Dataset Information

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

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".

SUBMITTER: Simbriger K

PROVIDER: S-EPMC7859833 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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

Simbriger Konstanze K Amorim Inês S IS Lach Gilliard G Chalkiadaki Kleanthi K Kouloulia Stella S Jafarnejad Seyed Mehdi SM Khoutorsky Arkady A Gkogkas Christos G CG

Progress in neurobiology 20200826

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 h ...[more]

PMID: 32860876

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Project description:A fundamental question in neuroscience is how memories are stored and retrieved in the brain. Many neurological, psychiatric and neurodevelopmental disorders are associated with cognitive deficits. Therefore characterizing the biological basis of these processes is critical for understanding normal and abnormal brain function. It is known that long-term memory formation requires transcription and translation as well as epigenetic processes that control gene expression. In this study we examined genome-wide gene expression changes during memory consolidation and after memory retrieval. We observe the largest changes in gene expression 30 minutes after memory acquisition and retrieval, and several novel genes were found to be affected by both. Interestingly, acquisition and retrieval of memory down-regulate different processes. Chromatin assembly is down-regulated after memory acquisition whereas RNA processing is down-regulated so after retrieval. Histone variant H2AB levels are reduced following acquisition, while splicing factor Rbfox1 and NMDA receptor-dependent microRNA miR-219 are down-regulated following retrieval. We also show that miR-219 down-regulation after retrieval is accompanied by up-regulation of its target protein CAMKIIÎ³. Our study highlights for the first time the differential involvement of epigenetic mechanisms that control gene expression, such as histone variants and post-transcriptional RNA processing, during memory acquisition and retrieval. 72 total samples were analyzed, including animals trained in a contexual conditioning paradigm (FC) and controls. Tissue was collected at 30 minutes (FC30), 4 hours (FC4), 12 hours (FC12) and 24 hours after FC (FC24) as well as 30 minutes after testing for retrieval of the memory (RT30). Testing was performed at 24 hours after training over a 5-minute interval. Animals that were handled but not trained were dissected at the same time of day to control for variations due to circadian rhythms (CC30, CC4 andCC12). The protocol was repeated over the course of 2 weeks to obtain 9 animals (2 hippocampi) per group, so that 9 independent FC experiments were represented in each time point and all animals for each group were dissected at the exactly the same time of day.

Dataset Information

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

Publications

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

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