scholarly journals Environmental enrichment prevents the late effect of acute stress-induced fear extinction deficit: the role of hippocampal AMPA-GluA1 phosphorylation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Leonardo Santana Novaes ◽  
Letícia Morais Bueno-de-Camargo ◽  
Carolina Demarchi Munhoz
Keyword(s):  
Environmental Enrichment ◽  
Basolateral Amygdala ◽  
Acute Stress ◽  
Fear Memory ◽  
Fear Extinction ◽  
Post Traumatic Stress ◽  
Related Disorder ◽  
Memory Extinction ◽  
Post Traumatic

AbstractThe persistence of anxiety and the deficit of fear memory extinction are both phenomena related to the symptoms of a trauma-related disorder, such as post-traumatic stress disorder (PTSD). Recently we have shown that single acute restraint stress (2 h) in rats induces a late anxiety-related behavior (observed ten days after stress), whereas, in the present work, we found that the same stress impaired fear extinction in animals conditioned ten days after stress. Fourteen days of environmental enrichment (EE) prevented the deleterious effect of stress on fear memory extinction. Additionally, we observed that EE prevented the stress-induced increase in AMPA receptor GluA1 subunit phosphorylation in the hippocampus, but not in the basolateral amygdala complex and the frontal cortex, indicating a potential mechanism by which it exerts its protective effect against the stress-induced behavioral outcome.

scholarly journals Amygdalar CB2 cannabinoid receptor mediates fear extinction deficits promoted by orexin-A/hypocretin-1

2021 ◽  
Author(s):  
Marc Ten-Blanco ◽  
África Flores ◽  
Inmaculada Pereda-Pérez ◽  
Fabiana Piscitelli ◽  
Cristina Izquierdo-Luengo ◽  
...  
Keyword(s):  
Basolateral Amygdala ◽  
Cannabinoid Receptor ◽  
Fear Extinction ◽  
Post Traumatic Stress ◽  
Orexin A ◽  
Post Traumatic ◽  
Learned Fear ◽  
Endogenous Cannabinoid ◽  
Endogenous Cannabinoid System

Background and purpose: Anxiety is often characterized by an inability to extinguish learned fear responses. Orexins/hypocretins are involved in the modulation of aversive memories, and dysregulation of this system may contribute to the aetiology of anxiety disorders characterized by pathological fear. The mechanisms by which orexins regulate fear remain unknown. Experimental approach: We investigated the role of the endogenous cannabinoid system in the impaired fear extinction induced by orexin-A (OXA) in male mice. Behavioural pharmacology, neurochemical, molecular and genetic approaches were used. Key results: The selective inhibitor of 2-arachidonoylglycerol (2-AG) biosynthesis O7460 abolished the fear extinction deficits induced by OXA. Accordingly, increased 2-AG levels were observed in the amygdala and hippocampus of mice treated with OXA that do not extinguish fear, suggesting that high levels of this endocannabinoid are related to poor extinction. Impairment of fear extinction induced by OXA was associated with increased expression of CB2 cannabinoid receptor (CB2R) in microglial cells of the basolateral amygdala. Consistently, the intra-amygdala infusion of the CB2R antagonist AM630 completely blocked the impaired extinction promoted by OXA. Microglial and CB2R expression depletion in the amygdala with PLX5622 chow also prevented these extinction deficits. Conclusions and implications: We reveal that overactivation of the orexin system leads to impaired fear extinction through 2-AG and amygdalar CB2R. This novel mechanism may pave the way towards novel potential approaches to treat diseases associated with inappropriate retention of fear, such as post-traumatic stress disorder, panic anxiety and phobias.

scholarly journals Role of Amygdala-Infralimbic Cortex Circuitry in Glucocorticoid-Induced Facilitation of Auditory Fear Memory Extinction

2021 ◽  
pp. 1-22
Author(s):  
Masoomeh Dadkhah ◽  
◽  
Abbas Ali Vafaei ◽  
Ali Rashidy-Pour ◽  
Parnia Trahomi ◽  
...  
Keyword(s):  
Critical Role ◽  
Fear Memory ◽  
Fear Extinction ◽  
Freezing Behavior ◽  
Extinction Training ◽  
Male Rats ◽  
Memory Extinction ◽  
The Right ◽  
Fear Expression

Purpose: The basolateral amygdala (BLA) and infralimbic area (IL) of medial prefrontal cortex (mPFC) are two inter-connected brain structures that mediate both fear memory expression and extinction. Besides the well-known role of the BLA in the acquisition and expression of fear memory, projections from IL to BLA inhibit fear expression and have a critical role in fear extinction. However, the details of IL-BLA interaction remain unclear. Here, we aimed to investigate the role of functional reciprocal interactions between BLA and IL in mediating fear memory extinction. Methods: Using lidocaine (LID), male rats underwent unilateral or bilateral inactivation of the BLA and then unilateral intra-IL infusion of CORT, prior to extinction training of auditory fear conditioning paradigm. Freezing behavior was reported as an index for the measurement of conditioned fear. Infusions were performed before the extinction training, allowing to examine the effects on fear expression and also further extinction memory. Experiments 1-3 investigated the effects of left or right infusion of CORT into IL, and LID unilaterally into BLA on fear memory extinction. Results: Results showed that intra-IL infusion of CORT in the right hemisphere reduced freezing behavior when administrated before the extinction training. Auditory fear memory extinction was impaired by asymmetric inactivation of BLA and CORT infusion in the right IL; however, the same effect was not observed with symmetric inactivation of BLA. Conclusion: It is concluded that that the IL-BLA neural circuit may provide additional evidence to contribution of this circuit in auditory fear extinction. This study demonstrate dissociable roles for right or left BLA in subserving the auditory fear extinction. Our finding also raise the possibility that left BLA-IL circuitry may contribute in mediating auditory fear memory extinction via underlying mechanisms, however further research is required.

The Role of Perceived Authenticity in Psychological Recovery from Collective Trauma

2020 ◽  
Vol 39 (5) ◽  
pp. 419-448
Author(s):  
Joseph Maffly-Kipp ◽  
Patricia Flanagan ◽  
Jinhyung Kim ◽  
Rebecca J. Schlegel ◽  
Matthew Vess ◽  
...  
Keyword(s):  
Psychological Health ◽  
Acute Stress ◽  
Multilevel Modelling ◽  
Collective Trauma ◽  
Post Traumatic Stress ◽  
The Face ◽  
Post Traumatic ◽  
And Coping ◽  
Insight Into

Introduction: Previous research demonstrates that perceived authenticity is positively associated with psychological health and security in the face of threats. The current research extends this work by testing whether perceived authenticity promotes recovery from the negative mental health consequences of collective trauma (e.g., a natural disaster). Methods: We recruited a sample of undergraduates (N = 570), many of whom reported direct or indirect exposure to Hurricane Harvey, to complete surveys at two time points. We assessed exposure to the disaster, acute stress, post-traumatic stress, coping, and authenticity twice, once approximately 1 month after Hurricane Harvey (Time 1) and again approximately 9 weeks after Hurricane Harvey (Time 2). Results: We employed multilevel modelling to explore whether authenticity would aid in recovery from collective trauma. Results showed that perceived authentic living at Time 1 predicted a variety of indicators of stress related to the hurricane at Time 2. Specifically, those participants who reported low authentic living at Time 1 reported greater levels of stress at Time 2, compared to individuals who reported higher levels of authentic living. Importantly, these effects remained even when controlling for known predictors of stress (e.g., levels of stress at Time 1 and coping strategies). Discussion: Findings provide preliminary insight into authenticity as a part of a likely larger network of interrelated psychosocial qualities that have the potential to help one navigate recovery from trauma.

scholarly journals Oxytocin and Fear Memory Extinction: Possible Implications for the Therapy of Fear Disorders?

2021 ◽  
Vol 22 (18) ◽  
pp. 10000
Author(s):  
Elisabetta Baldi ◽  
Alessia Costa ◽  
Barbara Rani ◽  
Maria Beatrice Passani ◽  
Patrizio Blandina ◽  
...  
Keyword(s):  
Conditioned Fear ◽  
Brain Structures ◽  
Brain Regions ◽  
Fear Extinction ◽  
Post Traumatic Stress ◽  
Pharmacological Agents ◽  
Memory Extinction ◽  
Post Traumatic ◽  
Psychiatric Conditions ◽  
Fear And Anxiety

Several psychiatric conditions such as phobias, generalized anxiety, and post-traumatic stress disorder (PTSD) are characterized by pathological fear and anxiety. The main therapeutic approach used in the management of these disorders is exposure-based therapy, which is conceptually based upon fear extinction with the formation of a new safe memory association, allowing the reduction in behavioral conditioned fear responses. Nevertheless, this approach is only partially resolutive, since many patients have difficulty following the demanding and long process, and relapses are frequently observed over time. One strategy to improve the efficacy of the cognitive therapy is the combination with pharmacological agents. Therefore, the identification of compounds able to strengthen the formation and persistence of the inhibitory associations is a key goal. Recently, growing interest has been aroused by the neuropeptide oxytocin (OXT), which has been shown to have anxiolytic effects. Furthermore, OXT receptors and binding sites have been found in the critical brain structures involved in fear extinction. In this review, the recent literature addressing the complex effects of OXT on fear extinction at preclinical and clinical levels is discussed. These studies suggest that the OXT roles in fear behavior are due to its local effects in several brain regions, most notably, distinct amygdaloid regions.

scholarly journals Amygdala Reward Neurons Form and Store Fear Extinction Memory

2019 ◽  
Author(s):  
Xiangyu Zhang ◽  
Joshua Kim ◽  
Susumu Tonegawa
Keyword(s):  
Emotional Disorders ◽  
Basolateral Amygdala ◽  
Conditioned Fear ◽  
Fear Memory ◽  
Fear Extinction ◽  
Neuronal Population ◽  
Post Traumatic Stress ◽  
Extinction Memory ◽  
Memory Engram ◽  
Reward Behaviors

SummaryThe ability to extinguish conditioned fear memory is critical for adaptive control of fear response, and its impairment is a hallmark of emotional disorders like post-traumatic stress disorder (PTSD). Fear extinction is thought to take place when animals form a new memory that suppresses the original fear memory. However, little is known about the nature and the site of formation and storage of the new extinction memory. Here, we demonstrate that a fear extinction memory engram is formed and stored in a genetically distinct basolateral amygdala (BLA) neuronal population that drive reward behaviors and antagonize the BLA’s original fear neurons. The activation of the fear extinction engram neurons and natural reward-responsive neurons overlap extensively in the BLA. Furthermore, these two neuron subsets are mutually interchangeable in driving reward behaviors and fear extinction behaviors. Thus, fear extinction memory is a newly formed reward memory.

scholarly journals The Role of HPA Axis and Allopregnanolone on the Neurobiology of Major Depressive Disorders and PTSD

2021 ◽  
Vol 22 (11) ◽  
pp. 5495
Author(s):  
Felipe Borges Almeida ◽  
Graziano Pinna ◽  
Helena Maria Tannhauser Barros
Keyword(s):  
Hpa Axis ◽  
Depressive Disorders ◽  
Post Traumatic Stress ◽  
Major Depressive ◽  
Physiological Adaptations ◽  
Suppression Test ◽  
Post Traumatic ◽  
Major Depressive Disorders ◽  
Cortisol Release

Under stressful conditions, the hypothalamic-pituitary-adrenal (HPA) axis acts to promote transitory physiological adaptations that are often resolved after the stressful stimulus is no longer present. In addition to corticosteroids (e.g., cortisol), the neurosteroid allopregnanolone (3α,5α-tetrahydroprogesterone, 3α-hydroxy-5α-pregnan-20-one) participates in negative feedback mechanisms that restore homeostasis. Chronic, repeated exposure to stress impairs the responsivity of the HPA axis and dampens allopregnanolone levels, participating in the etiopathology of psychiatric disorders, such as major depressive disorder (MDD) and post-traumatic stress disorder (PTSD). MDD and PTSD patients present abnormalities in the HPA axis regulation, such as altered cortisol levels or failure to suppress cortisol release in the dexamethasone suppression test. Herein, we review the neurophysiological role of allopregnanolone both as a potent and positive GABAergic neuromodulator but also in its capacity of inhibiting the HPA axis. The allopregnanolone function in the mechanisms that recapitulate stress-induced pathophysiology, including MDD and PTSD, and its potential as both a treatment target and as a biomarker for these disorders is discussed.

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