Abstract
To understand molecular mechanisms of learning and memory is one of major topics in neuroscience research. To identify genetic components underlying synaptic plasticity and memory processes, I have been so far focusing on analyzing behavioral phenotypes, especially learned fear, of several strains of genetically manipulated mice for plasticity-related genes. One example is Fyn-overexpressing mice exhibiting hyper-tyrosine-phosphorylation of the NMDA receptor (NR). These mice showed NR activity-dependent impairment of fear conditioning, suggesting that this tyrosine kinase is a key molecule that controls conditioned fear through NR phosphorylation. Another is knockout (KO) mice for drebrin A, a F-actin binding protein in the dendritic spines. Context-dependent fear conditioning and MK-801-induced hyperlocomotion were changed in these KO mice. These results suggest that drebrin A has a pivotal role in the regulatory mechanism of NR function. The mutant mice for ICER, a CRE-binding transcriptional repressor, also showed the phenotype on fear conditioning. In ICER-overexpressing mice, long-term retention of fear memory was impaired, while the short-term memory remained intact. ICER-KO mice conversely showed a better performance in the retention of conditioned fear. These results suggest that ICER acts as a negative regulator for memory consolidation. Thus, these three examples demonstrate that the learned fear is a good target of behavioral analysis of mutant mice for genes being critical for synaptic plasticity and it should be included in the behavioral test battery. [J Physiol Sci. 2006;56 Suppl:S51]
