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Profiling cell-type-specific transcriptional changes and DNA break sites in response to contextual fear learning

ABSTRACT: Profiling cell-type-specific transcriptional changes and DNA break sites in response to contextual fear learning

PROVIDER: PRJNA648407 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12318500_1.fastq.gz	Fastqsanger.gz
	SRR12318500_2.fastq.gz	Fastqsanger.gz
	SRR12318501_1.fastq.gz	Fastqsanger.gz
	SRR12318501_2.fastq.gz	Fastqsanger.gz
	SRR12318502_1.fastq.gz	Fastqsanger.gz

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Profiling cell-type-specific transcriptional changes and DNA break sites in response to contextual fear learning

Project description:Neuronal activity generates DNA double-strand breaks (DSBs) in vitro and in vivo, and these breaks facilitate the rapid transcriptional induction of immediate early genes (IEGs). Yet the locations of these DSBs in vivo and their relation to brain function remains unclear. Here, following contextual fear conditioning in mice, we profiled the locations of DSBs genome-wide along with transcriptomic changes in neurons and glia in two brain regions. Interestingly, while DSB-susceptible genes induced by fear learning in neurons are predominately involved in synaptic processes, we also observe increased DNA breaks at genes upregulated in glia. Both activity-regulated and proteostasis-related transcription factors appear to govern these gene expression changes across cell types. Finally, we find that glia but not neurons have a robust transcriptional response to glucocorticoids, and these are sites of DSBs. Overall, our data show that fear learning rapidly induces transcriptional changes at genes important for brain function, including stress-responsive genes in glia, and this correlates with hotspots of DSBs.

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Sono-Seq analysis of contextual fear conditioning

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Encoding of Contextual Fear Memory Requires De Novo Proteins in the Prelimbic Cortex

Project description:Time dependent coordinated hippocampal-prefrontal cortical interactions are required for the long-term storage of memories. However, the role of prefrontal cortex (PFC) in encoding of long-term memories remains elusive. Here, we discover a critical role of PFC in the encoding of contextual memories in mice. We demonstrate that specific pools of mRNAs are translated in the PFC following one and six hours of behavioral training. Moreover, disruption of protein synthesis in the prelimbic region of PFC immediately after training inhibits encoding contextual fear memories, whereas disruption at six hours after training is ineffective. Thus, early protein synthesis in the PFC is necessary and critical for the encoding of contextual fear memories. These findings establish key role for the prelimbic cortex in encoding of contextual memories.

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Selection for contextual fear conditioning affects anxiety-like behaviors and gene expression (palme-affy-mouse-84746)

Project description:These data are from the brains (amygdala and hippocampus) of mice originally derived from a cross between C57BL/6J and DBA/2J inbred strains. We used short-term selection to produce outbred mouse lines with differences in contextual fear conditioning, which is a measure of fear learning. We selected for a total of 4 generations. Fear learning differed in the selected lines and this difference was stronger with each successive generation of selection. These mice also showed differences for measures of anxiety-like behavior, but were not different for tests of non-fear motivated learning, suggesting that selection altered alleles that are specifically involved in emotional behaviors. We identified several QTLs for the selection response. We used Affymetrix microarrays to identify differentially expressed genes in the amygdala and hippocampus of mice from the final generation of selection. Amygdala and hippocampus samples were rapidly dissected out of experimentally naïve mice f rom each selected line. Three samples were pooled and hybridized to each array. Experimentally naïve mice were used because the behavior of the mice can be reliably anticipated due to their lineage. Thus, these gene expression differences are not due to the response to human handling, foot shock or fear-inducing conditioned stimuli. We have a second similar study that focuses on a different selected population that was based on C57BL/6J and A/J mice (see GES4034).

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Contextual fear conditioning induced transcriptional changes in hippocampal CA1 neurons

Project description:The goal of our study was to assess whether the experience can regulate specific lncRNAs within the hippocampus and their role in associative memory. To address this, we carried out unbiased analyses of gene expression in CA1-hippocampal neurons to identify lncRNA changes induced by contextual fear conditioning (CFC).

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Adult Female Rat Hippocampal Tissue: Naïve vs. Contextual Fear Conditioned (Trained)[Experiment 1]

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