| 研究実績の概要 |
To investigate the molecular mechanism underlying the memory formation, previously I found that a transient calcium signaling in specific synapses during learning forms permanent condensate of a set of synaptic proteins, including GluN2B, a subunit of NMDA receptor, Stargazin, auxiliary subunit of AMPA receptor, PSD-95 and Neuroligin-1 (NLGN1), a neuronal adhesion molecule, via the activation of calcium/calmodulin-dependent protein kinase (CaMKII). Also, I have demonstrated that applying the endogenous inhibitors of CaMKII, Camk2n1/2, to the CaMKII-mediated protein condensates disrupt the phase. Interestingly, when the condensate is newly formed, applying Camk2n1/2 only makes the phase shrink, however, when the condensate has been formed for a while, applying Camk2n1/2 breaks down the entire phase. In addition, while less dendritic spines were observed with Camk2n1/2 overexpressed in dissociated hippocampal cultures, increased and smaller spines were observed with knock-out Camk2n1/2. Taken all together, the different resistance to the Camk2n1/2 and the opposite observation of spine number and morphology might be involved in the mechanism for the turnover of synapses, which needs future experiments to clarify in this intriguing phenomenon.
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