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

eLife ◽  
2015 ◽  
Vol 4 ◽  
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.

scholarly journals Vagus Nerve Stimulation Enhances Extinction of Conditioned Fear in Rats and Modulates Arc Protein, CaMKII, and GluN2B-Containing NMDA Receptors in the Basolateral Amygdala

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Amanda C. Alvarez-Dieppa ◽  
Kimberly Griffin ◽  
Sheridan Cavalier ◽  
Christa K. McIntyre
Keyword(s):  
Synaptic Plasticity ◽  
Vagus Nerve ◽  
Nmda Receptors ◽  
Fear Conditioning ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Basolateral Amygdala ◽  
Conditioned Fear ◽  
Associated Proteins

Vagus nerve stimulation (VNS) enhances the consolidation of extinction of conditioned fear. High frequency stimulation of the infralimbic cortex (IL) produces long-term potentiation in the basolateral amygdala (BLA) in rats given VNS-paired extinction training, whereas the same stimulation produces long-term depression in sham-treated rats. The present study investigated the state of synaptic plasticity-associated proteins in the BLA that could be responsible for this shift. Male Sprague-Dawley rats were separated into 4 groups: auditory fear conditioning only (fear-conditioned); fear conditioning + 20 extinction trials (extended-extinction); fear conditioning + 4 extinction trials paired with sham stimulation (sham-extinction); fear conditioning + 4 extinction trials paired with VNS (VNS-extinction). Freezing was significantly reduced in extended-extinction and VNS-extinction rats. Western blots were used to quantify expression and phosphorylation state of synaptic plasticity-associated proteins such as Arc, CaMKII, ERK, PKA, and AMPA and NMDA receptors. Results show significant increases in GluN2B expression and phosphorylated CaMKII in BLA samples from VNS- and extended-extinction rats. Arc expression was significantly reduced in VNS-extinction rats compared to all groups. Administration of the GluN2B antagonist ifenprodil immediately after fear extinction training blocked consolidation of extinction learning. Results indicate a role for BLA CaMKII-induced GluN2B expression and reduced Arc protein in VNS-enhanced extinction.

scholarly journals Rule-based processes in generalisation and peak shift in human fear conditioning

2018 ◽  
Vol 72 (2) ◽  
pp. 118-131 ◽  
Author(s):  
Ola Ahmed ◽  
Peter F Lovibond
Keyword(s):  
Fear Conditioning ◽  
Electric Shock ◽  
Aversive Stimulus ◽  
Conditioned Fear ◽  
Peak Shift ◽  
Test Phase ◽  
Conditioned Stimuli ◽  
Rule Based ◽  
Extinction Testing

Two experiments explored the role of verbalisable rules in generalisation of human differential fear conditioning with electric shock as the aversive stimulus. Two circles of different sizes served as conditioned stimuli (CS+ and CS–), before testing with a range of circle sizes. In Experiment 1, shock expectancy ratings followed a peak-shifted unimodal gradient, with maximum ratings at a test value further along the dimension from CS+ in the opposite direction to CS–. However, differentiable gradients were observed when participants were divided on the basis of the rules they reported using during the task (linear and similarity). Experiment 2 was designed to counter the contradictory feedback arising from extinction testing by removing the shock electrodes during the test phase. A more linear overall gradient was observed, and sub-groups defined by self-reported rules showed distinct gradients that were congruent with their rules. These results indicate that rule-based processes are influential in generalisation of conditioned fear along simple stimulus dimensions, and may help explain generalisation phenomena that have traditionally been attributed to automatic, similarity-based processes.

The antidepressant agomelatine reduces fear long term memory but not acquisition or short term expression of fear memories

2011 ◽  
Vol 26 (S2) ◽  
pp. 653-653
Author(s):  
L. Diaz-Mataix ◽  
E. Mocaër ◽  
L. Seguin ◽  
J.E. Ledoux
Keyword(s):  
Fear Conditioning ◽  
Clinical Studies ◽  
Conditioned Fear ◽  
Fear Learning ◽  
Long Term Memory ◽  
Onset Of Action ◽  
Subsequent Exposure ◽  
Preclinical And Clinical Studies ◽  
Antidepressant Action

Alterations in fear learning processes may be implicated in mood disorders. Fear learning has been investigated with Pavlovian classical fear conditioning paradigms, consisting of pairing a neutral conditioned stimulus (CS), such as a tone, with an aversive unconditioned stimulus (US), such as a footshock. Upon subsequent exposure, the CS is perceived as aversive and provokes a fear response.The novel antidepressant agomelatine acts as a melatonergic receptor agonist and a 5-HT2C receptor antagonist. Its antidepressant action was demonstrated in preclinical and clinical studies. Agomelatine has also anxiolytic properties. The aim of this study was to determine how acute agomelatine treatment might differentially alter fear circuits by using auditory fear conditioning in the rat.A single pre-training injection of agomelatine (40 mg/kg intraperitoneally) significantly reduced freezing to the fear arousing CS 24 hours after training but not during training or 3 hours after training. This pattern of results is consistent with an effect on the consolidation of the fear memory. A single pre-testing injection of agomelatine had no effect on conditioned fear expression.These effects of agomelatine should be considered in relation to its antidepressant action. Agomelatine achieved a reduction of fear conditioning in a single dose, while classical SSRIs only reduced fear conditioning after chronic treatment. This finding is consistent with clinical studies suggesting a faster onset of action of agomelatine than classical SSRI treatment.

Strain Differences in Acquisition and Extinction of Fear Responses in Rats

1976 ◽  
Vol 38 (1) ◽  
pp. 163-187 ◽  
Author(s):  
Gudrun Sartory ◽  
Hans J. Eysenck
Keyword(s):  
Fear Conditioning ◽  
Retention Test ◽  
Conditioned Fear ◽  
Strain Differences ◽  
Pavlovian Fear Conditioning ◽  
Test Results ◽  
Fear Response ◽  
Maudsley Strains ◽  
Step Down ◽  
Different Strains

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.

scholarly journals Cerebellar molecular layer interneurons are dispensable for cued and contextual fear conditioning

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Katy L. H. Marshall-Phelps ◽  
Gernot Riedel ◽  
Peer Wulff ◽  
Marta Woloszynowska-Fraser
Keyword(s):  
Fear Conditioning ◽  
Purkinje Cells ◽  
Cerebellar Cortex ◽  
Conditioned Fear ◽  
Molecular Layer ◽  
Fear Memory ◽  
Memory Formation ◽  
Contextual Fear Conditioning ◽  
Contextual Fear

AbstractPurkinje cells are the only output cell of the cerebellar cortex. Their spatiotemporal activity is controlled by molecular layer interneurons (MLIs) through GABAA receptor-mediated inhibition. Recently, it has been reported that the cerebellar cortex is required for consolidation of conditioned fear responses during fear memory formation. Although the relevance of MLIs during fear memory formation is currently not known, it has been shown that synapses made between MLIs and Purkinje cells exhibit long term plasticity following fear conditioning. The present study examined the role of cerebellar MLIs in the formation of fear memory using a genetically-altered mouse line (PC-∆γ2) in which GABAA receptor-mediated signaling at MLI to Purkinje cell synapses was functionally removed. We found that neither acquisition nor recall of fear memories to tone and context were altered after removal of MLI-mediated inhibition.

scholarly journals Prolonged Social Isolation, Started Early in Life, Impairs Cognitive Abilities in Rats Depending on Sex

2020 ◽  
Vol 10 (11) ◽  
pp. 799
Author(s):  
Nataliya A. Krupina ◽  
Sophie D. Shirenova ◽  
Nadezhda N. Khlebnikova
Keyword(s):  
Social Isolation ◽  
Cognitive Abilities ◽  
Conditioned Fear ◽  
Relative Weight ◽  
Corticosterone Level ◽  
Female Rats ◽  
Enzyme Linked Immunosorbent Assay ◽  
Dependent Manner ◽  
Housing Conditions

Background: The chronic stress of social isolation is a valid predictor of cognitive pathology. This study aimed to compare the effects of long-term social isolation on female versus male Wistar rats’ learning and memory. We hypothesized that prolonged social isolation stress, which starts early in life, would affect learning in a sex-dependent manner. Methods: Social isolation started at the edge of early to mid-adolescence and lasted 9 months. The rat’s cognitive abilities were assessed by habituation and reactivity to novelty in the open field (OF) test, spatial memory in the Morris water maze (MWM), and the conditioned passive avoidance (PA) reflex. Basal serum corticosterone levels were assessed using an enzyme-linked immunosorbent assay. Results: Regardless of the housing conditions, females habituated to the OF under low illumination slower than males. Under bright light, the single-housed rats showed hyporeactivity to novelty. In the MWM, all the rats learned to locate the platform; however, on the first training day, the single-housed females’ speed was lower relative to other groups. Four months later, in the post-reminder probe trial, the single-housed rats reached the area around the platform site later, and only males, regardless of housing conditions, preferred the target quadrant. Single-housed rats, irrespective of sex, showed a PA deficit. There was a more pronounced conditioned fear in the single-housed males than in females. In both male and female rats, basal corticosterone levels in rat blood serum after 9 months of social isolation did not differ from that in the group-housed rats of the corresponding sex. Meanwhile, females’ basal corticosterone level was higher than in males, regardless of the housing conditions. The relative weight of the adrenal glands was increased only in single-housed females. Conclusions: Under long-term social isolation, started early in life, single-housed females compared with males showed more pronounced cognitive impairments in the MWM and PA paradigm, findings that specify their greater vulnerability to the stress of prolonged social isolation.

Altered synapsin I immunoreactivity and fear behavior in male and female rats subjected to long-term amygdala kindling

2009 ◽  
Vol 196 (1) ◽  
pp. 106-115 ◽  
Author(s):  
Neil M. Fournier ◽  
Andrea L. Darnbrough ◽  
Amanda J. Wintink ◽  
Lisa E. Kalynchuk
Keyword(s):  
Female Rats ◽  
Synapsin I ◽  
Male And Female ◽  
Male And Female Rats ◽  
Amygdala Kindling ◽  
Fear Behavior

scholarly journals Stress before Puberty Exerts a Sex- and Age-Related Impact on Auditory and Contextual Fear Conditioning in the Rat

2007 ◽  
Vol 2007 ◽  
pp. 1-12 ◽  
Author(s):  
Maria Toledo-Rodriguez ◽  
Carmen Sandi
Keyword(s):  
Fear Conditioning ◽  
Conditioned Fear ◽  
Early Adulthood ◽  
Contextual Fear Conditioning ◽  
Female Rats ◽  
Adult Males ◽  
Contextual Fear ◽  
Male And Female Rats ◽  
Age Related ◽  
The Impact

Adolescence is a period of major physical, hormonal, and psychological changes. It is also characterized by a significant increase in the incidence of psychopathologies and this increase is gender-specific. Stress during adolescence is associated with the development of psychiatric disorders later in life. In this study, we evaluated the impact of psychogenic stress (exposure to predator odor followed by placement on an elevated platform) experienced before puberty (days 28–30) on fear memories and hormonal response of male and female rats during adolescence and early adulthood. Stress before puberty impacted in a sex- and age-specific way on the responses to auditory and contextual fear conditioning in adolescence and adulthood: (a) increased conditioned fear to the tone in males during adolescence but not during adulthood; (b) impaired extinction to the tone in adult males; and (c) reduced freezing responses to the context in adolescent females. Stress before puberty did not influence the corticosterone levels 30 minutes after an additional stressor given in adulthood. These results indicate that stress experienced prior to puberty can exert a sex-related differential impact on fear-related behaviors displayed by individuals during late adolescence and early adulthood.

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