Engram-specific transcriptome profiling of contextual memory consolidation
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA529794 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR8809610.fastq.gz | Fastqsanger.gz | |||
| SRR8809620.fastq.gz | Fastqsanger.gz | |||
| SRR8809630.fastq.gz | Fastqsanger.gz | |||
| SRR8809640.fastq.gz | Fastqsanger.gz | |||
| SRR8809611.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 38 |
Similar Datasets
Project description:Sparse populations of neurons in the dentate gyrus (DG) of the hippocampus are causally implicated in the encoding of contextual fear memories. However, engram-specific molecular mechanisms underlying memory consolidation remain largely unknown. Here we perform unbiased RNA sequencing of DG engram neurons 24h after contextual fear conditioning to identify transcriptome changes specific to memory consolidation. DG engram neurons exhibit a highly distinct pattern of gene expression, in which CREB-dependent transcription features prominently (P=6.2x10-13), including Atf3 (P=2.4x10-41), Penk (P=1.3x10-15), and Kcnq3 (P=3.1x10-12). Moreover, we validate the functional relevance of the RNAseq findings by establishing the causal requirement of intact CREB function specifically within the DG engram during memory consolidation, and identify a novel group of CREB target genes involved in the encoding of long-term memory.
2019-03-30 | GSE129024 | GEO
Project description:Post-learning sleep plays an important role in hippocampal memory processing, including contextual fear memory (CFM) consolidation. Here, we used targeted recombination in activated populations (TRAP) to label context-encoding engram neurons in the hippocampal dentate gyrus (DG) and assessed reactivation of these neurons during post-learning sleep. We find that post-learning sleep deprivation (SD), which impairs CFM consolidation, selectively disrupts reactivation in inferior blade DG engram neurons. This change was linked to more general suppression of neuronal activity markers in the inferior, but not superior, DG blade by SD. To further characterize how learning and subsequent sleep or SD affect these (and other) hippocampal subregions, we used subregion-specific spatial profiling of transcripts and proteins. We found that transcriptomic responses to sleep loss differed greatly between hippocampal regions CA1, CA3, and DG inferior blade, superior blade, and hilus. Critically, learning-driven transcriptomic changes, measured 6 h following contextual fear learning, were limited to the two DG blades, differed dramatically between the blades, and were absent from all other regions. Similarly, protein abundance in these hippocampal subregions were differentially impacted by sleep vs. SD and by prior learning, with the majority of alterations to protein expression restricted to DG. Together, these data suggest that the DG plays an essential role in the consolidation of hippocampal memories, and that the effects of sleep and sleep loss on the brain are highly subregion-specific, even within the DG itself.
2024-03-01 | GSE229080 | GEO
Project description:Post-learning sleep plays an important role in hippocampal memory processing, including contextual fear memory (CFM) consolidation. Here, we used targeted recombination in activated populations (TRAP) to label context-encoding engram neurons in the hippocampal dentate gyrus (DG) and assessed reactivation of these neurons during post-learning sleep. We find that post-learning sleep deprivation (SD), which impairs CFM consolidation, selectively disrupts reactivation in inferior blade DG engram neurons. This change was linked to more general suppression of neuronal activity markers in the inferior, but not superior, DG blade by SD. To further characterize how learning and subsequent sleep or SD affect these (and other) hippocampal subregions, we used subregion-specific spatial profiling of transcripts and proteins. We found that transcriptomic responses to sleep loss differed greatly between hippocampal regions CA1, CA3, and DG inferior blade, superior blade, and hilus. Critically, learning-driven transcriptomic changes, measured 6 h following contextual fear learning, were limited to the two DG blades, differed dramatically between the blades, and were absent from all other regions. Similarly, protein abundance in these hippocampal subregions were differentially impacted by sleep vs. SD and by prior learning, with the majority of alterations to protein expression restricted to DG. Together, these data suggest that the DG plays an essential role in the consolidation of hippocampal memories, and that the effects of sleep and sleep loss on the brain are highly subregion-specific, even within the DG itself.
2024-03-01 | GSE229081 | GEO
Project description:Sparse populations of neurons in the dentate gyrus (DG) of the hippocampus are causally implicated in the encoding of contextual fear memories. However, engram-specific molecular mechanisms underlying memory consolidation remain largely unknown. Here we perform unbiased RNA sequencing of DG engram neurons 24 h after contextual fear conditioning to identify transcriptome changes specific to memory consolidation. DG engram neurons exhibit a highly distinct pattern of gene expression, in which CREB-dependent transcription features prominently (P = 6.2 × 10-13), including Atf3 (P = 2.4 × 10-41), Penk (P = 1.3 × 10-15), and Kcnq3 (P = 3.1 × 10-12). Moreover, we validate the functional relevance of the RNAseq findings by establishing the causal requirement of intact CREB function specifically within the DG engram during memory consolidation, and identify a novel group of CREB target genes involved in the encoding of long-term memory.
| S-EPMC6527697 | biostudies-literature
Project description:Consolidation of long-term memory (LTM) is a complex process requiring synthesis of new mRNAs and proteins. Many studies have characterized the requirement for de novo mRNA and protein synthesis; however, few studies have comprehensively identified genes regulated during LTM consolidation. We show that consolidation of long-term contextual memory in the hippocampus triggers altered expression of numerous genes encompassing many aspects of neuronal function. Like contextual memory formation, this altered gene expression required NMDA receptor activation and was specific for situations in which the animal formed an association between a physical context and a sensory stimulus. Using a bioinformatics approach, we found that regulatory elements for several transcription factors are over-represented in the upstream region of genes regulated during consolidation of LTM. Using a knock-out mouse, we found that c-rel, one of the transcription factors identified in our bioinformatics study, is necessary for hippocampus-dependent long-term memory formation. Keywords: other
2005-03-30 | GSE1782 | GEO
Project description:LncRNAs are involved in critical processes for cell homeostasis and function. However, it remains largely unknown whether and how the transcriptional regulation of long noncoding RNAs results in activity-dependent changes at the synapse and facilitate formation of long-term memories. Here, we report the identification of a novel lncRNA, SLAMR, that becomes enriched in CA1- but not in CA3-hippocampal neurons upon contextual fear conditioning. SLAMR is transported to dendrites via the molecular motor KIF5C and recruited to the synapse in response to stimulation. Loss of function of SLAMR reduced dendritic complexity and impaired activity-dependent changes in spine structural plasticity. Interestingly, the gain of function of SLAMR enhanced dendritic complexity, and spine density through enhanced translation. Analyses of the SLAMR interactome revealed its association with CaMKIIa protein through a 220-nucleotide element and its modulation of CaMKIIa activity. Furthermore, loss-of-function of SLAMR in CA1 selectively impairs consolidation but neither acquisition, recall, nor extinction of fear memory and spatial memory. Together, these results establish a new mechanism for activity dependent changes at the synapse and consolidation of contextual fear memory.
2023-03-13 | MSV000091477 | MassIVE
Project description:Adult rats (male Lister hooded) received a single unsignaled scrambled footshock (0.5 mA for 2 s) 2 min into a 3min exposure to a novel context. One half rats received bilateral microinfusions (1 microlitre/hemisphere) of 2 nmol/microlitre BDNF antisense ODN (BDNFASO, 5’-TCTTCCCCTTTTAATGGT-3’ in PBS, pH 7.4) or BDNF missense ODN (BDNFMSO, 5’ -ATACTTTCTGTTCTTGCC-3’ in PBS, pH 7.4) into the dorsal hippocampus (AP -3.50, relative to bregma), 90 min before contextual fear conditioning (CFC). Infusions were made in awake rats via previously surgically implanted indwelling stainless steel cannula. Rats were housed in the home cages at all times outside the conditioning procedure. Rats were killed by CO2 inhalation 2 hours after CFC. CA1 enriched dorsal hippocampus was immediately dissected on ice before rapid freezing and storage at -80oC. The BDNFASO-infused group represent consolidation-impaired rats.
2015-09-25 | GSE66150 | GEO
Project description:Purpose: we utilized a mouse model that permanently labels neurons activated throughout a specific experience to decipher the interplay between chromatin accessibility, 3D-chromatin architecture and transcriptional changes across different memory phases. Non activated (basal) and activated neurons during memory encoding (early), consolidation (late) and recall (reactivated) were sorted and subjected to nuclear RNA sequencing (nRNA-seq) to determine gene expression, ATAC-seq (Assay for Transposase-Accessible Chromatin using sequencing) to assess chromatin accessibility, chromosome conformation capture (Hi-C) to identify global 3D -genome architecture and promoter capture Hi-C to identify the long range promoter-enhancer interactions. Results: Our differentially expressed gene (DEG) analysis revealed relatively low amount of changes in the early phase, when compared to basal-state neurons (Basal vs. Early). In contrast, neurons from late phase presented higher numbers of DEGs despite there being more similarity in chromatin accessibility at these time points (Early vs. Late; Late vs. Reactivated). Our studies illuminate for the first time the unique transcriptional landscape of reactivated engram cells where we observed up-regulation of genes involved in mRNA transport and local protein translation in synaptic compartments. These changes corresponded to morphological and functional changes in those neurons.
2020-06-23 | GSE152775 | GEO
Project description:The circadian system influences many different biological processes, including memory performance. While the suprachiasmatic nucleus (SCN) functions as the brain’s central pacemaker, downstream “satellite clocks” may also regulate local functions based on the time of day. Within the dorsal hippocampus (DH), for example, local molecular oscillations may contribute to time-of-day effects on memory. Here, we used the hippocampus-dependent Object Location Memory task to determine how memory is regulated across the day/night cycle in mice. First, we systematically determined which phase of memory (acquisition, consolidation, or retrieval) is modulated across the 24h day. We found that mice show better long-term memory performance during the day than at night, an effect that was specifically attributed to diurnal changes in memory consolidation, as neither memory acquisition nor memory retrieval fluctuated across the day/night cycle. Using RNA-sequencing we identified the circadian clock gene Period1 (Per1) as a key mechanism capable of supporting this diurnal fluctuation in memory consolidation, as Per1 oscillates in tandem with memory performance. We then show that local knockdown of Per1 within the DH has no effect on either the circadian rhythm or sleep behavior, although previous work has shown this manipulation impairs memory. Thus, Per1 may independently function within the DH to regulate memory in addition to its known role in regulating the circadian system within the SCN. Per1 may therefore exert local diurnal control over memory consolidation within the DH.
2024-01-12 | GSE222744 | GEO
Project description:FTY720/Fingolimod, an FDA-approved drug for treatment of multiple sclerosis, has beneficial effects in the CNS that are not yet well understood, independent of its effects on immune cell trafficking. Here we show that FTY720 enters the nucleus where it is phosphorylated by sphingosine kinase 2 (SphK2) and nuclear FTY720-P that accumulates there, binds and inhibits class I histone deacetylases (HDACs) enhancing specific histone acetylations. FTY720 is also phosphorylated in mice and accumulates in various brain regions, including hippocampus, inhibits HDACs and enhances histone acetylation and gene expression programs associated with memory and learning leading to improvement of memory impairment independently of its immunosuppressive actions. Our data suggest that sphingosine-1-phosphate and SphK2 play specific roles in memory functions and that FTY720 may be a useful adjuvant therapy to facilitate extinction of aversive memories. Microarrays were used to survey the effect of FTY720 treatment during contextual fear conditioning on hippocampal gene expression. Total RNA was isolated from individual hippocampi of SCID mice 1 hour following fear consolidation testing after the third day of FTY720 or saline treatment. Eight arrays were run in total: 4 FTY720-treated mice and 4 saline-treated control mice.
2014-05-12 | E-GEOD-57015 | biostudies-arrayexpress