[PL3]: Molecular mechanisms of synaptic differentiation and selective synapse assembly

This presentation will address the idea that conservation of epigenetic mechanisms for information storage represents a unifying model in biology, with epigenetic mechanisms being utilized for cellular memory at levels from behavioral memory to development to cellular differentiation. The area of epigenetics is unfamiliar to many neurobiologists: epigenetic mechanisms typically involve alterations in chromatin structure, which in turn regulate gene expression. “Epigenetics” is functionally equivalent to the mechanisms allowing stable maintenance of gene expression that involve physically “marking” DNA or its associated proteins through post-translational modification. Thus, regulation of chromatin structure and regulation of direct methylation of DNA are the principal mechanisms of epigenetic regulation. Do epigenetic mechanisms operate in behavioral memory formation? We have generated several lines of evidence that support this idea. (1) Contextual fear conditioning triggers alterations in hippocampal histone acetylation, and contextual latent inhibition training triggers similar but distinct changes in histone acetylation. (2) The methyl-DNA binding protein MeCP2 (the Rett mental retardation syndrome gene product) alters chromatin structure and regulates hippocampal LTP and memory formation. (3) Inhibitors of DNA methylation block both hippocampal LTP and associative learning in vivo. An emerging idea is that the regulation of chromatin structure, mechanistically via histone modification and DNA methylation, may mediate long-lasting behavioral change and learning and memory. We find this idea fascinating because similar mechanisms are used for triggering and storing long-term “memory” at the cellular level, for example when cells differentiate.