Gene expression in rat hippocampal CA1 associated with contextual fear memory formation and recall
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE66153 | GEO | 2015/09/25
SECONDARY ACCESSION(S): PRJNA275970
REPOSITORIES: GEO
Similar Datasets
Project description:Gene expression in rat hippocampal CA1 associated with contextual fear memory formation and recall
| PRJNA275970 | ENA
Project description:Adult rats (male Lister hooded) were pre-exposed for 3 d for 10 min /d (24 hr interval) to two different novel contexts. On day 4 rats received a single unsignaled scrambled footshock (0.5 mA for 2 s) 2 min into a 3min exposure to one of the two contexts. Rats were either returned to the CS conditioned context (CS+, EXT group) or to the other (CS-, NOR group) context for 10 min, 48h after contextual fear conditioning. Rats were housed in the home cages at all times outside the conditioning and re-exposure components. The novel context chosen to be the conditioned context was counterbalanced across the experimental groups. Rats were killed by CO2 inhalation 2 hours after CS- or CS+ exposure. CA1-enriched dorsal hippocampus was immediately dissected on ice before rapid freezing and storage at -80oC. The CS+ group represents rats that underwent extinction of contextual fear memory.
2015-09-25 | GSE66151 | GEO
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:Histone modifications have been implicated in learning and memory. Our previous transcriptome data showed that expression of sirtuins 6 (SIRT6), a member of Histone deacetylases (HDACs) family in the hippocampal cornu ammonis 1 (CA1) was decreased after contextual fear conditioning. However, the role of SIRT6 in the formation of memory is still elusive. In the present study, we found that contextual fear conditioning inhibited translational expression of SIRT6 in the CA1. Microinfusion of lentiviral vector-expressing SIRT6 into theCA1 region selectively enhanced the expression of SIRT6 and impaired the formation of long-term contextual fear memory without affecting short-term fear memory. The overexpression of SIRT6 in the CA1 had no effect on anxiety-like behaviors or locomotor activity. Also, we also found that SIRT6 overexpression significantly inhibited the expression of insulin-like factor 2 (IGF2) and amounts of proteins and/or phosphoproteins (e.g. Akt, pAkt, mTOR and p-mTOR) related to the IGF2 signal pathway in the CA1. These results demonstrate that the overexpression of SIRT6 in the CA1 impaired the formation of long-term fear memory, and SIRT6 in the CA1 may negatively modulate the formation of contextual fear memory via inhibiting the IGF signaling pathway.
| S-EPMC4702175 | biostudies-literature
Project description:We investigated the distinctiveness of gene regulatory networks in CA1 associated with the extinction of contextual fear memory (CFM) after recall using Affymetrix GeneChip Rat Genome 230 2.0 Arrays. These data were compared to previously published retrieval and reconsolidation-attributed, and consolidation datasets. A stringent dual normalization and pareto-scaled orthogonal partial least-square discriminant multivariate analysis together with a jack-knifing-based cross-validation approach was used on all datasets to reduce false positives. Consolidation, retrieval and extinction were correlated with distinct patterns of gene expression 2 hours later. Extinction-related gene expression was most distinct from the profile accompanying consolidation. A highly specific feature was the discrete regulation of neuroimmunological gene expression associated with retrieval and extinction. Immunity-associated genes of the tyrosine kinase receptor TGFβ and PDGF, and TNF families' characterized extinction. Cytokines and proinflammatory interleukins of the IL-1 and IL-6 families were enriched with the no-extinction retrieval condition. We used comparative genomics to predict transcription factor binding sites in proximal promoter regions of the retrieval-regulated genes. Retrieval that does not lead to extinction was associated with NF-κB-mediated gene expression. We confirmed differential NF-κBp65 expression, and activity in all of a representative sample of our candidate genes in the no-extinction condition. The differential regulation of cytokine networks after the acquisition and retrieval of CFM identifies the important contribution that neuroimmune signalling plays in normal hippocampal function. Further, targeting cytokine signalling upon retrieval offers a therapeutic strategy to promote extinction mechanisms in human disorders characterised by dysregulation of associative memory.
| S-EPMC4880201 | biostudies-literature
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. 48 hours later, rats were reexopsed to the condition context for 2 min (TEST). One half rats received bilateral microinfusions (1 microlitre/hemisphere) of 2 nmol/microlitre Zif268 antisense ODN (ZIFASO, 5’- GGTAGTTGTCCATGGTGG-3’in PBS, pH 7.4) or Zif268 missense ODN (ZIFMSO, 5’ -GTGTTCGGTAGGGTGTCA-3’in PBS, pH 7.4) into the dorsal hippocampus (AP -3.50, relative to bregma), 90 min before TEST. 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 and TEST procedures. Rats were killed by CO2 inhalation 2 hours after TEST. CA1-enriched dorsal hippocampus was immediately dissected on ice before rapid freezing and storage at -80oC. The ZIFSO-infused group potentially represents reconsolidation-impaired rats.
2015-09-25 | GSE66152 | GEO
Project description:Hippocampus-dependent spatial and aversive memory processes entail Ca2+ signals generated by ryanodine receptor (RyR) Ca2+ channels residing in the endoplasmic reticulum membrane. Rodents exposed to different spatial memory tasks exhibit significant hippocampal RyR upregulation. Contextual fear conditioning generates robust hippocampal memories through an associative learning process, but the effects of contextual fear memory acquisition, consolidation, or extinction on hippocampal RyR protein levels remain unreported. Accordingly, here we investigated if exposure of male rats to contextual fear protocols, or subsequent exposure to memory destabilization protocols, modified the hippocampal content of type-2 RyR (RyR2) channels, the predominant hippocampal RyR isoforms that hold key roles in synaptic plasticity and spatial memory processes. We found that contextual memory retention caused a transient increase in hippocampal RyR2 protein levels, determined 5?h after exposure to the conditioning protocol; this increase vanished 29?h after training. Context reexposure 24?h after training, for 3, 15, or 30?min without the aversive stimulus, decreased fear memory and increased RyR2 protein levels, determined 5?h after reexposure. We propose that both fear consolidation and extinction memories induce RyR2 protein upregulation in order to generate the intracellular Ca2+ signals required for these distinct memory processes.
| S-EPMC6079367 | biostudies-literature
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).
2023-08-07 | GSE214838 | GEO
Project description:Butyrylcholinesterase (BChE) efficiently hydrolyzes acetylcholine (ACh) at high concentrations when acetylcholinesterase (AChE) is substrate-inhibited. Recent studies have shown that BChE also has a function that is independent of ACh, but it has not been fully explored. Low BChE expression is accompanied with higher stress-induced aggression and ghrelin levels in stress models, and BChE knockout mice exhibit cognitive and memory impairments. However, the role of BChE in posttraumatic stress disorder (PTSD) remains unclear. In the present study, we investigated the role of BChE in contextual fear memory and its regulatory effect on the expression of factors related to the glutamate (Glu)-glutamine (Gln) cycle via knockdown studies. We used AAVs and lentiviruses to knockdown BChE expression in the mouse hippocampal CA1 region and C8D1A astrocytes. Our behavioral data from those mice injected with AAV-shBChE in the hippocampal CA1 region showed strengthened fear memory and increased dendritic spine density. Elevated Glu levels and glutamine synthetase (GS) enzyme activity were detected in contextual fear conditioned-BChE knockdown animals and astrocytes. We observed that an AAV-shBChE induced lowering of BChE expression in the hippocampus CA1 region enhanced contextual fear memory expression and promoted the astrocytic Glu-Gln cycle but did not elevate ACh-hydrolyzing activity. This study provides new insight into the regulatory role of BChE in cognition and suggests potential target for stress-related psychiatric disorder such as PTSD where patients experience fear after exposure to severe life-threatening traumatic events.
| S-EPMC7518375 | biostudies-literature
Project description:Clustered protocadherins (Pcdhs), a large group of adhesion molecules, are important for axonal projections and dendritic spread, but little is known about how they influence neuronal activity. The Pcdhβ cluster is strongly expressed in the hippocampus, and in vivo Ca2+ imaging in Pcdhβ-deficient mice revealed altered activity of neuronal ensembles but not of individual cells in this region in freely moving animals. Specifically, Pcdhβ deficiency increased the number of large-size neuronal ensembles and the proportion of cells shared between ensembles. Furthermore, Pcdhβ-deficient mice exhibited reduced repetitive neuronal population activity during exploration of a novel context and were less able to discriminate contexts in a contextual fear conditioning paradigm. These results suggest that one function of Pcdhβs is to modulate neural ensemble activity in the hippocampus to promote context discrimination.
| S-EPMC6971911 | biostudies-literature