Neurobiology of Stress最新文献

{"title":"Virtual stress testing: Analyzing endocrine, metabolic, cardiovascular, and psychological responses to the TSST-VR","authors":"Eva Fellinger ,&nbsp;Tom Brandt ,&nbsp;Andrea Schittenhelm ,&nbsp;Eric Quarg ,&nbsp;Matthias Pröll ,&nbsp;Gregor Domes ,&nbsp;Annette Schmidt","doi":"10.1016/j.ynstr.2025.100760","DOIUrl":"10.1016/j.ynstr.2025.100760","url":null,"abstract":"<div><h3>Background</h3><div>The Trier Social Stress Test (TSST) is a widely used tool for inducing and measuring stress responses in a controlled environment. In this study, we aimed to explore the effectiveness of a virtual TSST (TSST-VR) in eliciting stress responses across multiple physiological and psychological markers.</div></div><div><h3>Methods</h3><div>A sample of 24 participants underwent the TSST-VR, during which salivary cortisol, alpha-amylase (AA), blood glucose levels, heart rate (HR), root mean square of successive differences (RMSSD) as a measure of heart rate variability (HRV), and subjective stress ratings (NRS) were collected at multiple time points.</div></div><div><h3>Results</h3><div>In a baseline-to-peak analysis, significant increases were observed in HR (M_Diff = 13.04, 95 %-CI [8.19–17.90], p &lt; .001), RMSSD (M_Diff = 17.75, 95 %-CI [3.28–32.22], p &lt; .001), AA (p &lt; .001, r = 1.07), and NRS (p &lt; .001, r = 1.31) measures following the TSST-VR. While no significant changes in cortisol levels were found in the baseline-to-peak analysis across all participants, a secondary cluster analysis identified distinct cortisol responders (baseline-to-peak rise &gt;1.5 mmol/l). Within this group, high cortisol responders (HCR) showed significantly higher cortisol (Wald χ²(7) = 118.03, p &lt; .001), HR (Wald χ²(8) = 17.91, p = .022), and AA levels (Wald χ²(7) = 17.13, p = .017) compared to low cortisol responders (LCR). Area-under-the-curve analysis further confirmed a more robust cortisol stress response in HCR.</div></div><div><h3>Conclusion</h3><div>These findings suggest that the TSST-VR can effectively induce measurable stress responses and may provide insights into individual differences in physiological and metabolic stress reactions. The study highlights the potential of virtual stress paradigms in stress research and underscores the advantages of a virtual setting in terms of standardization and economic considerations.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"39 ","pages":"Article 100760"},"PeriodicalIF":3.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145057059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiometabolic and anxiogenic consequences of chronic social defeat stress in male mice","authors":"Karen A. Scott ,&nbsp;Sophia A. Eikenberry ,&nbsp;Khalid Elsaafien ,&nbsp;Caitlin Baumer-Harrison ,&nbsp;Dominique N. Johnson ,&nbsp;Jéssica Matheus Sá ,&nbsp;Alessandro Bartolomucci ,&nbsp;Colin Sumners ,&nbsp;Eric G. Krause ,&nbsp;Annette D. de Kloet","doi":"10.1016/j.ynstr.2025.100752","DOIUrl":"10.1016/j.ynstr.2025.100752","url":null,"abstract":"<div><div>Social adversity, such as that which occurs during subjugation to a lower social status, has profound psychological and cardiometabolic consequences that are conserved across species. Clinically, such adversity often arises from being of a lower socioeconomic status and may contribute to health disparities in cardiometabolic and affective disorders. To develop a better understanding of the cardiometabolic consequences of social adversity, we employ chronic social defeat stress (CSDS) in adult male mice. CSDS results in increases in body mass, that are accompanied by elevated lean and fluid mass, as well as several somatic indices of chronic stress. Moreover, mice exposed to CSDS exhibit increased anxiety-like behavior, spending more time in the closed arms of the elevated plus maze and less time in the center of an open field arena. Regarding cardiovascular parameters, initial social defeat sessions result in increases in blood pressure, activity, and temperature in comparison with control mice. Interestingly, while blood pressure returns to basal levels by the start of the light cycle for the first few days of defeat, 14 days of CSDS results in sustained elevations in blood pressure, lower activity and lower body temperature. Finally, the results of heart rate variability, spontaneous baroreflex sensitivity and adrenal transcriptome analyses were consistent with CSDS-induced autonomic dysfunction, effects that may contribute to the hypertension observed. Collectively, these data suggest that CSDS may be useful for modeling hypertension induced by chronic social stress, thereby enabling us to better understand the mechanisms that contribute to stress-induced cardiometabolic disease.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"38 ","pages":"Article 100752"},"PeriodicalIF":3.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144886079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sexual dimorphism in anxiety susceptibility: role of PNN maturation timing in the habenulo-interpeduncular reward circuits","authors":"Niels Fjerdingstad,&nbsp;Malalaniaina Rakotobe ,&nbsp;Célia Leboulenger,&nbsp;Adrien Chopin,&nbsp;Thomas Lamonerie,&nbsp;Fabien D'Autréaux","doi":"10.1016/j.ynstr.2025.100750","DOIUrl":"10.1016/j.ynstr.2025.100750","url":null,"abstract":"","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"38 ","pages":"Article 100750"},"PeriodicalIF":3.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144864842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prenatal stress induces transient developmental alterations in distinct GABAergic populations and leads to long-lasting behavioral abnormalities","authors":"Keren Shoshani-Haye ,&nbsp;Gilgi Friedlander ,&nbsp;Ofra Golani ,&nbsp;Suellen Almeida-Correa ,&nbsp;Yair Shemesh ,&nbsp;Alon Chen","doi":"10.1016/j.ynstr.2025.100749","DOIUrl":"10.1016/j.ynstr.2025.100749","url":null,"abstract":"<div><div>Prenatal stress (PNS) is a well-established risk factor for psychiatric disorders, yet the underlying neurobiological mechanisms remain unclear. Here, we demonstrate that PNS induces long-term behavioral abnormalities, including increased anxiety- and depressive-like behaviors specifically in adult male mice. To investigate potential neurodevelopmental disruptions, we analyzed the medial prefrontal cortex (mPFC) at key postnatal stages. RNA sequencing at postnatal day 1 (P1) revealed significant transcriptional changes, particularly in genes associated with neuronal migration and differentiation, with a diminished effect by P14. Histological analysis identified a transient imbalance in inhibitory neuron subpopulations, PNS decreased the density of early-born neurons derived from the medial ganglionic eminence (MGE) while increasing late-born neurons derived from the caudal ganglionic eminence (CGE) at P1. EdU labeling confirmed that these shifts were time- and subtype-specific, affecting inhibitory neuron proliferation at distinct embryonic stages. By P15, these neuroanatomical alterations largely resolved, yet behavioral abnormalities persisted into adulthood. Our findings suggest that PNS disrupts inhibitory neuron development during a critical early window, leading to lasting behavioral consequences despite the transient nature of anatomical changes. This study highlights the selective vulnerability of inhibitory neuron subtypes to early-life stress and provides insight into potential mechanisms underlying stress-related psychiatric disorders.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"38 ","pages":"Article 100749"},"PeriodicalIF":3.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144858037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interactive effects of early life adversity and adolescent basolateral amygdala activity on corticolimbic connectivity and behavior","authors":"Caitlyn R. Cody ,&nbsp;Emilce Artur de la Villarmois ,&nbsp;Anabel M.M. Miguelez Fernández ,&nbsp;Janelle P. Lardizabal ,&nbsp;Kuei Y. Tseng ,&nbsp;Heather C. Brenhouse","doi":"10.1016/j.ynstr.2025.100753","DOIUrl":"10.1016/j.ynstr.2025.100753","url":null,"abstract":"<div><div>Corticolimbic development is shaped by the environment and relies on coordinated neuronal activity. Prior work revealed that early life adversity (ELA) leads to hyperinnervation of basolateral amygdala (BLA) projections to the prefrontal cortex (PFC) beginning in early adolescence. Both ELA and corticolimbic hyperconnectivity are associated with anxiety-like behavior, however the underlying developmental processes driving these effects are largely unknown. Here we investigated interactive impacts of rearing environment and neuronal activity on behavior and corticolimbic connectivity in rats. We first found that BLA-PFC hyperinnervation was associated with enhanced BLA-evoked PFC local field potentials in adolescents exposed to maternal separation (MS) ELA. Since ELA reportedly increases activity in the early-developing BLA, we further examined whether reducing BLA activity during adolescence influences behavior or enduring PFC innervation. During early adolescence, MS animals displayed heightened exploratory behaviors in an open field. Differences between rearing groups were not present during acute inhibition of glutamatergic BLA neurons, as BLA inhibition resembled the effects of MS on adolescent exploratory behaviors. To examine longer-lasting impacts of adolescent BLA activity on PFC innervation, BLA-originating axonal boutons were quantified in the PFC during emerging adulthood after adolescent BLA inhibition. We expanded previous findings to show that MS causes enduring BLA-PFC hyperinnervation. Surprisingly, adolescent BLA inhibition itself increased BLA-PFC innervation in control animals, suggesting that hyperpolarization of output neurons during early adolescence may contribute to aberrant development of efferent projections. Taken together, our results indicate that ELA yields increased BLA-PFC innervation in adulthood that may involve enhanced inhibitory signaling within developing BLA circuitry.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"38 ","pages":"Article 100753"},"PeriodicalIF":3.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144892810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptomic profiles of susceptibility and resilience to stress in the amygdala and hippocampus of male rats","authors":"Kimberly L.P. Long ,&nbsp;Sandra E. Muroy ,&nbsp;Siamak K. Sorooshyari ,&nbsp;Mee Jung Ko ,&nbsp;Yanabah Jaques ,&nbsp;Kishant Mohan ,&nbsp;Peter Sudmant ,&nbsp;Daniela Kaufer","doi":"10.1016/j.ynstr.2025.100754","DOIUrl":"10.1016/j.ynstr.2025.100754","url":null,"abstract":"<div><div>Traumatic experiences elicit a wide range of cognitive responses in both humans and animals, leading to diverse outcomes such as enhanced performance, cognitive impairment, or the development of mood and anxiety disorders like posttraumatic stress disorder (PTSD). A key challenge in understanding these varied responses is to decipher the underlying biological mechanisms that contribute to individual variability in trauma resilience or susceptibility. The purpose of this study was to elucidate the molecular bases for these differences, focusing on the amygdala and hippocampus—brain regions integral to stress responses. We exposed adult, male rats to an acute, severe stressor and profiled persistent anxiety-like behavior outcomes 7 days later. We investigated the transcriptional signatures in the basolateral amygdala and hippocampal dentate gyrus via bulk RNA sequencing from animals with behavioral outcomes indicative of stress resilience or vulnerability. Our results suggest that the basolateral amygdala and dentate gyrus display distinct transcriptomic changes following acute, severe stress. Furthermore, we identified specific region-dependent genes related to insulin signaling, neural plasticity, and stress responses that correlate with resilient and vulnerable phenotypes. Notably, a larger number of genes separated stress-resilient animals from both control and stress-susceptible animals, underscoring that an active molecular response, particularly in the hippocampus, facilitates protection from the long-term consequences of severe stress. These findings provide novel insight into the mechanisms that engender individual variability in the behavioral responses to stress and offer new targets for the advancement of therapies for stress-induced neuropsychiatric disorders.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"38 ","pages":"Article 100754"},"PeriodicalIF":3.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144932711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Not just a witness: Highlighting the utility of witness social defeat stress for the examination of neuroimmune-cardiovascular interactions across diverse populations","authors":"Margherita Barbetti ,&nbsp;Cora E. Smiley ,&nbsp;Monia Savi ,&nbsp;Andrea Sgoifo ,&nbsp;Susan K. Wood ,&nbsp;Luca Carnevali","doi":"10.1016/j.ynstr.2025.100751","DOIUrl":"10.1016/j.ynstr.2025.100751","url":null,"abstract":"<div><div>Exposure to stress has widespread pathological consequences in terms of neuropsychiatric disorders and cardiovascular disease. Psychosocial stressors represent the most highly impactful and commonly experienced form of stress and, in preclinical studies, have been found to induce distinct overlapping immune and cardiovascular alterations. Historically, the social defeat model has been fundamental in providing insights into the autonomic and neuroimmune mediators of cardiovascular dysfunction in the face of social stress exposure. However, this procedure relies on aggressive, physical interaction between rodents and is limited by its almost exclusive application to young adult males. This challenges the possibility of using social defeat to generate data in rodents that can be translated into social stress-related processes in both men and women across the lifespan. More recently, a novel vicarious social defeat procedure has been developed, wherein a rodent bears witness to an aggressive social defeat encounter between two males from the safety of an adjacent compartment. This review first discusses the existing data regarding stress-induced cardiovascular alterations and the underlying autonomic and neuroimmune mediators of social defeat while critically discussing the limitations of this model. New prospects are then offered based on recent findings across a diverse population of rodent species, sexes, and ages to support the use of vicarious/witness social defeat model as an optimal strategy to investigate social stress-related autonomic, neuroimmune, and cardiovascular processes using more comprehensive and inclusive methods.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"38 ","pages":"Article 100751"},"PeriodicalIF":3.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144851864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deep brain stimulation changes locus coeruleus responses to social stress from activation to inhibition.","authors":"Sonia Torres-Sanchez, Andre L Curtis, Rita J Valentino, Esther Berrocoso","doi":"10.1016/j.ynstr.2025.100745","DOIUrl":"10.1016/j.ynstr.2025.100745","url":null,"abstract":"<p><p>Deep Brain Stimulation (DBS) of the subgenual cingulate cortex (SCC) stands as an innovative therapeutic approach for treatment-resistant depression. Previous preclinical investigations utilizing DBS targeted at the ventromedial prefrontal cortex (vmPFC), considered the rodent equivalent of the human SCC, have demonstrated antidepressant-like effects, as well as enhancement in the activity of the locus coeruleus (LC)-norepinephrine (NE) system and pontine-cortical network oscillations. Given the association between social stress and depression and other psychiatric disorders, we assessed the impact of vmPFC DBS on social stress-induced changes in LC neuronal activity in awake rats. Spontaneous and auditory-evoked LC single unit activity were compared between control and DBS male rats during the first (acute) and fifth (repeated) day of social defeat stress. In stark contrast to LC activation observed in controls, both acute and repeated stress robustly inhibited LC neurons of DBS rats. While both groups experienced an acute stress-induced reduction in auditory-evoked LC discharge, the duration of the evoked response was only decreased in control animals. LC auditory-evoked activity was increased after repeated stress and DBS effectively counteracted these stress-induced alterations. These findings suggest that DBS treatment shifts stress-induced regulation of LC activity such that it favors the engagement of inhibitory modulation. This may serve to promote resistance of the LC-NE system to stress-induced excitation and contribute to the mitigation of neuropsychiatric consequences of stress.</p>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"38 ","pages":"100745"},"PeriodicalIF":3.6,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12357051/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144874216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interhemispheric Effects of iTBS on the Fronto-Parietal Network: Evidence from Dual-Site Stimulation","authors":"Isabell Int-Veen ,&nbsp;Beatrix Barth ,&nbsp;Ramona Täglich ,&nbsp;Betti Schopp ,&nbsp;Hans-Christoph Nuerk ,&nbsp;Christian Plewnia ,&nbsp;Stefanie De Smet ,&nbsp;Marie-Anne Vanderhasselt ,&nbsp;Andreas J. Fallgatter ,&nbsp;Ann-Christine Ehlis ,&nbsp;David Rosenbaum","doi":"10.1016/j.ynstr.2025.100744","DOIUrl":"10.1016/j.ynstr.2025.100744","url":null,"abstract":"<div><div>This study investigated the neuromodulatory effects of Theta Burst Stimulation (TBS) on resting-state functional connectivity (FC) following psychosocial stress induced by the Trier Social Stress Test (TSST). Given its key role in cognitive control and emotion regulation — processes highly relevant for rumination — we focused on the frontoparietal network. Across two studies, intermittent (iTBS) and continuous (cTBS) protocols were applied to the left Dorsolateral Prefrontal Cortex (DLPFC; study 1) and right Ventrolateral Prefrontal Cortex (VLPFC; study 2) prior to stress induction. Functional Near-Infrared Spectroscopy (fNIRS) was used to assess neural changes. A total of 88 (study 1) and 89 (study 2) healthy participants were recruited, balanced for low and high trait rumination. Each participant received both active and sham TBS (iTBS or cTBS), in a randomized, counterbalanced design. Results indicated that iTBS elicited excitatory effects on prefrontal and fronto-parietal connectivity, whereas cTBS effects were more variable. Trait rumination emerged as a modulator of TBS effects: In study 1, significant interactions for FC between the right VLPFC and Somatosensory Association Cortex (SAC) when stimulating the left DLPFC emerged, while study 2 revealed similar interactions for FC between the left DLPFC and SAC and intra-SAC FC when stimulating the right VLPFC. Correlations between post-stress state rumination and FC changes further support these findings. These results underscore the importance of neural assessments in TBS research and highlight the complexity of individual differences in state and trait rumination. Understanding the interplay between TBS, fronto-parietal connectivity, and rumination may provide valuable insights into personalized neuromodulation strategies.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"37 ","pages":"Article 100744"},"PeriodicalIF":4.3,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144633523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tracking conditioned fear in pair-housed mice using deep learning and real-time cue delivery","authors":"Hannah C. Smith ,&nbsp;Zhe Yu ,&nbsp;Patrick Yazigi ,&nbsp;Benjamin Turley ,&nbsp;Adam P. Swiercz ,&nbsp;Jeanie Park ,&nbsp;Paul J. Marvar","doi":"10.1016/j.ynstr.2025.100742","DOIUrl":"10.1016/j.ynstr.2025.100742","url":null,"abstract":"<div><div>Post-traumatic stress disorder (PTSD) is a complex and prevalent neuropsychiatric condition that arises in response to exposure to a traumatic event. A common diagnostic criterion for PTSD includes heightened physiological reactivity to trauma-related sensory cues, in safe or familiar environments. Understanding complex PTSD criteria requires new pre-clinical paradigms and technologies that integrate sensory physiology (e.g., auditory, visual, olfactory) with behavior. Here we present a novel Pavlovian-based paradigm using an open-source software plus deep learning-based pose estimation to investigate the effects of a recurrent conditioned stimulus (CS) on fear behaviors in pair-housed mice within the home cage. Simultaneous home cage video recording and analysis of CS-evoked freezing behaviors were performed using a deep learning model, with consideration for light-dark circadian cycles. Fear-conditioned dyad mice exhibited high CS-evoked freezing, with evidence of extinction learning (characterized by low freezing) during the mid-phase of the 2-week paradigm. Females exhibited reduced CS-evoked home cage freezing compared to males with circadian differences between the light (low freezing) and dark (high freezing) periods. Following the 2-week paradigm, fear-conditioned mice, compared to controls, exhibited heightened context-dependent freezing, while males but not females showed heightened startle reactivity. Taken together, these results demonstrate a novel software application for examining conditioned defensive and fear behaviors over time in mouse dyads within an ethologically relevant environment. Future applications could be used for more integrative analysis and understanding of neural circuits and heightened sensory threat reactivity, potentially improving the understanding and treatment of PTSD.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"37 ","pages":"Article 100742"},"PeriodicalIF":4.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144490495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}