Project description:naïve and trained rats 24 hours after exposure to the contextual fear conditioning paradigm. Biological replicates: 4 naïve and 4 trained animals, independently conditioned and tissues were independently isolated. One replicate per array.
Project description:naïve and trained rats 24 hours after exposure to the contextual fear conditioning paradigm. Biological replicates: 3 independent pools of 3 animals each, 6 naïve and 6 trained animals, independently conditioned and tissues were independently isolated. One replicate per array.
Project description:Extinction learning refers to the phenomenon that a previously learned response to an environmental stimulus, for example the expression of an aversive behavior upon exposure to a specific context, is reduced when the stimulus is repeatedly presented in the absence of a previously paired aversive event. Extinction of fear memories has been implicated with the treatment of anxiety disease but the molecular processes that underlie fear extinctionare only beginning to emerge. Here we show that fear extinction initiates up-regulation of hippocampal insulin-growth factor 2 (Igf2) and down-regulation of insulin-growth factor binding protein 7 (Igfbp7). In line with this observation we demonstrate that IGF2 facilitates fear extinction, while IGFBP7 impairs fear extinction in an IGF2-dependent manner. Furthermore, we identify one cellular substrate of altered IGF2-signaling during fear extinction. To this end we show that fear extinction-induced IGF2/IGFBP7-signaling promotes the survival of 17-19 day-old newborn hippocampal neurons. In conclusion, our data suggests that therapeutic strategies that enhance IGF2-signaling and adult neurogenesis might be suitable to treat disease linked to excessive fear memory. We employed mice to investigate fear extinction in the hippocampus-dependent contextual fear conditioning paradigm. To this end, male C57BL/6J mice were exposed to the fear conditioning box (context) followed by an electric foot-shock which elicits the acquisition of conditioned contextual fear. For extinction training animals were repeatedly reexposed to the conditioned context on consecutive days (24h interval) without receiving the footshockagain (extinction trial, E). This procedure eventually results in the decline of the aversive freezing behavior. Mice that were exposed to the conditioning context without receiving fear conditioning training served as control groups. To gain a better understanding of the molecular processes underlying fear extinction we performed a genome-wide analysis of the hippocampal transcriptome during fear extinction. In the employed paradigm fear extinction is a gradual process. To capture the longitudinal course of fear extinction we decided to perform hippocampal microarray analysis at two time points: (1) After the first extinction trial (E1) when animals display high levels of aversive freezing behavior and (2) at the extinction trial on which the freezing behavior was significantly reduced when compared to E1. This extinction trial, in the case of this experiment E5, we termed “extinction trial low freezing” (ELF). Mice that were exposed to the conditioning context without receiving fear conditioning training served as control groups (3). For all three groups we hybridized 5 samples (biological replicates).
Project description:Quantitative proteomic analysis was used to identify the proteins associated with a formation of fear memory in mice. The proteins from the hippocampal region were isolated from three groups of trained aminals representing aquisition, consolidation and retrieval of a contextual fear conditioning. The samples were digested by trypsin, analyzed by LC-MSMS followed by protein identification and label-free quantitation using MaxQuant 1.3.0.5. Each group consisted of three individuals and each sample was processed in two technical replicates.
Project description:This experiment seeks to ascertain the transcriptional changes in the adult mouse hippocampus (CA1 subregion) that occur following viral knockdown of the histone variant H2A.Z. We are especially interested in understanding the role of this histone variant in memory formation and memory maintenance in the adult central nervous system. This experiment includes 3 groups, each with 3 biological replicates. Samples S108, S109, and S110 are from controls infected with an AAV expressing a scrambled shRNA control. Samples A100, A101, A102, A104, A106, and A107 were infected with an AAV expressing an shRNA against H2A.Z. Samples A100, A101, and A102 were naive animals, whereas samples A104, A106, and A107 were trained in contextual fear conditioning.
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.
Project description:Mice with the two calcium-stmulated adenylyl cyclase isoforms (AC1 and AC8; DKO mice) knocked-out show conditioned fear memory deficits. We assessed gene expression changes at baseline and several time points after conditioned fear learning to assess transcriptional changes at different stages of learning. Transcriptional changes were assessed in the amydgdala and hippocampus of DKO and wild-type mice. Mice either received no treatment (baseline) or were subjected to conditioned fear training (one 0.7mA x 2 sec shock). Amygdala and hippocampal tissue from wild-type and DKO (AC1 and AC8 KO) mice was used. Samples were extracted at baseline (-5 min before conditioned fear training), 0 hr, 1 hr, or 48 hr after a 5 min conditioned fear training trial, or at 1 wk after a 5 min conditioned fear testing trial. RNA samples from 5-10 mice were pooled per array with one array per genotype/brain region/time point for a total of 20 arrays. mRNA was reverese transcribed, labeled and hybridized to Affymetric Mouse Gene ST 1.0 Arrays.
Project description:Using Illumina MouseWG-6v2 microarrays, we investigated the gene transcription changes in microglia and peripheral monocytes after contextual fear conditioning of C57BL/6J mice. Mice were trained with or without a single minimized footshock stimulation (0-s or 2-s, 0.4 mA) and re-exposed to the training context without footshock for three different durations 24 h later: 0 min (FS0), 3 min (FS3), or 30 min (FS30). Whole brain microglia and peripheral monocytes were prepared 24 h after re-exposure using a neural tissue dissociation kit, including non-footshock controls for two re-exposure durations (Con3 and Con30). The data can be valuable for researchers interested in glial cells and neurotransmission studies and are related to the research article “Contextual fear conditioning regulates synapse-related gene transcription in mouse microglia”.