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Fear extinction

Xiao-Lin Chou, Xiyue Wang, Zheng-Gang Zhang, Li Shen, Brian Zingg, Junxiang Huang, Wen Zhong, Lukas Mesik, Li I Zhang, Huizhong Whit Tao
Zona incerta (ZI) is a functionally mysterious subthalamic nucleus containing mostly inhibitory neurons. Here, we discover that GABAergic neurons in the rostral sector of ZI (ZIr) directly innervate excitatory but not inhibitory neurons in the dorsolateral and ventrolateral compartments of periaqueductal gray (PAG), which can drive flight and freezing behaviors respectively. Optogenetic activation of ZIr neurons or their projections to PAG reduces both sound-induced innate flight response and conditioned freezing response, while optogenetic suppression of these neurons enhances these defensive behaviors, likely through a mechanism of gain modulation...
March 20, 2018: Nature Communications
Shuhua Lai, Gangwei Wu, Zhixian Jiang
BACKGROUND/AIMS: Impaired fear memory extinction is widely considered a key mechanism of post-traumatic stress disorder (PTSD). Recent studies have suggested that neuroinflammation after a single prolonged stress (SPS) exposure may play a critical role in the impaired fear memory extinction. Studies have shown that high mobility group box chromosomal protein 1 (HMGB-1) is critically involved in neuroinflammation. However, the role of HMGB-1 underlying the development of impairment of fear memory extinction is still not known...
March 16, 2018: Cellular Physiology and Biochemistry
Chu-Chu Qi, Qing-Jun Wang, Xue-Zhu Ma, Hai-Chao Chen, Li-Ping Gao, Jie Yin, Yu-Hong Jing
BACKGROUND: Following a social defeat, the balanced establishment and extinction of aversive information is a beneficial strategy for individual survival. Abnormal establishment or extinction is implicated in the development of mental disorders. This study investigated the time course of the establishment and extinction of aversive information from acute social defeat and the temporal responsiveness of the basolateral amygdala (BLA), ventral hippocampus (vHIP) and medial prefrontal cortex (mPFC) in this process...
March 19, 2018: Behavioral and Brain Functions: BBF
Rheall F Roquet, Dong-Oh Seo, Carolyn E Jones, Marie-H Monfils
We examined the enduring effects of predictable versus unpredictable fear conditioning early in life on memory and relearning in adulthood. At postnatal Day 17 or 25 (P17 or P25), rats either remained naïve, or were fear conditioned using paired (predictable) or unpaired (unpredictable) presentations of white noise and foot shocks. At 2 months of age (adulthood), each group was fear conditioned (or reconditioned) with either paired or unpaired training, and then was tested for fear extinction the next day...
February 2018: Behavioral Neuroscience
Rohit Menon, Thomas Grund, Iulia Zoicas, Ferdinand Althammer, Dominik Fiedler, Verena Biermeier, Oliver J Bosch, Yuichi Hiraoka, Katsuhiko Nishimori, Marina Eliava, Valery Grinevich, Inga D Neumann
Oxytocin (OXT)-mediated behavioral responses to social and stressful cues have extensively been studied in male rodents. Here, we investigated the capacity of brain OXT receptor (OXTR) signaling in the lateral septum (LS) to prevent social fear expression in female mice using the social-fear-conditioning paradigm. Utilizing the activated OXT system during lactation, we show that lactating mice did not express fear 24 hr after social fear conditioning. Supporting the role of OXTR signaling in the LS in attenuation of social fear, synthetic OXT infusion or overexpression of OXTR in the LS diminished social fear expression, whereas constitutive OXTR knockout severely impaired social fear extinction in virgin mice...
March 7, 2018: Current Biology: CB
Kim L Felmingham, Daniel V Zuj, Ken Chia Ming Hsu, Emma Nicholson, Matthew A Palmer, Kimberley Stuart, James C Vickers, Gin S Malhi, Richard A Bryant
The low expression Met allele of the BDNF Val66Met polymorphism is associated with impaired fear extinction in healthy controls, and poorer response to exposure therapy in patients with Posttraumatic Stress Disorder (PTSD). Given that fear extinction underlies exposure therapy, this raises the question of the impact of BDNFVal66Met polymorphism on fear extinction in PTSD, yet this question has not yet been examined. One hundred and six participants (22 PTSD, 46 trauma-exposed controls (TC) and 38 non-trauma exposed controls (NTC)) completed a fear conditioning and extinction task and saliva samples were taken for DNA extraction and genotyped for the BDNF Val66Met polymorphism...
March 6, 2018: Psychoneuroendocrinology
Andre Pittig, Michael Treanor, Richard T LeBeau, Michelle G Craske
Anxiety disorders are the most common mental disorders, and are often chronic and disabling. Although exposure-based treatments are effective, a substantial number of individuals fail to fully remit or experience a return of symptoms after treatment. Understanding the critical processes underlying the development and treatment of anxiety disorders will help identify individuals at risk and optimize treatments. Aversive associative learning offers explanatory pathways through which fear and anxiety emerge, spread, persist, and resurge...
March 14, 2018: Neuroscience and Biobehavioral Reviews
Karina R O'Malley, Allison M Waters
Exposure therapy is a key component of efficacious treatment for anxiety. Biases in the allocation of attention towards versus away from threat assessed prior to exposure-based treatments such as cognitive-behavioural therapy differentially predict treatment outcomes. However, it is unclear whether monitoring versus avoiding threat stimuli influences learning during exposure. Extinction paradigms are the experimental analogue of exposure therapy. Therefore, manipulating attention towards versus away from threat during extinction trials may shed light on the role of attention during exposure therapy...
March 6, 2018: Behaviour Research and Therapy
Mariana Fortunata Donadon, Rocio Martin-Santos, Flávia de Lima Osório
Studies have shown that traumatic experiences may affect hormonal systems mediated by the hypothalamic-pituitary-adrenal (HPA) axis and the oxytocinergic system. This effect is the result of long-term impairments in hypothalamic structures and negative feedback mechanisms within the HPA axis, structures that mediate the response to stress. This deregulation reduces the production and release of cortisol and oxytocin (OXT), which may alter stress responses and lead to increased vulnerability to impairments from stressful experiences...
2018: Frontiers in Pharmacology
Madelyne A Bisby, Kathryn D Baker, Rick Richardson
NMDA receptors (NMDARs) are considered critical for the consolidation of extinction but recent work challenges this assumption. Namely, NMDARs are not required for extinction retention in infant rats as well as when extinction training occurs for a second time (i.e., reextinction) in adult rats. In this study, a possible third instance of NMDAR-independent extinction was tested. Although adolescents typically exhibit impaired extinction retention, rats that are conditioned as juveniles and then given extinction training as adolescents (JuvCond-AdolesExt) have good extinction retention...
April 2018: Learning & Memory
Vipan K Parihar, Mattia Maroso, Amber Syage, Barrett D Allen, Maria C Angulo, Ivan Soltesz, Charles L Limoli
Of the many perils associated with deep space travel to Mars, neurocognitive complications associated with cosmic radiation exposure are of particular concern. Despite these realizations, whether and how realistic doses of cosmic radiation cause cognitive deficits and neuronal circuitry alterations several months after exposure remains unclear. In addition, even less is known about the temporal progression of cosmic radiation-induced changes transpiring over the duration of a time period commensurate with a flight to Mars...
March 11, 2018: Experimental Neurology
Shingo Matsuda, Daisuke Matsuzawa, Daisuke Ishii, Haruna Tomizawa, Eiji Shimizu
Onset of fear-related disorders such as post-traumatic stress disorder is enhanced from adolescence until adulthood. However, the biological mechanisms underlying this vulnerability remain unclear. Therefore, we investigated contextual fear memory and extinction in 4-, 6-, 8-, 10-, and 15-week-old female mice. We also measured phosphorylation of ERK2 in the medial prefrontal cortex (mPFC) and the dorsal hippocampus in the mPFC following fear conditioning or extinction in 6- and 15-week-old mice. We found that 10- and 15-week-old mice showed stronger fear memory and more resistance to fear extinction than 6-week-old mice...
March 10, 2018: Neurobiology of Learning and Memory
Miquel A Fullana, Anton Albajes-Eizagirre, Carles Soriano-Mas, Bram Vervliet, Narcís Cardoner, Olívia Benet, Joaquim Radua, Ben J Harrison
The study of fear extinction represents an important example of translational neuroscience in psychiatry and promises to improve the understanding and treatment of anxiety and fear-related disorders. We present the results of a set of meta-analyses of human fear extinction studies in healthy participants, conducted with functional magnetic resonance imaging (fMRI) and reporting whole-brain results. Meta-analyses of fear extinction learning primarily implicate consistent activation of brain regions linked to threat appraisal and experience, including the dorsal anterior cingulate and anterior insular cortices...
March 9, 2018: Neuroscience and Biobehavioral Reviews
Ki Eun Shin, Michelle G Newman
Even after successful exposure, relapse is not uncommon. Based on the retrieval model of fear extinction (e.g., Vervliet, Craske, & Hermans, 2013), return of fear can occur after exposure due to an elapse of time (spontaneous recovery) or change in context (contextual renewal). The use of external salient stimuli presented throughout extinction (i.e., retrieval cues [RCs]) has been suggested as a potential solution to this problem (Bouton, 2002). The current study examined whether RCs attenuated return of fear in individuals with public speaking anxiety...
March 2018: Behavior Therapy
Valerie L Kinner, Oliver T Wolf, Christian J Merz
Relapses represent a major limitation to the long-term remission of pathological fear and anxiety. Stress modulates the acquisition and expression of fear memories and appears to promote fear recovery in patients with anxiety disorders. However, the neural correlates underlying stress hormone effects on the return of fear in humans remain unexplored. Likewise, little is known about the interactions between sex and stress hormones on return of fear phenomena. In this functional magnetic resonance imaging study, 32 men and 32 women were exposed to a fear renewal paradigm with fear acquisition in context A and extinction in context B...
February 21, 2018: Psychoneuroendocrinology
Allison A Feduccia, Michael C Mithoefer
MDMA-assisted psychotherapy for treatment of PTSD has recently progressed to Phase 3 clinical trials and received Breakthrough Therapy designation by the FDA. MDMA used as an adjunct during psychotherapy sessions has demonstrated effectiveness and acceptable safety in reducing PTSD symptoms in Phase 2 trials, with durable remission of PTSD diagnosis in 68% of participants. The underlying psychological and neurological mechanisms for the robust effects in mitigating PTSD are being investigated in animal models and in studies of healthy volunteers...
March 7, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
Sharon Fidelman, Tomer Mizrachi Zer-Aviv, Rachel Lange, Cecilia J Hillard, Irit Akirav
Activating the endocannabinoid system has become a major focus in the search for novel therapeutics for anxiety and deficits in fear extinction, two defining features of PTSD. We examined whether chronic treatment with the fatty acid amide hydrolase (FAAH) inhibitor URB597 (0.2, 0.3, 0.4 mg/kg, i.p.) or the CB1/2 receptor agonist WIN55,212-2 (0.25, 0.5 mg/kg, i.p.) injected for 3 weeks to rats exposed to the shock and reminders model of PTSD would attenuate post-stress symptoms and affect basolateral amygdala (BLA) and CA1 CB1 receptors...
March 5, 2018: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
Nura W Lingawi, Nathan M Holmes, R Fredrick Westbrook, Vincent Laurent
Evidence indicates that the infralimbic cortex (IL) encodes and retrieves the inhibitory memory produced by fear extinction. Recently, we have shown that the IL is also involved in the inhibitory memory generated by stimulus pre-exposure that causes latent inhibition. These results are surprising because a stimulus undergoing fear extinction carries aversive motivational value, whereas a pre-exposed stimulus is neutral. The present experiments tested the hypothesis that the IL encodes inhibition irrespective of the motivational information about the stimulus...
March 5, 2018: Neurobiology of Learning and Memory
Daniel W Bloodgood, Jonathan A Sugam, Andrew Holmes, Thomas L Kash
Fear extinction involves the formation of a new memory trace that attenuates fear responses to a conditioned aversive memory, and extinction impairments are implicated in trauma- and stress-related disorders. Previous studies in rodents have found that the infralimbic prefrontal cortex (IL) and its glutamatergic projections to the basolateral amygdala (BLA) and basomedial amygdala (BMA) instruct the formation of fear extinction memories. However, it is unclear whether these pathways are exclusively involved in extinction, or whether other major targets of the IL, such as the nucleus accumbens (NAc) also play a role...
March 6, 2018: Translational Psychiatry
Laurie L Wellman, Mairen E Fitzpatrick, Amy M Sutton, Brook L Williams, Mayumi Machida, Larry D Sanford
The basolateral nucleus of the amygdala (BLA) plays a significant role in mediating individual differences in the effects of fear memory on sleep. Here, we assessed the effects of antagonizing corticotropin releasing factor receptor 1 (CRFR1) after shock training (ST) on fear-conditioned behaviors and sleep. Outbred Wistar rats were surgically implanted with electrodes for recording EEG and EMG and with bilateral guide cannulae directed at BLA. Data loggers were placed intraperitoneally to record core body temperature...
March 1, 2018: Hormones and Behavior
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