Individual variability in the recall of fear extinction is associated with phosphorylation of mitogen-activated protein kinase in the infralimbic cortex

Russo, Amanda S; Lee, Jessica; Parsons, Ryan G.

doi:10.1007/s00213-019-05195-2

Cited by 6 publications

(5 citation statements)

References 61 publications

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“…Imaging studies [21,49] have reported increased activity in BLA in animals recalling extinction memory. However, our prior work showed no difference in activation of the BLA in good versus poor extinction rats [7], and our results here show that extinction recall does not drive activation in the BLA broadly or within BLA projections to the IL. Consistent with our findings, whereas circuit manipulation studies indicate that IL inputs to the BLA are important for extinction learning [50,19], they are not necessary for extinction recall (Bukalo et al, 2016).…”

Section: Discussioncontrasting

confidence: 56%

“…Rodent models are useful in this endeavor because there is marked individual variation in extinction recall among rodents [5][6][7][8]. Prior work investigating the neural mechanisms of fear extinction at the group level has suggested that activation of the infralimbic cortex (IL) is necessary for extinction recall [9-11, but see 12], and a handful of studies have found reduced activity in the IL among rodents displaying poor extinction recall compared to rodents that extinguish fear well [13][14][15]7]. However, the mechanisms underlying the differential engagement of the IL in rodents that extinguish fear readily versus those that show poor extinction are not well understood.…”

Section: Introductionmentioning

confidence: 99%

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Neural Activity in Afferent Projections to the Infralimbic Cortex is Associated with Individual Differences in the Recall of Fear Extinction

Russo

Parsons

2022

Preprint

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Post-traumatic stress disorder (PTSD) is characterized by an impaired ability to extinguish fear responses to trauma-associated cues. Studies in humans and non-human animals point to differences in the engagement of certain frontal cortical regions as key mediators determining whether or not fear extinction is successful, however the neural circuit interactions that dictate the differential involvement of these regions are not well understood. To better understand how individual differences in extinction recall are reflected in differences in neural circuit activity, we labeled projections to the infralimbic cortex (IL) in rats using a retrograde tracer and compared neural activity within, and outside, of IL-projecting neurons. We analyzed these data in groups separated on the basis of how well rats retained extinction memory. We found that within IL-projecting cells, neurons in the posterior paraventricular thalamus showed heightened activity in rats that showed good extinction recall. Outside of the IL-projecting cells, increased Fos activity was observed in good extinction rats in select regions of the claustrum and ventral hippocampus. Our results indicate that differences in extinction recall are associated with a specific pattern of neural activity both within and outside of projections to the IL.

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Section: Discussioncontrasting

confidence: 56%

Section: Introductionmentioning

confidence: 99%

Neural Activity in Afferent Projections to the Infralimbic Cortex is Associated with Individual Differences in the Recall of Fear Extinction

Russo

Parsons

2022

Preprint

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“…All behavioral testing took place in four identical chambers (32 × 26 × 21 cm) (Clever Systems, Reston, VA) made of Plexiglas and stainless steel and housed in sound-attenuating boxes (Russo, Lee, & Parsons, 2019). During fear conditioning, a footshock was delivered through the floor which was composed of stainless-steel rods.…”

Section: Behavioral Testingmentioning

confidence: 99%

Gonadal hormone fluctuations do not affect the expression or extinction of fear-potentiated startle in female rats.

Voulo¹,

Parsons²

2019

Behavioral Neuroscience

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Prior studies suggest that levels of ovarian hormones may affect learning and memory in rats, including studies of fear conditioning and extinction. We previously showed that female rats show reduced retention of extinction compared to males when measuring fear-potentiated startle, but not when measuring freezing behavior. One commonly reported observation in studies of freezing behavior is that rats with increased levels of estradiol during extinction learning show better retention of extinction than rats given extinction training when levels of estradiol are low. Here, we tested the hypothesis that fear extinction retention in a fear-potentiated startle paradigm in females is influenced by levels gonadal hormones, which we had not accounted for in our original report. We used the fear-potentiated startle paradigm to test if extinction learning was affected by estrous phase, ovariectomy, or acute systemic injections of estradiol in ovariectomized rats. We report that neither the expression nor extinction of fear-potentiated startle differed in rats given extinction training in proestrus compared to those in metestrus. Removal of the ovaries had no effect on fear acquisition or extinction learning as assessed by fear-potentiated startle. Finally, systemic injections of estradiol given to ovariectomized rats before extinction training had no effect on the expression of fear or the retention of extinction. Our findings suggest that the effect of female gonadal hormones on fear conditioning and extinction may depend on the measure of fear employed or by the parameters used to study fear learning.

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“…The block of the first five tones during each extinction session was assessed to determine fear reduction level of the given day. Considering individual differences under fear conditioning [90][91][92] fear reduction during extinction was expressed as a fraction of the percentage of freezing expressed during the CS+ test (Day 3) (% Freezing Reduction = Freezing extinction × 100/Freezing test CS+). Fear remission was considered achieved when animals expressed <20% of the initial freezing during the first block of the day (i.e., first 5 CS+ presentations during the extinction session).…”

Section: Auditory Fear Conditioningmentioning

confidence: 99%

Closed-loop brain stimulation augments fear extinction in male rats

et al. 2023

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Dysregulated fear reactions can result from maladaptive processing of trauma-related memories. In post-traumatic stress disorder (PTSD) and other psychiatric disorders, dysfunctional extinction learning prevents discretization of trauma-related memory engrams and generalizes fear responses. Although PTSD may be viewed as a memory-based disorder, no approved treatments target pathological fear memory processing. Hippocampal sharp wave-ripples (SWRs) and concurrent neocortical oscillations are scaffolds to consolidate contextual memory, but their role during fear processing remains poorly understood. Here, we show that closed-loop, SWR triggered neuromodulation of the medial forebrain bundle (MFB) can enhance fear extinction consolidation in male rats. The modified fear memories became resistant to induced recall (i.e., ‘renewal’ and ‘reinstatement’) and did not reemerge spontaneously. These effects were mediated by D2 receptor signaling-induced synaptic remodeling in the basolateral amygdala. Our results demonstrate that SWR-triggered closed-loop stimulation of the MFB reward system enhances extinction of fearful memories and reducing fear expression across different contexts and preventing excessive and persistent fear responses. These findings highlight the potential of neuromodulation to augment extinction learning and provide a new avenue to develop treatments for anxiety disorders.

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Individual variability in the recall of fear extinction is associated with phosphorylation of mitogen-activated protein kinase in the infralimbic cortex

Cited by 6 publications

References 61 publications

Neural Activity in Afferent Projections to the Infralimbic Cortex is Associated with Individual Differences in the Recall of Fear Extinction

Neural Activity in Afferent Projections to the Infralimbic Cortex is Associated with Individual Differences in the Recall of Fear Extinction

Gonadal hormone fluctuations do not affect the expression or extinction of fear-potentiated startle in female rats.

Closed-loop brain stimulation augments fear extinction in male rats

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