Molecular mechanisms for plasticity of hippocampal synaptic transmission

Although the NMDA receptor plays an essential role in the induction of long-term potentiation (LTP) in the CA1 region of the hippocampus, which is thought to underlie some types of learning and memory, there are many other functional molecules that regulate the induction and expression of LTP. Examining knockout mice lacking a certain gene, we found that some molecules, including nociceptin receptors, cadherin 11, telencephalin and H-Ras, inhibit synaptic plasticity in normal animals. In nociceptin receptor-deficient mice, both LTP and memory are enhanced without apparent changes in basal synaptic transmission. In mice lacking either cadherin or telencephalin, LTP is facilitated and some behavioral abnormalities are observed. In H-ms-deficient mice, tyrosine phosphorylation of NMDA receptors is increased, and correspondingly, NMDA synaptic responses are potentiated, which results in an enhancement of LTP. The lack of these four molecules causes an enhancement of LTP, presumably through different mechanisms, and these results suggest that plastic changes in the central nervous system (CNS) are regulated by variant intracellular biochemical pathways.