Unrelenting Fear Under Stress: Neural Circuits and Mechanisms for the Immediate Extinction Deficit
Therapeutic interventions for disorders of fear and anxiety rely on behavioral approaches that reduce pathological fear memories. For example, learning that threat-predictive stimuli are no longer associated with aversive outcomes is central to the extinction of conditioned fear responses. Unfortuna...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-04-01
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| Series: | Frontiers in Systems Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnsys.2022.888461/full |
| _version_ | 1811300296312225792 |
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| author | Stephen Maren |
| author_facet | Stephen Maren |
| author_sort | Stephen Maren |
| collection | DOAJ |
| description | Therapeutic interventions for disorders of fear and anxiety rely on behavioral approaches that reduce pathological fear memories. For example, learning that threat-predictive stimuli are no longer associated with aversive outcomes is central to the extinction of conditioned fear responses. Unfortunately, fear memories are durable, long-lasting, and resistant to extinction, particularly under high levels of stress. This is illustrated by the “immediate extinction deficit,” which is characterized by a poor long-term reduction of conditioned fear when extinction procedures are attempted within hours of fear conditioning. Here, I will review recent work that has provided new insight into the neural mechanisms underlying resistance to fear extinction. Emerging studies reveal that locus coeruleus norepinephrine modulates amygdala-prefrontal cortical circuits that are critical for extinction learning. These data suggest that stress-induced activation of brain neuromodulatory systems biases fear memory at the expense of extinction learning. Behavioral and pharmacological strategies to reduce stress in patients undergoing exposure therapy might improve therapeutic outcomes. |
| first_indexed | 2024-04-13T06:48:57Z |
| format | Article |
| id | doaj.art-f43a777976a34ce9bbe810bd2e8bbc79 |
| institution | Directory Open Access Journal |
| issn | 1662-5137 |
| language | English |
| last_indexed | 2024-04-13T06:48:57Z |
| publishDate | 2022-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Systems Neuroscience |
| spelling | doaj.art-f43a777976a34ce9bbe810bd2e8bbc792022-12-22T02:57:28ZengFrontiers Media S.A.Frontiers in Systems Neuroscience1662-51372022-04-011610.3389/fnsys.2022.888461888461Unrelenting Fear Under Stress: Neural Circuits and Mechanisms for the Immediate Extinction DeficitStephen MarenTherapeutic interventions for disorders of fear and anxiety rely on behavioral approaches that reduce pathological fear memories. For example, learning that threat-predictive stimuli are no longer associated with aversive outcomes is central to the extinction of conditioned fear responses. Unfortunately, fear memories are durable, long-lasting, and resistant to extinction, particularly under high levels of stress. This is illustrated by the “immediate extinction deficit,” which is characterized by a poor long-term reduction of conditioned fear when extinction procedures are attempted within hours of fear conditioning. Here, I will review recent work that has provided new insight into the neural mechanisms underlying resistance to fear extinction. Emerging studies reveal that locus coeruleus norepinephrine modulates amygdala-prefrontal cortical circuits that are critical for extinction learning. These data suggest that stress-induced activation of brain neuromodulatory systems biases fear memory at the expense of extinction learning. Behavioral and pharmacological strategies to reduce stress in patients undergoing exposure therapy might improve therapeutic outcomes.https://www.frontiersin.org/articles/10.3389/fnsys.2022.888461/fullextinctionstressfear conditioningnorepinephrinelocus coeruleusamygdala |
| spellingShingle | Stephen Maren Unrelenting Fear Under Stress: Neural Circuits and Mechanisms for the Immediate Extinction Deficit Frontiers in Systems Neuroscience extinction stress fear conditioning norepinephrine locus coeruleus amygdala |
| title | Unrelenting Fear Under Stress: Neural Circuits and Mechanisms for the Immediate Extinction Deficit |
| title_full | Unrelenting Fear Under Stress: Neural Circuits and Mechanisms for the Immediate Extinction Deficit |
| title_fullStr | Unrelenting Fear Under Stress: Neural Circuits and Mechanisms for the Immediate Extinction Deficit |
| title_full_unstemmed | Unrelenting Fear Under Stress: Neural Circuits and Mechanisms for the Immediate Extinction Deficit |
| title_short | Unrelenting Fear Under Stress: Neural Circuits and Mechanisms for the Immediate Extinction Deficit |
| title_sort | unrelenting fear under stress neural circuits and mechanisms for the immediate extinction deficit |
| topic | extinction stress fear conditioning norepinephrine locus coeruleus amygdala |
| url | https://www.frontiersin.org/articles/10.3389/fnsys.2022.888461/full |
| work_keys_str_mv | AT stephenmaren unrelentingfearunderstressneuralcircuitsandmechanismsfortheimmediateextinctiondeficit |