Long-lasting synaptic plasticity mediated by yin-yang effect of BDNF and proBDNF

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Brain memory is established through 2 steps; acquisition and consolidation, the cellular mechanisms of the former step have been well analyzed using LTP (long-term potentiation) and LTD (long-term depression) as model phenomena for analysis, while those of the latter remain unclear. We previously reported in the stable cultures of hippocampal slice that 3 repeated inductions of LTP and LTD lead to the long-lasting strengthening and weakening of neuronal circuit supported by new synapse formation and elimination, respectively. In the present research, we demonstrated that the synapse formation is mediated by a BDNF (brain-derived neurotrophic factor)-TrkB signaling pathway, while the synapse elimination is mediated by a proBDNF (precursor protein of BDNF)-p75 pathway. Since BDNF and proBDNF are the products of a single gene, the apparently opposite cellular events are regulated by epigenetic regulation, this fact may provoke a paradigm shift in memory research.