OCOCAMKS SIGNED

Project "OCOCAMKS" data sheet

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 Partnership

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 Project objective

How are memories formed and stored in the brain? One candidate mechanism is long term potentiation (LTP), a form of synaptic plasticity that is characterized by strengthening of synaptic connections between neurons in the brain, lasting from minutes to hours. The first step in LTP is a sharp influx of calcium ions, which serves to activate many Ca2-dependent proteins, one of which is Calcium-calmodulin-dependent protein kinase II (CaMKII). Once activated, CaMKII translocates to the post-synapse, and phosphorylates numerous substrate responsible for LTP induction. Curiously, CaMKII also has a role in specifying cellular structure by bundling actin. After activation, CaMKII activity apparently becomes Ca2-independent, and can last for hours after the initial stimulation. This property of CaMKII lead the researchers to propose that CaMKII, in addition to induction of LTP, could also be responsible for LTP maintenance and hence memory storage. I propose to study the role of CaMKII in both the induction and maintenance of LTP in neurons. For this purpose, I plan to generate variants of CaMKII that can be acutely controlled by light. Using the tools I develop, I will investigate the interplay between CaMKII function and structure with respect to LTP and other neuronal processes. This approach offers unprecedented molecular, spatial and temporal control over CaMKII activity in neurons, allowing a better understanding of its involvement in learning and memory.