Cracking the Synaptic Memory Code

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Despite their role in long-term information storage, synapses are highly dynamic and composed of rather short-lived components. In the adult mouse brain, it takes a couple of days for half dendritic spines to be replaced. Similarly at the molecular level most synaptic proteins have half-lives in the order of a week meaning they constantly need to be replaced by freshly produced ones. Thus, understanding how long-term memory can arise from unstable elements is one of today’s neuroscience’s greatest challenges. Overturning an old dogma, I discovered using in vivo and in vitro approaches that most synapses produce their own proteins locally at both the pre- and postsynaptic sites. Interestingly, classic plasticity paradigms produce unique patterns of rapid pre- and/or postsynaptic translation. This finding is driving a paradigm shift in our understanding of synaptic function. It is now possible to decode pre- and postsynaptic memory traces formed during learning. I am now in the unique position to combine omics, cytometry, super-resolution and live-imaging techniques, and behavioral learning tasks to unravel how local production of new proteins contributes to information storage at synapses. Firstly, using live-imaging, I want to understand how and when protein synthesis is recruited in excitatory boutons. Secondly, using next generation sequencing and imaging, I will investigate how mRNA find their way to presynapses. Finally, using a genetically encoded neuronal activation tracker, I will follow the molecular changes and thus uncover the synaptic memory traces in the hippocampus and cortex after learning. Altogether, these experiments will tackle from molecules to neural networks the unresolved question of memory encoding in the brain. With an unprecedented resolution, we will gain critical insights into how memories are stored at synapses. Such a fundamental understanding of brain function is needed to provide new avenues against neurodegenerative diseases.