions of endogenous cholinergic release during consolidation to long-term memory, lEG expression and ERK1/2 activation. Experiment III will investigate which signaling cascades (e.g., protein kinases) are involved in effects of mR activation on memory and immediate early gene expression.
