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Reactivation of memory-encoding dentate gyrus neurons during memory consolidation is associated with subregion-specific, learning- and sleep-mediated biosynthetic changes.

ABSTRACT: This superseries contain NanoString GeoMx spatial profiling datasets that measured RNA and protein expression levels from ROIs of mice that received fear-conditioning and/or sleep deprivation. ROIs were collected from both hemispheres of the brain, including 5 different subregions of the hippocampus (CA1, CA3, DG-superior blade, DG-inferior blade, and DG-hilus).

ORGANISM(S): Mus musculus blank sample

PROVIDER: GSE229082 | GEO | 2024/02/27

REPOSITORIES: GEO

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Reactivation of memory-encoding dentate gyrus neurons during memory consolidation is associated with subregion-specific, learning- and sleep-mediated biosynthetic changes [spatial protein expression level]

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

2024-03-01 | GSE229080 | GEO

Sleep-dependent engram reactivation during hippocampal memory consolidation associated with subregion-specific biosynthetic changes.

Project description:Post-learning sleep is essential for hippocampal memory processing, including contextual fear memory consolidation. We labeled context-encoding engram neurons in the hippocampal dentate gyrus (DG) and assessed reactivation of these neurons after fear learning. Post-learning sleep deprivation (SD) selectively disrupted reactivation of inferior blade DG engram neurons, linked to SD-induced suppression of neuronal activity in the inferior, but not superior DG blade. Subregion-specific spatial profiling of transcripts revealed that transcriptomic responses to SD differed greatly between hippocampal CA1, CA3, and DG inferior blade, superior blade, and hilus. Activity-driven transcripts, and those associated with cytoskeletal remodeling, were selectively suppressed in the inferior blade. Critically, learning-driven transcriptomic changes differed dramatically between the DG blades and were absent from all other regions. Together, these data suggest that the DG is critical for sleep-dependent memory consolidation, and that the effects of sleep loss on the hippocampus are highly subregion-specific.

| S-EPMC10957462 | biostudies-literature

Engram-specific transcriptome profiling of contextual memory consolidation

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

Spatial transcriptomics of in vivo invasive trancheobronchitis biopsies obtained from patients with influenza-associated pulmonary aspergillosis or COVID-19-associated pulmonary aspergillosis

Project description:To assess whether transcriptional differences exist in the epithelial tissue and the inflammatory infiltrate of invasive Aspergillus tracheobronchitis in patients with severe influenza or severe COVID-19, we performed GeoMx spatial transcriptomics on four biopsy samples in total: two of patients with influenza-associated pulmonary aspergillosis (IAPA) and two of patients with COVID-19-associated pulmonary aspergillosis (CAPA). Several regions of interest (ROIs) were delineated in each biopsy sample, and transcriptomic data was derived of each of these ROIs using GeoMx with a whole transcriptome atlas with SARS-CoV-2 spike-in.

2022-08-24 | GSE198096 | GEO

Hippocampal Subregion Transcriptomic Profiles Associated with Age-Related Changes in Spatial Pattern Separation

Project description:Previous studies of age-related transcriptional changes indicate that cognitive impairments are associated with differentially expressed genes DEGs linked to defined neural systems; however, studies that examine multiple regions of the hippocampus fail to find major links between behavior and transcription in the dentate gyrus DG. The DG is implicated in pattern separation PS and exhibits multiple age-related changes that may affect PS performance. We hypothesize that an age-related decline in PS performance is associated with distinct changes in transcriptional profile, most strongly within the DG compared to other hippocampal subregions. We used a water maze beacon discrimination task to characterize PS in young 5 mo and middle-age 12 mo male F344 rats, followed by a spatial reference memory test. Middle-age rats showed consistent deficits in discriminating two identical beacons compared to young. Reference memory was not different between these two age groups. Interestingly, with increasing spatial overlap between the cues, older animals appeared to compensate for impaired PS performance though greater reliance on spatial reference memory. mRNA sequencing of hippocampal subregions DG, CA1, and CA3 indicated that the DG of middle-age rats expressed more genes correlated with PS performance. In contrast, reliance on a spatial reference memory was associated with differential expression of genes in regions CA1 and CA3. These results indicate that the beacon task is sensitive to PS impairment as early as middle-age, and distinct gene profiles are observed in neural circuits that underlie different strategies used to solve the task.

2020-05-22 | GSE140420 | GEO

Reactivation of memory-encoding dentate gyrus neurons during memory consolidation is associated with subregion-specific, learning- and sleep-mediated biosynthetic changes.

Project description:Reactivation of memory-encoding dentate gyrus neurons during memory consolidation is associated with subregion-specific, learning- and sleep-mediated biosynthetic changes.

| PRJNA952689 | ENA

GeoMx Cancer Transcriptome Atlas (CTA) mRNA assay on 191 ROIs from a NSCLC tumor.

Project description:GeoMx Cancer Transcriptome Atlas (CTA) mRNA assay on 191 ROIs from a NSCLC tumor.

| PRJNA731400 | ENA

TNF-α released by melanoma liver metastasis activates AKT and NFKβ1 pathways to promote collagen type I secretion by hepatocytes

Project description:A total of four human melanoma liver metastasis (MLiM) formalin-fixed paraffin-embedded (FFPE) sections were analyzed using Nanostring GeoMx digital spatial profiling (NGDSP). The FFPE tissues were obtained from patients who underwent surgery and were pathological diagnosed with MLiM. Patients who had received any preoperative therapy were excluded. In each region of interest (ROI), two areas of interest (AOI)s were defined by HepPar1+ (hepatocytes); HMB45+ (melanoma cells) staining. A total of 43 AOIs were carefully reviewed for segments with sequencing saturation < 25%, nuclei fewer than 80, negative probe counts <3, or a surface area of <12,000 squared microns. Background correction and scaling were performed using geometric means and normalization was performed using Q3 averages of housekeeping genes. Genes with expression levels at or lower than limit of quantification (LOQ) in at least 5% of segments were filtered out. A total of 1,811 genes passed quality control and were analyzed. A total of seven ROIs with tumor margin (TM) and 13 ROIs with tumor center (TC) were selected, respectively. TM was defined as the areas on the border of malignant tumor cells close to normal tissue based on pathological features. TC was defined as central tumor tissue further inside from TM. In addition, 14 ROIs were selected at ANH. The ANH areas were defined as an area within 1,200 µm from the TM. Furthermore, nine ROIs were selected at the DNH areas. DNH was defined as an area at least 6 mm away from TM. Differential expressed genes (DEGs, Log2 fold-change >1.5, <-1.5, p < 0.05) were calculated on AOIs selected from MLiM comparing TC vs. TM; ANH vs. DNH; and ANH vs. Melanoma cells (TC+TM).

2024-11-13 | GSE255328 | GEO

FoxO6 regulates memory consolidation and synaptic function.

Project description:We used microarrays to assess gene expression differences in the hippocampus between FoxO6 mutant and wild-type siblings before (basal) or after novel object learning. The cohort of basal mice were housed individually for at least 3 days prior to tissue harvesting. The mice used to collect hippocampal samples after the object learning task were handled daily in the procedure room, prior to the object learning task. 24 hours before the object learning task, each mouse was individually habituated to the empty novel object arena for 10 min. On the days of the novel object learning task and the empty arena habituation, the mice were transferred to the procedure room and acclimatized for 60 min. For the novel object learning task, the mice were allowed to explore two identical and novel objects for 10 min in a 70 x 70 x 70 cm black plastic arena with a white PVC vinyl material on the base. After the object exploration, mice were transferred to an empty cage, and were euthanized after 60 min. The brains were dissected and incubated in ice-cold RNAlater (Ambion) for 24 hours at 4M-BM-:C. The brains were then rapidly frozen in O.C.T. Tissue-Tek (Sakura) at -80M-BM-:C. Coronal brain sections (300 M-BM-5m) were made using a microtome (Microm), the hippocampus was finely dissected and collected into M-bM-^@M-^XRNA lysis bufferM-bM-^@M-^Y (Ambion), and homogenized for 30 sec using a rotar-stat homogenizer. Total RNA was extracted using the RNAqueous column (Ambion) following the manufacturerM-bM-^@M-^Ys protocol.

2012-11-08 | E-GEOD-42097 | biostudies-arrayexpress

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