Characterization of a novel gene-environment-based animal model to study resilience and susceptibility to PTSD and co-morbid depression DOI Creative Commons
Lia P. Iglesias, Arthur Alves Coelho, Nicole Rodrigues da Silva

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: Sept. 16, 2022

ABSTRACT BACKGROUND Post-traumatic stress disorder (PTSD) and co-morbid depression are frequently associated with severe symptoms, poor response to treatment worse prognosis. Due the absence of a suitable animal model, little is known about biological basis comorbidity, severely limiting discovery new more effective options. The Flinders Sensitive Line rats (FSL) well-validated, selectively bred model depression. However, several its features, such as cognitive deficits altered hypothalamic-pituitary-adrenal (HPA) axis response, also match symptomatic clusters PTSD. In parallel, resistant counterpart, Resistant (FRL), extensively used simple control. Still, performance compared original strain, Sprague Dawley (SD), from which FSL/FRL was originally derived. AIMS Characterizing behavioural mechanisms involved in FSL, FRL SD fear-memory paradigms. METHODS animals were submitted tests assessing hippocampal-dependent fear-related memory. Subsequently, plasticity factors endocrine responses analysed elucidate molecular for observed alterations. RESULTS We found that presented intact recognition memory innate fear but could not properly display conditioned Conditioned Fear Conditioning (CFC) paradigm. FSL animals, despite Novel Object Recognition task (NOR), showed similar levels SD, impairments extinction learning, feature highly related alterations accompanied by plasma corticosterone hippocampal expression glucocorticoid receptor FKBP51. CONCLUSION For first time, we demonstrate an resilience vulnerability PTSD results suggest endophenotypes may be based on aberrant hippocampus.

Language: Английский

Emotional Value of Fear Memory and the Role of the Ventral Hippocampus in Systems Consolidation DOI

Mirelle Araujo Casagrande,

Rossana Rosa Porto, Josué Haubrich

et al.

Neuroscience, Journal Year: 2023, Volume and Issue: 535, P. 184 - 193

Published: Nov. 8, 2023

Language: Английский

Citations

2

Manipulation of neuronal activity in the entorhinal-hippocampal circuit affects intraneuronal amyloid-β levels DOI Open Access
Christiana Bjorkli,

Nora Cecilie Ebbesen,

Joshua B. Julian

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: July 5, 2022

Abstract One of the neuropathological hallmarks Alzheimer’s disease (AD) is accumulation amyloid-β (Aβ) plaques, which preceded by intraneuronal build-up toxic, aggregated Aβ during progression. plaques are first deposited in neocortex before appearing medial temporal lobe, and tau pathology with subsequent neurodegeneration latter anatomical region causes early memory impairments patients. Current research suggests that may begin superficial layers lateral entorhinal cortex (LEC). To examine whether manipulation neuronal activity LEC layer II neurons affected levels downstream perforant path terminals hippocampus (HPC), we used a chemogenetic approach to selectively chronically silence young aged 3xTg AD mice monitored its effect on HPC. Chronic silencing led reduced projection HPC, compared controls. Early HPC correlated LEC, subiculum being earliest subregion involved, our findings give evidence neuropathology originating select populations.

Language: Английский

Citations

3

Fear Memory in Experimental Models of Parkinson’s Disease DOI
Elena Timofeeva, Н. И. Дубровина, Maria A. Tikhonova

et al.

Advances in Gerontology, Journal Year: 2024, Volume and Issue: 14(1), P. 1 - 13

Published: March 1, 2024

Language: Английский

Citations

0

Spatially Resolved Transcriptomic Signatures of Hippocampal Subregions andArc-Expressing Ensembles in Active Place Avoidance Memory DOI Creative Commons

Isaac Vingan,

Shwetha Phatarpekar,

Victoria Sook Keng Tung

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

ABSTRACT The rodent hippocampus is a spatially organized neuronal network that supports the formation of spatial and episodic memories. We conducted bulk RNA sequencing transcriptomics experiments to measure gene expression changes in dorsal following recall active place avoidance (APA) memory. Through sequencing, we examined memory across functionally distinct subregions hippocampus. found induced differentially expressed genes (DEGs) CA1 CA3 hippocampal were enriched with involved synaptic transmission plasticity, while DEGs dentate gyrus (DG) energy balance ribosomal function. transcriptomics, an array spots encompassing putative memory-associated ensembles marked by IEGs Arc , Egr1 c-Jun . Within samples from both trained untrained mice, subpopulations transcriptomic these transcriptomically one another. detected between + -spots exclusively mouse several memory-related ontology terms, including “regulation plasticity” “memory.” Our results suggest APA supported regionalized profiles separating DG, transcriptionally IEG expressing spots, biological processes related plasticity as defining difference -spatial spots.

Language: Английский

Citations

0

Parvalbumin-expressing basal forebrain neurons mediate learning from negative experience DOI Creative Commons

Panna Hegedüs,

B. Király, Dániel Schlingloff

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: June 7, 2024

Abstract Parvalbumin (PV)-expressing GABAergic neurons of the basal forebrain (BFPVNs) were proposed to serve as a rapid and transient arousal system, yet their exact role in awake behaviors remains unclear. We performed bulk calcium measurements electrophysiology with optogenetic tagging from horizontal limb diagonal band Broca (HDB) while male mice performing an associative learning task. BFPVNs responded distinctive, phasic activation punishment, but showed slower delayed responses reward outcome-predicting stimuli. Optogenetic inhibition during punishment impaired formation cue-outcome associations, suggesting causal learning. received strong inputs hypothalamus, septal complex median raphe region, they synapsed on diverse cell types key limbic structures, where broadcasted information about aversive propose that arousing effect is recruited by stimuli crucial functions.

Language: Английский

Citations

0

Neurobiological mechanisms of social recognition memory DOI
Gaeun Park, Yong‐Seok Lee

Elsevier eBooks, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Language: Английский

Citations

0

Mapping functional traces of opioid memories in the rat brain DOI Creative Commons

Joana Gomes-Ribeiro,

João Martins, José Sereno

et al.

Brain Communications, Journal Year: 2024, Volume and Issue: 6(5)

Published: Jan. 1, 2024

Abstract Addiction to psychoactive substances is a maladaptive learned behaviour. Contexts surrounding drug use integrate this aberrant mnemonic process and hold strong relapse-triggering ability. Here, we asked where context salience might be concurrently represented in the brain during retrieval of drug–context paired associations. For this, developed morphine-conditioned place preference protocol that allows contextual stimuli presentation inside magnetic resonance imaging scanner investigated differences activity connectivity at recall. We found context-specific responses stimulus onset multiple regions, namely, limbic, sensory striatal. Differences functional interconnectivity were among amygdala, lateral habenula, septum. also alterations resting-state increased centrality septum proposed limbic network, as well habenula hippocampal ‘cornu ammonis’ 1 region, after associative drug–context. Finally, pre- conditioned amygdala was predictive inter-individual score differences. Overall, our findings show saline-paired contexts establish distinct memory traces overlapping microcircuits intrinsic septum, likely underlies individual learning opioid exposure. have identified maps acquisition drug-related may support ability opioid-associated cues. These clarify sensitivity vulnerability seen addiction opioids humans.

Language: Английский

Citations

0

Connectivity of the neuronal network for contextual fear memory is disrupted in a mouse model of third-trimester binge-like ethanol exposure DOI Creative Commons
Mitchell D. Morningstar, Katalina M Lopez,

Stefanie S. Mayfield

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 19, 2024

Background: In rodents, third-trimester equivalent alcohol exposure (TTAE) produces significant deficits in hippocampal-dependent memory processes such as contextual fear conditioning (CFC). The present study sought to characterize changes both behavior and Fos+ neurons following CFC ethanol (EtOH)-treated versus saline-treated mice using TRAP2:Ai14 that permanently label a tamoxifen injection. We hypothesized TTAE would produce long-lasting disruptions the networks engaged with particular emphasis on limbic system. Methods: On postnatal day 7, received either two injections of saline or 2.5 g/kg EtOH spaced 2 hours apart. were left undisturbed until they reached adulthood, at which point underwent CFC. After context 2, Brain tissue was harvested. Slides automatically imaged Zeiss AxioScanner. Manual counts priori regions interest conducted. Automated performed whole brain QUINT 2D stitching pipeline. Last, novel network analyses applied identify future interest. Results: reduced recall neural density increased CA1 CA3. anteroventral (AV) anterodorsal thalamus. system showed hyperconnectivity male AV shifted affinity towards hippocampal subregions. subparafascicular area basomedial amygdalar nucleus implicated important mediators. Discussion: These results suggest is mediated by disrupted TTAE. Given increase CA3 activity, potential hypothesis causes encoding 1 conditioning. Future studies will aim determine whether this disruption specifically affects retrieval memories.

Language: Английский

Citations

0

Spatially resolved transcriptomic signatures of hippocampal subregions and Arc-expressing ensembles in active place avoidance memory DOI Creative Commons

Isaac Vingan,

Shwetha Phatarpekar,

Victoria Sook Keng Tung

et al.

Frontiers in Molecular Neuroscience, Journal Year: 2024, Volume and Issue: 17

Published: Oct. 31, 2024

The rodent hippocampus is a spatially organized neuronal network that supports the formation of spatial and episodic memories. We conducted bulk RNA sequencing transcriptomics experiments to measure gene expression changes in dorsal following recall active place avoidance (APA) memory. Through sequencing, we examined memory across functionally distinct subregions hippocampus. found induced differentially expressed genes (DEGs) CA1 CA3 hippocampal were enriched with involved synaptic transmission plasticity, while DEGs dentate gyrus (DG) energy balance ribosomal function. transcriptomics, an array spots encompassing putative memory-associated ensembles marked by IEGs

Language: Английский

Citations

0

Automated cell detection for immediate early gene-expressing neurons using inhomogeneous background subtraction in fluorescent images DOI Open Access
Hisayuki Osanai,

M Arai,

Takashi Kitamura

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 8, 2024

Abstract Although many methods for automated fluorescent-labeled cell detection have been proposed, not all of them assume a highly inhomogeneous background arising from complex biological structures. Here, we propose an algorithm that accounts and subtracts the by avoiding high-intensity pixels in blur filtering calculation. Cells were detected intensity thresholding background-subtracted image, algorithm’s performance was tested on NeuN- c-Fos-stained images mouse prefrontal cortex hippocampal dentate gyrus. In addition, applications c-Fos positive counting quantification expression level double-labeled cells demonstrated. Our method after assumption (ADABA) offers advantage high-throughput unbiased analysis regions with structures produce background. Highlights - We proposed to subtract pattern. (79/85) automatically image. (71/85) The results corresponded manual detection. (73/85) Detection IEG overlapping neural marker (85/85)

Language: Английский

Citations

0