Lecture 18: Learning and Memory: Long-term Potentiation in the Mammalian Hippocampus

PRIMARY MESSAGE: The idea that synaptic long-term potentiation (LTP) is the substrate of learning remains controversial. Nevertheless, several lines of evidence have linked it to memory, particularly spatial memory in rats. Induction of LTP is via a postsynaptic calcium signal generated through glutamate NMDA receptors. Expression is mediated by phosphorylation of pre-existing AMPA receptors and mobilization of new AMPA receptors via a biochemical cascade through calcium/calmodulin-dependent protein kinase II (CaMKII). Stabilization of LTP requires protein synthesis via the cyclic AMP response element binding protein (CREB). Genetic knockout experiments in mice (CaMKII, and NMDAR knockouts) strongly suggest a role for hippocampal LTP in spatial memory as tested using the Morris water maze.