Strain Differences in Acquisition and Extinction of Fear Responses in Rats

5 different strains of rats (Roman high and low avoiders, Maudsley reactive and non-reactive and random-bred animals) were subjected repeatedly to extinction trials following Pavlovian fear conditioning. The duration of the extinction trials was varied for different groups of animals. Fear was measured by latency of escape into the “safe” compartment in Exp. I and by step-down latency in Exp. II during a final fear-retention test. Results showed no differences between Roman high and low avoiders; for the Maudsley strains, however, results suggested that the higher the basal fear level the stronger is the acquired fear response and the more time is required for its extinction. Fearfulness in the animal and duration of extinction trials were jointly and severally causal in determining degree of extinction of the conditioned fear response.

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Medial Orbitofrontal Cortex Regulates Instrumental Conditioned Punishment, but not Pavlovian Conditioned Fear

Cerebral Cortex Communications ◽

10.1093/texcom/tgaa039 ◽

2020 ◽

Author(s):

Cassandra Ma ◽

Philip Jean-Richard-dit-Bressel ◽

Stephanie Roughley ◽

Bryce Vissel ◽

Bernard W Balleine ◽

...

Keyword(s):

Fear Conditioning ◽

Orbitofrontal Cortex ◽

Conditioned Fear ◽

Causal Link ◽

Pavlovian Fear Conditioning ◽

Compulsive Disorders ◽

Sensitivity To Punishment

Abstract Bidirectionally aberrant medial orbitofrontal cortical (mOFC) activity has been consistently linked with compulsive disorders and related behaviors. Although rodent studies have established a causal link between mOFC excitation and compulsive-like actions, no such link has been made with mOFC inhibition. Here we use excitotoxic lesions of mOFC to investigate its role in sensitivity to punishment; a core characteristic of many compulsive disorders. In our first experiment, we demonstrated that mOFC lesions prevented rats from learning to avoid a lever that was punished with a stimulus that co-terminated with footshock. Our second experiment demonstrated that retrieval of punishment learning is also somewhat mOFC-dependent, as lesions prevented the extended retrieval of punishment contingencies relative to shams. In contrast, mOFC lesions did not prevent rats from re-acquiring the ability to avoid a punished lever when it was learned prior to lesions being administered. In both experiments, Pavlovian fear conditioning to the stimulus was intact for all animals. Together, these results reveal that the mOFC regulates punishment learning and retrieval in a manner that is separate from any role in Pavlovian fear conditioning. These results imply that aberrant mOFC activity may contribute to the punishment insensitivity that is observed across multiple compulsive disorders.

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Impairment in acquisition of conditioned fear in schizophrenia: a pooled analysis of four studies

10.1101/2021.05.26.21257857 ◽

2021 ◽

Author(s):

Lauri Tuominen ◽

Liana Romaniuk ◽

Mohammed R Milad ◽

Donald C Goff ◽

Jeremy Hall ◽

...

Keyword(s):

Associative Learning ◽

Fear Conditioning ◽

Conditioned Fear ◽

Pooled Analysis ◽

Control Group ◽

Pavlovian Fear Conditioning ◽

Schizophrenia Group ◽

Skin Conductance Responses ◽

Sufficient Power ◽

Prior Models

Background: Individuals with schizophrenia show impairments in associative learning. One well-studied, quantifiable form of associative learning is Pavlovian fear conditioning. However, to date, studies of fear conditioning in schizophrenia have been inconclusive, possibly because they lacked sufficient power. Methods: To address this issue, data were pooled from 4 independent fear conditioning studies that included a total of 77 individuals with schizophrenia and 74 control subjects. Skin conductance responses (SCRs) during fear conditioning to stimuli that were paired (the CS+) and not paired (CS-) with an aversive, unconditioned stimulus were measured, and the success of acquisition of differential conditioning (the magnitude of CS+ vs CS- SCRs) and responses to CS+ and CS- separately were assessed. Results: Acquisition of differential conditioned fear responses was significantly lower in individuals with schizophreania than in healthy controls (Cohen's d = 0.53). This effect was primarily related to a significantly higher response to the CS- stimulus in the schizophrenia compared to the control group. The magnitude of this response to the CS- in the schizophrenia group was correlated with the severity of delusional ideation. Other symptoms or antipsychotic dose were not associated with fear conditioning measures. Conclusions: Individuals with schizophrenia who endorse delusional beliefs are over-responsive to neutral stimuli during fear conditioning. This finding is consistent with prior models of aberrant learning in psychosis.

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Isoflurane Causes Anterograde but Not Retrograde Amnesia for Pavlovian Fear Conditioning

Anesthesiology ◽

10.1097/00000542-200205000-00027 ◽

2002 ◽

Vol 96 (5) ◽

pp. 1223-1229 ◽

Cited By ~ 25

Author(s):

Robert C. Dutton ◽

Anya J. Maurer ◽

James M. Sonner ◽

Michael S. Fanselow ◽

Michael J. Laster ◽

...

Keyword(s):

Fear Conditioning ◽

Retrograde Amnesia ◽

Minimum Alveolar Concentration ◽

Conditioned Fear ◽

Pavlovian Fear Conditioning ◽

Conditioning Procedure ◽

Trial Procedure ◽

Learning Procedure ◽

The One ◽

Dose Dependent

Background Production of retrograde amnesia by anesthetics would indicate that these drugs can disrupt mechanisms that stabilize memory. Such disruption would allow suppression of memory of previous untoward events. The authors examined whether isoflurane provides retrograde amnesia for classic (Pavlovian) fear conditioning. Methods Rats were trained to fear tone by applying three (three-trial) or one (one-trial) tone-shock pairs while breathing various constant concentrations of isoflurane. Immediately after training, isoflurane administration was either discontinued, maintained unchanged, or rapidly increased to 1.0 minimum alveolar concentration for 1 h longer. Groups of rats were similarly trained to fear context while breathing isoflurane by applying shocks (without tones) in a distinctive environment. The next day, memory for the conditioned stimuli was determined by presenting the tone or context (without shock) and measuring the proportion of time each rat froze (appeared immobile). For each conditioning procedure, the effects of the three posttraining isoflurane treatments were compared. Results Rapid increases in posttraining isoflurane administration did not suppress conditioned fear for any of the training procedures. In contrast, isoflurane administration during conditioning dose-dependently suppressed conditioning (P < 0.05). Training to tone was more resistant to the effects of isoflurane than training to context (P < 0.05), and the three-trial learning procedure was more was more resistant than the one-trial procedure (P < 0.05). Conclusions Isoflurane provided intense dose-dependent anterograde but not retrograde amnesia for classic fear conditioning. Isoflurane appears to disrupt memory processes that occur at or within a few minutes of the conditioning procedure.

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Sexually divergent expression of active and passive conditioned fear responses in rats

eLife ◽

10.7554/elife.11352 ◽

2015 ◽

Vol 4 ◽

Cited By ~ 110

Author(s):

Tina M Gruene ◽

Katelyn Flick ◽

Alexis Stefano ◽

Stephen D Shea ◽

Rebecca M Shansky

Keyword(s):

Fear Conditioning ◽

Conditioned Fear ◽

Female Rats ◽

Fear Response ◽

Long Term Outcomes ◽

Response Strategies ◽

Extinction Testing ◽

Learned Fear ◽

Fear Behavior

Traditional rodent models of Pavlovian fear conditioning assess the strength of learning by quantifying freezing responses. However, sole reliance on this measure includes the de facto assumption that any locomotor activity reflects an absence of fear. Consequently, alternative expressions of associative learning are rarely considered. Here we identify a novel, active fear response (‘darting’) that occurs primarily in female rats. In females, darting exhibits the characteristics of a learned fear behavior, appearing during the CS period as conditioning proceeds and disappearing from the CS period during extinction. This finding motivates a reinterpretation of rodent fear conditioning studies, particularly in females, and it suggests that conditioned fear behavior is more diverse than previously appreciated. Moreover, rats that darted during initial fear conditioning exhibited lower freezing during the second day of extinction testing, suggesting that females employ distinct and adaptive fear response strategies that improve long-term outcomes.

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The Effects of MRNA synthesis in the Amygdala on the Acquisition and Reconsolidation of Pavlovian Fear Conditioning

PsycEXTRA Dataset ◽

10.1037/e413812005-447 ◽

2002 ◽

Author(s):

Ryan G. Parsons ◽

Georgette M. Gafford ◽

Fred J. Helmstetter

Keyword(s):

Fear Conditioning ◽

Pavlovian Fear Conditioning ◽

Mrna Synthesis

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The evaluation of Teucrium persicum methanolic extract and its fractions in Pavlovian Fear Conditioning

Planta Medica ◽

10.1055/s-0031-1282962 ◽

2011 ◽

Vol 77 (12) ◽

Author(s):

H Monsef Esfahani ◽

M Sharifzadeh ◽

M Moattari ◽

A Miri ◽

E Nasireslami

Keyword(s):

Fear Conditioning ◽

Methanolic Extract ◽

Pavlovian Fear Conditioning

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Faculty Opinions recommendation of Auditory-evoked spike firing in the lateral amygdala and Pavlovian fear conditioning: mnemonic code or fear bias?

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1017805.207445 ◽

2004 ◽

Author(s):

Wendy Suzuki

Keyword(s):

Fear Conditioning ◽

Pavlovian Fear Conditioning ◽

Lateral Amygdala ◽

Spike Firing

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Fear-induced brain activations distinguish anxious and trauma-exposed brains

Translational Psychiatry ◽

10.1038/s41398-020-01193-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Zhenfu Wen ◽

Marie-France Marin ◽

Jennifer Urbano Blackford ◽

Zhe Sage Chen ◽

Mohammed R. Milad

Keyword(s):

Neural Network ◽

Fear Conditioning ◽

Psychiatric Diagnosis ◽

Data Analytics ◽

Conditioned Fear ◽

Brain Regions ◽

Brain Network ◽

Neuroimaging Data ◽

Task Irrelevant ◽

Translational Models

AbstractTranslational models of fear conditioning and extinction have elucidated a core neural network involved in the learning, consolidation, and expression of conditioned fear and its extinction. Anxious or trauma-exposed brains are characterized by dysregulated neural activations within regions of this fear network. In this study, we examined how the functional MRI activations of 10 brain regions commonly activated during fear conditioning and extinction might distinguish anxious or trauma-exposed brains from controls. To achieve this, activations during four phases of a fear conditioning and extinction paradigm in 304 participants with or without a psychiatric diagnosis were studied. By training convolutional neural networks (CNNs) using task-specific brain activations, we reliably distinguished the anxious and trauma-exposed brains from controls. The performance of models decreased significantly when we trained our CNN using activations from task-irrelevant brain regions or from a brain network that is irrelevant to fear. Our results suggest that neuroimaging data analytics of task-induced brain activations within the fear network might provide novel prospects for development of brain-based psychiatric diagnosis.

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Fear conditioning and stimulus generalization in association with age in children and adolescents

European Child & Adolescent Psychiatry ◽

10.1007/s00787-021-01797-4 ◽

2021 ◽

Author(s):

Julia Reinhard ◽

Anna Slyschak ◽

Miriam A. Schiele ◽

Marta Andreatta ◽

Katharina Kneer ◽

...

Keyword(s):

Children And Adolescents ◽

Fear Conditioning ◽

Repeated Measures ◽

Conditioned Fear ◽

Fear Learning ◽

Stimulus Generalization ◽

Healthy Children ◽

Older Individuals ◽

Age Related ◽

Current Task

AbstractThe aim of the study was to investigate age-related differences in fear learning and generalization in healthy children and adolescents (n = 133), aged 8–17 years, using an aversive discriminative fear conditioning and generalization paradigm adapted from Lau et al. (2008). In the current task, participants underwent 24 trials of discriminative conditioning of two female faces with neutral facial expressions, with (CS+) or without (CS−) a 95-dB loud female scream, presented simultaneously with a fearful facial expression (US). The discriminative conditioning was followed by 72 generalization trials (12 CS+, 12 GS1, 12 GS2, 12 GS3, 12 GS4, and 12 CS−): four generalization stimuli depicting gradual morphs from CS+ to CS− in 20%-steps were created for the generalization phases. We hypothesized that generalization in children and adolescents is negatively correlated with age. The subjective ratings of valence, arousal, and US expectancy (the probability of an aversive noise following each stimulus), as well as skin conductance responses (SCRs) were measured. Repeated-measures ANOVAs on ratings and SCR amplitudes were calculated with the within-subject factors stimulus type (CS+, CS−, GS1-4) and phase (Pre-Acquisition, Acquisition 1, Acquisition 2, Generalization 1, Generalization 2). To analyze the modulatory role of age, we additionally calculated ANCOVAs considering age as covariate. Results indicated that (1) subjective and physiological responses were generally lower with increasing age irrespective to the stimulus quality, and (2) stimulus discrimination improved with increasing age paralleled by reduced overgeneralization in older individuals. Longitudinal follow-up studies are required to analyze fear generalization with regard to brain maturational aspects and clarify whether overgeneralization of conditioned fear promotes the development of anxiety disorders or vice versa.

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