Understanding how and where our memory is stored is a long sought-after task. It is accepted that proteins at synapses play a role in capturing and maintaining memory. It is now clear that synapses possess the capacity for local protein synthesis, and that dendritic protein synthesis is required for many forms of long-term synaptic potentiation (LTP) and plasticity.
It remains unclear over what spatial scale local translation can be regulated and stimulated. Moreover, the location of specific translation sites and the mechanisms by which local dendritic translation is activated are largely unknown.
This study aims to determine the effect of single spine activity on local protein synthesis, and to decipher how varying levels of activation of the synapse activity in adjacent spines alters the dynamics and trafficking of newly synthesized proteins and to what extent (spatially and temporally).
I will examine the correlation between local translation and the following neurobiological processes: synaptic plasticity, LTP, and the hypothesis of synaptic tagging and capturing. Their activation will be induced using different levels and patterns with high resolution glutamate uncaging, in adjacent or remote spines including on different dendritic branches.
I propose to decipher the location of protein synthesis using fluorescent non-canonical amino acid tagging, which allows visualizing the protein synthesis in real time and in its natural site. I will address the translational regulation of exemplar proteins, of which their mRNAs were found to localize in dendrites, that represent neurotransmitter receptors (e.g. GluA1 or 2), scaffolding molecules (e.g. Shank, PSD-95), signaling molecules (e.g. CaMKIIa) and cytoskeletal elements (e.g. b-actin).
Understanding the spatial and temporal synthesis of proteins following different levels and patterns of spinal activity will shed light on the mechanisms by which important cell biology processes including LTP and plasticity occur.
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