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Uncovering memory-related gene expression in contextual fear conditioning using ribosome profiling.

Simbriger, K; Amorim, IS; Lach, G; Chalkiadaki, K; Kouloulia, S; Jafarnejad, SM; Khoutorsky, A; (2020) Uncovering memory-related gene expression in contextual fear conditioning using ribosome profiling. Progress in Neurobiology , Article 101903. 10.1016/j.pneurobio.2020.101903. (In press). Green open access

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Abstract

Contextual fear conditioning (CFC) in rodents is the most widely used behavioural paradigm in neuroscience research to elucidate the neurobiological mechanisms underlying learning and memory. It is based on the pairing of an aversive unconditioned stimulus (US; e.g. mild footshock) with a neutral conditioned stimulus (CS; e.g. context of the test chamber) in order to acquire associative long-term memory (LTM), which persists for days and even months. Using genome-wide analysis, several studies have generated lists of genes modulated in response to CFC in an attempt to identify the "memory genes", which orchestrate memory formation. Yet, most studies use naïve animals as a baseline for assessing gene-expression changes, while only few studies have examined the effect of the US alone, without pairing to context, using genome-wide analysis of gene-expression. Herein, using the ribosome profiling methodology, we show that in male mice an immediate shock, which does not lead to LTM formation, elicits pervasive translational and transcriptional changes in the expression of Immediate Early Genes (IEGs) in dorsal hippocampus (such as Fos and Arc), a fact which has been disregarded by the majority of CFC studies. By removing the effect of the immediate shock, we identify and validate a new set of genes, which are translationally and transcriptionally responsive to the association of context-to-footshock in CFC, and thus constitute salient "memory genes".

Type: Article
Title: Uncovering memory-related gene expression in contextual fear conditioning using ribosome profiling.
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.pneurobio.2020.101903
Publisher version: https://doi.org/10.1016/j.pneurobio.2020.101903
Language: English
Additional information: Under a Creative Commons license: Attribution 4.0 International (CC BY 4.0)
Keywords: Memory, fear conditioning, translational profiling
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Lab for Molecular Cell Bio MRC-UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10109166
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