Identification of the memory signature: gene expression patterns underlying synapse strengthening and weakening

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Changes in gene expression are necessary to strengthen or weaken synaptic connections between neurons. This is especially important in memory encoding circuits within high-level brain regions. In the hippocampus, long-term synapse strengthening (potentiation) and weakening (depression) promote remembering and forgetting, respectively. Both processes occur in response to specific patterns of neuronal activity. Many individual molecules involved in one or the other process have been identified, but a comprehensive unbiased “memory signature” of gene expression necessary for synapse strengthening or weakening is lacking. We aim to define the gene expression patterns associated with strengthened or weakened memory circuits, by sequencing neuronal tissue in which synapses have been strengthened or weakened by distinct patterns of neuronal activity that are causally related to memory. This knowledge could then be exploited to assess circuit and brain states, and to test possible therapeutic interventions that rescue weak synapses (in cognitive decline and neurodegenerative disease, for example) or dampen over-active synapses.