Gene Expression in Long-term Memory

Icahn School Of Medicine At Mount Sinai, New York NY

Investigators

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Abstract

DESCRIPTION (provided by applicant): Newly acquired information becomes a long-lasting memory through a process known as memory consolidation, which depends upon gene transcription and translation. The overall goal of this project is to elucidate the nature of the molecular pathways underlying memory consolidation using inhibitory avoidance (IA) as a memory task in rats. Previously, the PI's laboratory has discovered and characterized the fundamental role of the transcription factors CCAAT enhancer binding protein (C/EBP) beta and delta in the hippocampus during IA memory consolidation. The recent identification of some of the downstream genes regulated following the induction of C/EBP during memory consolidation together with other preliminary studies ongoing in the PI's laboratory led to the proposal of a novel, integrated working hypothesis for why these transcription factors have been evolutionarily selected to mediate long-term memory formation. To test this hypothesis, 3 specific Aims will be addressed: AIM 1) To determine whether the role of C/EBPs in the hippocampus during memory consolidation is recruited through the activation of survival pathways in response to adaptive stress. AIM 2) To determine whether the activation of survival pathways induces an autoregulation of the CREB- C/EBP pathway in the hippocampus during memory consolidation. AIM 3) To determine whether C/EBPb and/or C/EBPd are directly involved in the regulation of the expression of genes, such as the tyrosine kinase receptor MuSK, that are believed to mediate synapse formation and/or survival (maintenance) in the adult brain. The understanding of how stress and survival pathways mediate memory formation will likely provide key information for developing novel strategies for the treatments of several pathologies, including cognitive and memory formation disorders, neurodegeneration and affective disorders.