The elucidation of memory phenomena has thus far been conducted with methods that involve brain tissue destruction, drug administration, or genetic modification, which are problematic in terms of reversibility and cell specificity. To overcome these problems, the development of techniques that utilize a light-sensitive channel has been actively pursued. This approach, however, suppresses activity of all cells, so not only are synapses that are actually involved in memory formation suppressed, but those that are unrelated to this event are also affected.
Therefore, based on our previous LTP (long-term potentiation) studies, we aim to develop a method in which the principle is applied to restore LTP. We showed that the size of synapses underwent LTP is increased due to actin polymerization. When this occurs, cofilin binds to actin filaments at a high density. Whereas the function of cofilin to depolymerize actin filaments is well known, cofilin is also known to stabilize—rather than destabilize—actin filaments depending on the circumstances. Our findings likely reflect this effect and point to the idea that the inactivation of cofilin in some ways may lead to the erasure of LTP. To this end, we will try to inactivate cofilin via light, using chromophore-assisted light inactivation (CALI). So far we could suppress LTP. But it has not been possible to ‘undo’ LTP in synapses in which LTP has already been induced, without affecting other synapses. This study is promising in the sense that a new approach to learning and memory research will be revealed.
Yasunori HAYASHI
Graduate School of Medicine Kyoto University
