Generalization and extinction of platform-mediated avoidance in male and female rats DOI Creative Commons
Alba López-Moraga, Laura Luyten, Tom Beckers

et al.

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

Published: Oct. 18, 2024

Abstract Background Understanding the basis of anxiety-related disorders can be advanced by studying fear learning mechanisms implicated in transition from adaptive to maladaptive fear. Individuals with anxiety typically exhibit impaired extinction, pervasive avoidance, and overgeneralization While most research has examined deviations these characteristics isolation, their potential interactions remain understudied. Here, we introduce a modification platform-mediated avoidance task use it chart generalization, extinction using single procedure male female rats. Results In first experiment, demonstrated that rats readily acquire show gradient generalization two-day test, gradually reduce responding under extinction. second likewise exhibited successful learning, showed gradual defensive behaviors. Across both experiments, interesting sex differences emerged. The third experiment aimed at corroborating but they were subtler than expected prior separate experiments. Finally, present an open-source automated system facilitate processing DeepLabCut SimBA output obtain reliable results for scoring freezing behavior. Conclusions modified effectively probe procedure. Our behavioral approach offers researchers efficient reproducible method quantify behaviors darting

Language: Английский

The central nucleus of the amygdala and the construction of defensive modes across the threat-imminence continuum DOI
Justin M. Moscarello, Mario A. Penzo

Nature Neuroscience, Journal Year: 2022, Volume and Issue: 25(8), P. 999 - 1008

Published: Aug. 1, 2022

Language: Английский

Citations

72
Top-down control of flight by a non-canonical cortico-amygdala pathway DOI
Chandrashekhar D. Borkar, Claire E. Stelly, Xin Fu

et al.

Nature, Journal Year: 2024, Volume and Issue: 625(7996), P. 743 - 749

Published: Jan. 17, 2024

Language: Английский

Citations

17
Darting across space and time: parametric modulators of sex-biased conditioned fear responses DOI Open Access
J. Mitchell, Sean G. Trettel, Anna J. Li

et al.

Learning & Memory, Journal Year: 2022, Volume and Issue: 29(7), P. 171 - 180

Published: June 16, 2022

Pavlovian fear conditioning is a widely used behavioral paradigm for studying associative learning in rodents. Despite early recognition that subjects may engage variety of both conditioned and unconditioned responses, the last several decades have seen field narrow its focus to measure freezing as sole indicator fear. We previously reported female rats were more likely than males darting, an escape-like response associated with heightened shock reactivity. To determine how experimental parameters contribute frequency darting females, we manipulated factors such chamber size, intensity, number trials. better capture fear-related repertoires our animals, developed ScaredyRat, open-source custom Python tool analyzes Noldus Ethovision-generated raw data files identify darters quantify responses. found that, like freezing, occurrences scale alterations. While most occurs extended training protocol, can emerge well. Collectively, suggest reflects switch responding product individual animal's sex, reactivity, parameters, underscoring need careful consideration sex biological variable classic paradigms.

Language: Английский

Citations

62
Conditional and unconditional components of aversively motivated freezing, flight and darting in mice DOI Creative Commons
Jeremy M. Trott, Ann N. Hoffman,

Irina Zhuravka

et al.

eLife, Journal Year: 2022, Volume and Issue: 11

Published: May 26, 2022

Fear conditioning is one of the most frequently used laboratory procedures for modeling learning and memory generally, anxiety disorders in particular. The conditional response (CR) majority fear studies rodents freezing. Recently, it has been reported that under certain conditions, running, jumping, or darting replaces freezing as dominant CR. These findings raise both a critical methodological problem an important theoretical issue. If only measured but express their with different response, then significant instances learning, memory, may be missed. In terms theory, whatever conditions lead to these behaviors key how animals transition between defensive responses emotional states. mice, we replicated past results along several novel control conditions. Contrary prior conclusions, running were primarily result nonassociative processes actually suppressed by associative learning. Darting flight taken analogous startle alpha are potentiated fear. Additionally, had some impact on topography behavior. On other hand, was purest reflection We also uncovered rule describes when movements replace freezing: afraid, freeze until there sudden change stimulation, burst into vigorous attempts. This govern from panic.

Language: Английский

Citations

57
Anxiety, fear, panic: An approach to assessing the defensive behavior system across the predatory imminence continuum DOI Creative Commons
Ann N. Hoffman, Jeremy M. Trott,

Anna S. Makridis

et al.

Learning & Behavior, Journal Year: 2022, Volume and Issue: 50(3), P. 339 - 348

Published: Feb. 2, 2022

In order to effectively thwart predation, antipredator defensive behaviors must be matched the current spatio-temporal relationship predator. We have proposed a model where different responses are organized along predatory imminence continuum (PIC). The PIC is behavior system as sequence of innately programmed behavioral modes, each representing interaction with predator or threat. Ranging from low threat contact, categorizes defense modes pre-encounter, post-encounter, and circa-strike, corresponding states anxiety, fear, panic, respectively. This experiment examined if same significant stressor caused overexpression all PIC, including anxiety-like behavior, freezing, panic-like responses. Female male mice were exposed acute stress that consisted series ten pseudorandomly presented unsignaled footshocks (or no shocks). Mice subsequently tested on battery tasks assess effects pre-encounter (anxiety-like), post-encounter (fear), circa-strike (panic-like) behaviors. Results revealed following stress, exhibited increased shown through reduced average velocity within modified open field. Furthermore, stressed showed fear single footshock in new context well an increase reactivity white noise original context, exhibiting more robust circa-strike-like response than controls. Therefore, exposure influenced panic across continuum. research could therefore reveal how such become maladaptive traumatic humans.

Language: Английский

Citations

39
Dietary Protection against Cognitive Impairment, Neuroinflammation and Oxidative Stress in Alzheimer’s Disease Animal Models of Lipopolysaccharide-Induced Inflammation DOI Open Access
Davide Decandia, Francesca Gelfo, Eugenia Landolfo

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(6), P. 5921 - 5921

Published: March 21, 2023

Alzheimer’s disease (AD) is a rapidly growing epidemic with heavy social and economic burden. Evidence suggests that systemic inflammation, dysregulation of the immune response resulting neuroinflammation neurodegeneration play significant role in AD pathogenesis. Currently, given there no fully convincing cure for AD, interest lifestyle factors (such as diet), which potentially delay onset reduce severity symptoms, increasing. This review aimed at summarizing effects dietary supplementation on cognitive decline, oxidative stress AD-like animal models focus induced by lipopolysaccharide (LPS) injection, mimics inflammation animals. The compounds reviewed include curcumin, krill oil, chicoric acid, plasmalogens, lycopene, tryptophan-related dipeptides, hesperetin selenium peptides. Despite heterogeneity these compounds, strong consensus their counteracting action LPS-induced deficits neuroinflammatory responses rodents modulating cell-signaling processes, such NF-κB pathway. Overall, interventions could represent an important resource to oppose due influence neuroprotection regulation.

Language: Английский

Citations

28
A fear conditioned cue orchestrates a suite of behaviors in rats DOI Creative Commons
Amanda Chu,

Nicholas T Gordon,

Aleah M DuBois

et al.

eLife, Journal Year: 2024, Volume and Issue: 13

Published: May 21, 2024

Pavlovian fear conditioning has been extensively used to study the behavioral and neural basis of defensive systems. In a typical procedure, cue is paired with foot shock, subsequent presentation elicits freezing, behavior theoretically linked predator detection. Studies have since shown conditioned can elicit locomotion, that – in addition jumping, rearing imminent or occurring predation. A criticism studies observing cue-elicited locomotion responding non-associative. We gave rats discrimination over baseline reward seeking. TTL-triggered cameras captured 5 frames/s around presentation. Experiment 1 examined emergence danger-specific behaviors acquisition. 2 expression extinction. total, we scored 112,000 frames for nine discrete categories. Temporal ethograms show during acquisition, suppresses seeking but also all which are maximal when shock imminent. During extinction, most prominently seeking, timed delivery. The independent these both experiments reveals orchestrate temporally organized suite behaviors.

Language: Английский

Citations

16
Neural Oscillations in Aversively Motivated Behavior DOI Creative Commons
Michael S. Totty, Stephen Maren

Frontiers in Behavioral Neuroscience, Journal Year: 2022, Volume and Issue: 16

Published: July 1, 2022

Fear and anxiety-based disorders are highly debilitating among the most prevalent psychiatric disorders. These associated with abnormal network oscillations in brain, yet a comprehensive understanding of role regulation aversively motivated behavior is lacking. In this review, we examine oscillatory correlates fear anxiety particular focus on rhythms theta gamma-range. First, describe neural their link to function by detailing well-studied gamma spatial memory functions hippocampus. We then how act synchronize brain structures guide adaptive anxiety-like behavior. short, that hippocampal integrate information motivationally salient from amygdala during states before routing via appropriate target regions, such as prefrontal cortex. Moreover, develop neocortical areas encoding memories, interregional synchronization reflects retrieval both recent remotely encoded memories. Finally, argue thalamic nucleus reuniens represents key node synchronizing prefrontal-hippocampal dynamics for episodic extinction memories

Language: Английский

Citations

23
Sex differences in the immediate extinction deficit and renewal of extinguished fear in rats DOI Creative Commons

Annalise N. Binette,

Michael S. Totty, Stephen Maren

et al.

PLoS ONE, Journal Year: 2022, Volume and Issue: 17(6), P. e0264797 - e0264797

Published: June 10, 2022

Extinction learning is central to exposure-based behavioral therapies for reducing fear and anxiety in humans. However, patients with disorders are often resistant extinction. Moreover, trauma stress-related highly prone relapse twice as likely occur females compared males, suggesting that may be more susceptible extinction deficits phenomena. In this report, we tested hypothesis by examining sex differences a stress-induced impairment, the immediate deficit (IED), renewal, common form of relapse. contrast our hypothesis, there were no magnitude two different rat strains (Long-Evans Wistar). did observe difference renewal when extinguished conditioned stimulus was presented outside context. Male Wistar rats exhibited significantly greater than female rats, has previously been reported after appetitive Collectively, these data reveal impairments similar male though context-dependence pronounced males.

Language: Английский

Citations

20
Sex difference affects fear extinction but not lithium efficacy in rats following fear-conditioning with respect to the hippocampal level of BDNF DOI
Mehrsa Rahimi-Danesh, Mohammad-Ali Samizadeh,

Amir-Ehsan Sajadi

et al.

Pharmacology Biochemistry and Behavior, Journal Year: 2023, Volume and Issue: 234, P. 173675 - 173675

Published: Nov. 14, 2023

Language: Английский

Citations

12