Mus musculus
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PROVIDER: PRJNA306249 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:HDAC inhibition, dopamine and long-term fear inhibition [mPFC data set]
| PRJNA306250 | ENA
Project description:HDAC inhibition, dopamine and long-term fear inhibition
| PRJNA306245 | ENA
Project description:Background: Extinction-based exposure therapy is used in treating anxiety- and trauma-related disorders, however there is the need to improve its limited efficacy in individuals with impaired fear extinction learning and to facilitate the inadequate protection against return-of-fear phenomena. Methods: Spontaneous recovery and fear renewal tests, assessed persistence and context-independence of treatments rescuing deficient fear extinction in 129S1/SvImJ mice. To reveal neurobiological mechanisms supporting long-lasting extinction rescue, whole-genome expression profiling, qRT-PCR, immunohistochemistry and chromatin immunoprecipitation were used. Results: Persistent and context-independent rescue of deficient fear extinction induced by dietary zinc-restriction was associated with enhanced expression of dopamine-related genes, such as genes encoding the dopamine- D1 (Drd1a) and -D2 (Drd2) receptor in the medial prefrontal cortex (mPFC) and amygdala. Moreover, enhanced histone acetylation was observed in the promoter of the extinction-regulated Drd2 gene in the mPFC, revealing a possibly involved gene regulatory mechanism. While enhancing histone acetylation, via administering the HDAC inhibitor MS275, does not induce successful fear reduction during extinction training, it promoted enduring and context-independent rescue of deficient fear extinction consolidation/retrieval once extinction learning was initiated. This was associated with enhanced neuronal histone acetylation in the mPFC and amygdala. Finally, as a proof of principle, mimicking enhanced dopaminergic signaling by L-dopa treatment rescued deficient fear extinction and co-administration of MS-275 rendered this effect enduring and context-independent. Conclusion: Current data reveal that combining dopaminergic and epigenetic mechanisms is a promising strategy to improve exposure-based behavior therapy in extinction-impaired individuals by initiating the formation of an enduring and context-independent fear inhibitory memory.
2016-12-21 | GSE76108 | GEO
Project description:Background: Extinction-based exposure therapy is used in treating anxiety- and trauma-related disorders, however there is the need to improve its limited efficacy in individuals with impaired fear extinction learning and to facilitate the inadequate protection against return-of-fear phenomena. Methods: Spontaneous recovery and fear renewal tests, assessed persistence and context-independence of treatments rescuing deficient fear extinction in 129S1/SvImJ mice. To reveal neurobiological mechanisms supporting long-lasting extinction rescue, whole-genome expression profiling, qRT-PCR, immunohistochemistry and chromatin immunoprecipitation were used. Results: Persistent and context-independent rescue of deficient fear extinction induced by dietary zinc-restriction was associated with enhanced expression of dopamine-related genes, such as genes encoding the dopamine- D1 (Drd1a) and -D2 (Drd2) receptor in the medial prefrontal cortex (mPFC) and amygdala. Moreover, enhanced histone acetylation was observed in the promoter of the extinction-regulated Drd2 gene in the mPFC, revealing a possibly involved gene regulatory mechanism. While enhancing histone acetylation, via administering the HDAC inhibitor MS275, does not induce successful fear reduction during extinction training, it promoted enduring and context-independent rescue of deficient fear extinction consolidation/retrieval once extinction learning was initiated. This was associated with enhanced neuronal histone acetylation in the mPFC and amygdala. Finally, as a proof of principle, mimicking enhanced dopaminergic signaling by L-dopa treatment rescued deficient fear extinction and co-administration of MS-275 rendered this effect enduring and context-independent. Conclusion: Current data reveal that combining dopaminergic and epigenetic mechanisms is a promising strategy to improve exposure-based behavior therapy in extinction-impaired individuals by initiating the formation of an enduring and context-independent fear inhibitory memory.
2016-12-21 | GSE76103 | GEO
Project description:Fear extinction is an adaptive behavioral process critical for organism’s survival, but deficiency in extinction may lead to PTSD. While the amygdala and its neural circuits are critical for fear extinction, the molecular identity and organizational logic of cell types that lie at the core of these circuits remain unclear. Here we report that mice deficient for amygdala-enriched gastrin-releasing peptide gene (Grp-/-) exhibit enhanced neuronal activity in the basolateral amygdala (BLA) and stronger fear conditioning, as well as deficient extinction in stress-enhanced fear learning (SEFL). rAAV2-retro-based tracing combined with visualization of the GFP knocked in the Grp gene showed that BLA receives several GRPergic conditioned stimulus projections: from the indirect auditory thalamus-to-auditory cortex pathway, medial prefrontal cortex, ventral hippocampus and ventral tegmental area. Transcription of dopamine-related genes was decreased in BLA of Grp-/- mice following SEFL extinction recall, suggesting that the GRP may mediate fear extinction regulation by dopamine.
2021-12-01 | GSE164226 | GEO
Project description:Fear conditioning in rats leads to long term memory (LTM) formation. A central neural substrate for LTM is the basolateral amygdala. We sought the expression changes specific to LTM at 6h following anesthesia with isoflurane (a general anesthetic and an effective amnestic agent), following pain (a component of conditioning), and following conditioning in presence and absence of isoflurane. Keywords = anesthesia, amygdala, LTM, Rampil, Isoflurane, fear, memory Keywords: other
2004-12-31 | GSE1779 | GEO
Project description:Fear conditioning in rats leads to long term memory (LTM) formation. A central neural substrate for LTM is the basolateral amygdala. We sought the expression changes specific to LTM at 6h following anesthesia with isoflurane (a general anesthetic and an effective amnestic agent), following pain (a component of conditioning), and following conditioning in presence and absence of isoflurane.
2007-06-29 | E-GEOD-1779 | biostudies-arrayexpress
Project description:Memory encodes past experiences, thereby enabling future plans. The basolateral amygdala (BLA) is a center of salience networks that underlie emotional experiences and thus plays a key role in long-term fear memory formation. Here we used single-cell transcriptomics to illuminate the cellular and molecular architecture of the role of the basolateral amygdala in long-term memory. We identified transcriptional signatures in subpopulations of neurons and astrocytes that were memory-specific and persisted for weeks. These transcriptional signatures implicate neuropeptide and brain-derived neurotrophic factor (BDNF) signaling, mitogen-activated protein kinase (MAPK) and cAMP response element-binding protein (CREB) activation, ubiquitination pathways, and synaptic connectivity as key components of long-term memory. Strikingly, upon long-term memory formation a neuronal sub-population defined by increased Penk and decreased Tac expression constituted the most prominent component of the BLA’s memory engram.
2023-10-26 | GSE246147 | GEO
Project description:Understanding the mechanisms by which long-term memories are formed and stored in the brain represents a central aim of neuroscience. Prevailing theory suggests that long-term memory encoding involves early plasticity within hippocampal circuits, while reorganization of the neocortex is thought to occur weeks to months later to subserve remote memory storage. Here we report that long-term memory encoding can elicit early transcriptional, structural and functional remodeling of the neocortex. Parallel studies using genome-wide RNA-sequencing, ultrastructural imaging, and whole-cell recording in wild-type mice suggest that contextual fear conditioning initiates a transcriptional program in the medial prefrontal cortex (mPFC) that is accompanied by rapid expansion of the synaptic active zone and postsynaptic density, enhanced dendritic spine plasticity, and increased synaptic efficacy. To address the real-time contribution of the mPFC to long-term memory encoding, we performed temporally precise optogenetic inhibition of excitatory mPFC neurons during contextual fear conditioning. Using this approach, we found that real-time inhibition of the mPFC inhibited activation of the entorhinal-hippocampal circuit and impaired the formation of long-term associative memory. These findings suggest that encoding of long-term episodic memory is associated with early remodeling of neocortical circuits, identify the prefrontal cortex as a critical regulator of encoding-induced hippocampal activation and long-term memory formation, and have important implications for understanding memory processing in healthy and diseased brain states. 4 biological replicates per group were analyzed. The material analyzed was medial prefrontal cortex (mPFC; anterior cingulate cortex subregion) from both brain hemispheres, from which total RNA was extracted.
2014-06-16 | E-GEOD-58510 | biostudies-arrayexpress
Project description:Neuroimmune interactions—signals transmitted between immune and brain cells—regulate many aspects of tissue physiology including responses to psychological stress, which can predispose individuals to develop neuropsychiatric diseases. Still, the interactions between hematopoietic and brain-resident cells that influence complex behaviors are poorly understood. Here, we used a combination of genomic and behavioral screens to demonstrate that astrocytes in the amygdala limit stress-induced fear behavior through EGFR. Mechanistically, amygdala astrocyte EGFR expression inhibits a stress-induced pro-inflammatory signal transduction cascade that facilitates neuro-glial cross-talk and stress-induced fear behavior through the orphan nuclear receptor NR2F2 in amygdala neurons. We uncovered that, in turn, decreased EGFR signaling and fear behavior were associated with meningeal monocyte recruitment during chronic stress. This set of neuroimmune interactions was therapeutically targetable by psychedelic administration, which reversed monocyte accumulation in the brain meninges along with fear behavior. Together with validation in clinical samples, these data suggest that psychedelics can be used to target neuroimmune interactions relevant to neuropsychiatric disorders and potentially other inflammatory diseases.
2025-03-03 | GSE281355 | GEO