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Pyk2 suppresses contextual fear memory in an autophosphorylation-independent manner

ABSTRACT: We demonstrated that Pyk2 is a novel fear memory suppressor molecule and Pyk2 null mice provide a model for understanding fear-related disorders.

ORGANISM(S): Mus musculus

PROVIDER: GSE180598 | GEO | 2022/02/02

REPOSITORIES: GEO

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Pyk2 suppresses contextual fear memory in an autophosphorylation-independent manner

Project description:We demonstrated that Pyk2 is a novel fear memory suppressor molecule and Pyk2 null mice provide a model for understanding fear-related disorders.

2022-02-02 | GSE158606 | GEO

Pyk2 suppresses contextual fear memory in an autophosphorylation-independent manner

Project description:Pyk2 suppresses contextual fear memory in an autophosphorylation-independent manner

| PRJNA665969 | ENA

Pyk2 suppresses contextual fear memory in an autophosphorylation-independent manner

Project description:Pyk2 suppresses contextual fear memory in an autophosphorylation-independent manner

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Pyk2 suppresses contextual fear memory in an autophosphorylation-independent manner.

Project description:Clustered protocadherins (Pcdhs) are a large family of cadherin-like cell adhesion proteins that are central for neurite self-avoidance and neuronal connectivity in the brain. Their downstream nonreceptor tyrosine kinase Pyk2 (proline-rich tyrosine kinase 2, also known as Ptk2b, Cakb, Raftk, Fak2, and Cadtk) is predominantly expressed in the hippocampus. We constructed Pyk2-null mouse lines and found that these mutant mice showed enhancement in contextual fear memory, without significant change in auditory-cued and spatial-referenced learning and memory. In addition, by preparing Y402F mutant mice, we observed that Pyk2 suppressed contextual fear memory in an autophosphorylation-independent manner. Moreover, using high-throughput RNA sequencing, we found that immediate early genes, such as Npas4, cFos, Zif268/Egr1, Arc, and Nr4a1, were enhanced in Pyk2-null mice. We further showed that Pyk2 disruption affected pyramidal neuronal complexity and spine dynamics. Thus, we demonstrated that Pyk2 is a novel fear memory suppressor molecule and Pyk2-null mice provide a model for understanding fear-related disorders. These findings have interesting implications regarding dysregulation of the Pcdh‒Pyk2 axis in neuropsychiatric disorders.

| S-EPMC8782590 | biostudies-literature

Sono-Seq analysis of contextual fear conditioning

Project description:This dataset constitutes the first Sono-Seq study of chromatin accessibility following contextual fear conditioning in the mouse hippocampus.

2017-11-20 | GSE98317 | GEO

RNA-seq analysis of contextual fear conditioning

Project description:This dataset constitutes the first RNA-seq study of gene expression following contextual fear conditioning in the mouse hippocampus.

2015-07-22 | GSE63412 | GEO

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.

2017-01-06 | GSE61529 | GEO

Gene expression in rat hippocampal CA1 during the extinction of contextual fear memory

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

Strain differences in responsiveness to chronic restraint stress affect remote contextual fear memory and blood transcriptomics

Project description:Fear memory regulation is thought to be similar between humans and animals, and the role of stress in altering remote memory is little explored. Since individual variation in stress reactivity exists, should stress alter remote memory, invividuals with differing stress-reactivity would affect it to various degree. We evaluate this question using two strains of rats with differing stress-reactivity. The Fisher 344 (F344) strain is known to have active coping style and represent normal stress-reactivity, while the Wistar–Kyoto (WKY) rat shows passive coping strategies and heightened stress-reactivity. Male animals were exposed contextual fear conditioning (CFC) and four weeks later, chronic restraint stress (CRS) or no stress (NS) was administered for two weeks. Remote memory, immediate stress response to a second CFC, and reinstated fear memory was measured. Both recent and reinstated fear memory were greater in F344s, regardless of the stress status, In contrast, remote memory was attenuated in F344 only, concurring with their increased immediate stress responsive behavior after CRS. To find if this strain-specific response to CRS can be mirrored by transcriptomic changes in the blood, RNA sequencing was carried out. Overlapping differentially expressed genes (DEGs) between NS vs. CRS in the blood of F344 and WKY suggest a convergence of stress-related molecular mechanisms, independent of stress-reactivity. In contrast, DEGs unique to the F344 and the WKY stress responses are divergent in their functionality and networks, beyond that of strain differences in their non-stressed state. These unique DEGs than could be implicated as biomarkers stress-reactivity.

2020-10-01 | GSE148151 | GEO

miRNA and consolidation of cued fear memory

Project description:miRNA profiling was carried out using the miRCURY LNA™ microRNA Array (6th gen - hsa, mmu & rno) miRNA were profiled in amygdala brain tissue obtained from adult mice 30 mins after auditory fear conditioning and expression levels compared to tissue obtained from Home cage controls Adult male mice were fear conditioned using tone-shock pairings and brains were harvested 30 mins later. The brains of Home Cage controls and Fear Conditioned animals (n = 4/group) were then punched to collect amygdala tissue. miRNA were extracted using the Qiagen miRNeasy Kit, and then shipped to Exiqon. Exiqon performed labeling, hybridization and data analysis after use of the miRCURY LNA™ microRNA Array (6th gen - hsa, mmu & rno). https://www.exiqon.com/ls/Documents/Scientific/miRCURY-LNA-microRNA-Array-6th-gen-hsa-mmu-rno-manual.pdf

2014-09-30 | E-GEOD-59072 | biostudies-arrayexpress

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