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Fear extinction

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https://www.readbyqxmd.com/read/28097489/enhanced-histone-acetylation-in-the-infralimbic-prefrontal-cortex-is-associated-with-fear-extinction
#1
Sarfraj Ahmad Siddiqui, Sanjay Singh, Vandana Ranjan, Rajesh Ugale, Sudipta Saha, Anand Prakash
The molecular processes that establish fear memory are complex and involve a combination of genetic and epigenetic influences. Dysregulation of these processes can manifest in humans as a range of fear-related anxiety disorders like post-traumatic stress disorders (PTSD). In the present study, immunohistochemistry for acetyl H3, H4, c-fos, CBP (CREB-binding protein) in the infralimbic prefrontal cortex (IL-PFC) and prelimbic prefrontal cortex (PL-PFC) of mPFC (medial prefrontal cortex) and basal amygdala (BA), lateral amygdala (LA), centrolateral amygdala (CeL), centromedial amygdala (CeM) of the amygdala was performed to link region-specific histone acetylation to fear and extinction learning...
January 17, 2017: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/28071689/haploinsufficiency-of-ehmt1-improves-pattern-separation-and-increases-hippocampal-cell-proliferation
#2
Marco Benevento, Charlotte A Oomen, Alexa E Horner, Houshang Amiri, Tessa Jacobs, Charlotte Pauwels, Monica Frega, Tjitske Kleefstra, Maksym V Kopanitsa, Seth G N Grant, Timothy J Bussey, Lisa M Saksida, Catharina E E M Van der Zee, Hans van Bokhoven, Jeffrey C Glennon, Nael Nadif Kasri
Heterozygous mutations or deletions of the human Euchromatin Histone Methyltransferase 1 (EHMT1) gene are the main causes of Kleefstra syndrome, a neurodevelopmental disorder that is characterized by impaired memory, autistic features and mostly severe intellectual disability. Previously, Ehmt1(+/-) heterozygous knockout mice were found to exhibit cranial abnormalities and decreased sociability, phenotypes similar to those observed in Kleefstra syndrome patients. In addition, Ehmt1(+/-) knockout mice were impaired at fear extinction and novel- and spatial object recognition...
January 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28067903/modulation-of-excitation-on-parvalbumin-interneurons-by-neuroligin-3-regulates-the-hippocampal-network
#3
Jai S Polepalli, Hemmings Wu, Debanjan Goswami, Casey H Halpern, Thomas C Südhof, Robert C Malenka
Hippocampal network activity is generated by a complex interplay between excitatory pyramidal cells and inhibitory interneurons. Although much is known about the molecular properties of excitatory synapses on pyramidal cells, comparatively little is known about excitatory synapses on interneurons. Here we show that conditional deletion of the postsynaptic cell adhesion molecule neuroligin-3 in parvalbumin interneurons causes a decrease in NMDA-receptor-mediated postsynaptic currents and an increase in presynaptic glutamate release probability by selectively impairing the inhibition of glutamate release by presynaptic Group III metabotropic glutamate receptors...
January 9, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28065842/fear-extinction-and-memory-reconsolidation-as-critical-components-in-behavioral-treatment-for-posttraumatic-stress-disorder-and-potential-augmentation-of-these-processes
#4
REVIEW
Noelle B Smith, Jennifer M Doran, Lauren M Sippel, Ilan Harpaz-Rotem
Posttraumatic stress disorder (PTSD) is associated with alterations in critical brain regions such as the amygdala, hippocampus, and prefrontal cortex. This brief review has two objectives: (1) to discuss research examining extinction and reconsolidation processes as mechanisms in PTSD psychotherapy, and (2) present possibilities for augmenting extinction and reconsolidation within treatment through alterations to therapeutic interventions and novel approaches. A key component of many effective PTSD therapies is exposure, which involves intentional confrontation and processing of the traumatic memory...
January 5, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28062924/memory-formation-orchestrates-the-wiring-of-adult-born-hippocampal-neurons-into-brain-circuits
#5
Petnoi Petsophonsakul, Kevin Richetin, Trinovita Andraini, Laurent Roybon, Claire Rampon
During memory formation, structural rearrangements of dendritic spines provide a mean to durably modulate synaptic connectivity within neuronal networks. New neurons generated throughout the adult life in the dentate gyrus of the hippocampus contribute to learning and memory. As these neurons become incorporated into the network, they generate huge numbers of new connections that modify hippocampal circuitry and functioning. However, it is yet unclear as to how the dynamic process of memory formation influences their synaptic integration into neuronal circuits...
January 6, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/28061973/the-melatonergic-system-in-anxiety-disorders-and-the-role-of-melatonin-in-conditional-fear
#6
F Huang, Z Yang, C-Q Li
BACKGROUND: Resistance to extinction of certain conditioned responses forms the basis of anxieties, phobias, and compulsions. There has been an available effective means of extinction-based exposure psychotherapy for the treatment of anxiety disorders, such as posttraumatic stress disorder (PTSD) that has been hypothesized to result from impaired extinction of fear memory. PTSD is considered as a memory disorder within a Pavlovian fear conditioning and extinction framework. Therefore, the aim of this review was to report the preclinical profile of melatonin, a pineal gland hormone, as a potential pharmacological option in the treatment of anxiety disorders such as PTSD, tested with the Pavlovian fear conditioning paradigm...
2017: Vitamins and Hormones
https://www.readbyqxmd.com/read/28057529/genetic-inhibition-of-anaplastic-lymphoma-kinase-rescues-cognitive-impairments-in-neurofibromatosis-1-mutant-mice
#7
Joseph B Weiss, Sydney J Weber, Eileen Ruth S Torres, Tessa Marzulla, Jacob Raber
Heterozygous Neurofibromatosis 1 (NF1) loss of function mutations occur in approximately 90% of patients with neurofibromatosis. A major, disabling phenotypic consequence of reduced NF1 function is cognitive impairment; a possibly related behavioral phenotype is impaired sleep. Recent results in Drosophila have demonstrated a genetic interaction between Anaplastic Lymphoma Kinase (Alk) and NF1 for both associative learning and sleep. Inhibition of Alk improves associative learning and sleep in heterozygous NF1 mutant flies...
January 3, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28055142/executive-functions-deficits-impair-extinction-of-generalization-of-fear-of-movement-related-pain
#8
N G Niederstrasser, A Meulders, M Meulders, D Struyf, J W Vlaeyen
BACKGROUND: Generalization of fear of movement-related pain across novel but similar movements can lead to fear responses to movements that are actually not associated with pain. The peak-shift effect describes a phenomenon whereby particular novel movements elicit even greater fear responses than the original pain-provoking movement (CS+), because they represent a more extreme version of the CS+. There is great variance in the propensity to generalize as well as the speed of extinction learning when these novel movements are not followed by pain...
January 5, 2017: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/28045462/hippocampal-encoding-of-interoceptive-context-during-fear-conditioning
#9
S-W Yoo, M Bae, L B Tovar-Y-Romo, N J Haughey
Rodent models of auditory fear conditioning are often used to understand the molecular mechanisms regulating fear- and anxiety-related behaviors. Conditioning and extinction memories are influenced by contextual cues, and the reinstatement of conditioned fear occurs when the conditioning stimulus is presented in a context different from the extinction context. Although it has been proposed that internal state is a feature of context that could influence extinction, contributions of interoception to conditioning have not been experimentally addressed...
January 3, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28043916/ketamine-accelerates-fear-extinction-via-mtorc1-signaling
#10
Matthew J Girgenti, Sriparna Ghosal, Dora LoPresto, Jane R Taylor, Ronald S Duman
Impaired fear extinction contributes to the persistence of post-traumatic stress disorder (PTSD), and can be utilized for the study of novel therapeutic agents. Glutamate plays an important role in the formation of traumatic memories, and in the pathophysiology and treatment of PTSD, highlighting several possible drug targets. Recent clinical studies demonstrate that infusion of ketamine, a glutamate NMDA receptor antagonist, rapidly and significantly reduces symptom severity in PTSD patients. In the present study, we examine the mechanisms underlying the actions of ketamine in a rodent model of fear conditioning, extinction, and renewal...
December 30, 2016: Neurobiology of Disease
https://www.readbyqxmd.com/read/28034445/higher-threat-avoidance-costs-reduce-avoidance-behaviour-which-in-turn-promotes-fear-extinction-in-humans
#11
Julina A Rattel, Stephan F Miedl, Jens Blechert, Frank H Wilhelm
Theoretical models specifying the underlying mechanisms of the development and maintenance of anxiety and related disorders state that fear responses acquired through classical Pavlovian conditioning are maintained by repeated avoidance behaviour; thus, it is assumed that avoidance prevents fear extinction. The present study investigated behavioural avoidance decisions as a function of avoidance costs in a naturalistic fear conditioning paradigm. Ecologically valid avoidance costs - manipulated between participant groups - were represented via time-delays during a detour in a gamified computer task...
December 15, 2016: Behaviour Research and Therapy
https://www.readbyqxmd.com/read/28025095/a-cross-species-study-of-heterogeneity-in-fear-extinction-learning-in-relation-to-fkbp5-variation-and-expression-implications-for-the-acute-treatment-of-posttraumatic-stress-disorder
#12
Isaac R Galatzer-Levy, Raül Andero, Takehito Sawamura, Tanja Jovanovic, Santiago Papini, Kerry J Ressler, Seth Davin Norrholm
Deficits in fear extinction learning are hypothesized to underlie the development of posttraumatic stress disorder (PTSD). Such deficits may, in part, be due to genetic and epigenetic variation in the stress related gene FKBP5. Conversely, altering FKBP5 epigenetic responses during memory consolidation may rescue extinction deficits making it a target for acute intervention to prevent the development of PTSD. Study 1 (Humans) examines if FKBP5 single nucleotide polymorphisms (SNPs) and PTSD symptom domains (re-experiencing, avoidance/numbing, hyperarousal) are associated with abnormal fear extinction phenotypes identified using latent growth mixture modeling (LGMM)...
December 23, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/28024275/stress-disrupts-the-reconsolidation-of-fear-memories-in-men
#13
Shira Meir Drexler, Oliver T Wolf
Reconsolidation is a post-retrieval process of restabilization of the memory trace. Previous findings from our group suggest that cortisol, a glucocorticoid hormone secreted in response to stress, enhances the reconsolidation of fear memories in healthy men. Cortisol effect was found to be very specific, enhancing only the fear memory that was reactivated (i.e. retrieved), but not the non-reactivated memory. In the current study we aimed to investigate the effects of psychosocial stress, a more ecologically valid intervention, on fear memory reconsolidation in men...
November 25, 2016: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/28018227/bidirectional-effects-of-cannabidiol-on-contextual-fear-memory-extinction
#14
Chenchen Song, Carl W Stevenson, Francisco S Guimaraes, Jonathan L C Lee
Cannabidiol (CBD) has been established to have both acute and long-lasting effects to reduce fear memory expression. The long-lasting impact might be mediated by an enhancement of memory extinction or an impairment of memory reconsolidation. Here, we directly compared the effects of i.p. injections of cannabidiol (10 mg/kg) with those of the NMDA receptor antagonist MK-801 (0.1 mg/kg) and partial agonist D-cycloserine (DCS; 15 mg/kg) in order to determine the mnemonic basis of long-term fear reduction. We showed that under conditions of strong fear conditioning, CBD reduced contextual fear memory expression both acutely during the extinction session as well as later at a fear retention test...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28009270/healing-pains-of-the-past-using-neuronal-transplantation
#15
XiaoTing Zheng, Sunil P Gandhi
Yang et al. (2016) show that transplantation of GABAergic inhibitory neurons into the amygdala boosts the persistence of fear extinction in mice. Transplantation was found to degrade perineuronal nets on endogenous inhibitory neurons and enhance synaptic plasticity in host amygdala.
December 21, 2016: Neuron
https://www.readbyqxmd.com/read/27994221/dynamic-modulation-of-inflammatory-pain-related-affective-and-sensory-symptoms-by-optical-control-of-amygdala-metabotropic-glutamate-receptor-4
#16
C Zussy, X Gómez-Santacana, X Rovira, D De Bundel, S Ferrazzo, D Bosch, D Asede, F Malhaire, F Acher, J Giraldo, E Valjent, I Ehrlich, F Ferraguti, J-P Pin, A Llebaria, C Goudet
Contrary to acute pain, chronic pain does not serve as a warning signal and must be considered as a disease per se. This pathology presents a sensory and psychological dimension at the origin of affective and cognitive disorders. Being largely refractory to current pharmacotherapies, identification of endogenous systems involved in persistent and chronic pain is crucial. The amygdala is a key brain region linking pain sensation with negative emotions. Here, we show that activation of a specific intrinsic neuromodulatory system within the amygdala associated with type 4 metabotropic glutamate receptors (mGlu4) abolishes sensory and affective symptoms of persistent pain such as hypersensitivity to pain, anxiety- and depression-related behaviors, and fear extinction impairment...
December 20, 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/27992092/posttraumatic-stress-disorder-perspectives-for-the-use-of-deep-brain-stimulation
#17
REVIEW
Roman Reznikov, Clement Hamani
OBJECTIVES: Deep Brain Stimulation (DBS) has been either approved or is currently under investigation for a number of psychiatric disorders. MATERIALS AND METHODS: We review clinical and preclinical concepts as well as the neurocircuitry that may be of relevance for the implementation of DBS in posttraumatic stress disorder (PTSD). RESULTS: PTSD is a chronic and debilitating illness associated with dysfunction in well-established neural circuits, including the amygdala and prefrontal cortex...
December 19, 2016: Neuromodulation: Journal of the International Neuromodulation Society
https://www.readbyqxmd.com/read/27981191/emergence-in-extinction-of-enhanced-and-persistent-responding-to-ambiguous-aversive-cues-is-associated-with-high-maoa-activity-in-the-prelimbic-cortex
#18
Guillaume L Poirier, Natsuko Hitora-Imamura, Carmen Sandi
There is a great deal of individual variability in the emotional outcomes of potentially traumatic events, and the underlying mechanisms are only beginning to be understood. In order to further our understanding of individual trajectories to trauma, its vulnerability and resilience, we adapted a model of fear expression to ambiguous vs perfect cues in adult male rats, and examined long-term fear extinction, 2, 3, and 50 days from acquisition. After the final conditioned fear test, mitochondrial enzyme monoamine oxidase A (MAOA) function was examined...
December 2016: Neurobiology of Stress
https://www.readbyqxmd.com/read/27977245/award-for-distinguished-scientific-early-career-contributions-to-psychology-nathan-m-holmes
#19
(no author information available yet)
The American Psychological Association's Awards for Distinguished Scientific Early Career Contributions to Psychology recognize psychologists who have demonstrated excellence early in their careers. One of the 2016 award winners is Nathan M. Holmes, whose work "has helped to elucidate the role of error-correction mechanisms in extinction, how extinguished and counter-conditioned fear responses are regulated by context and time, and how motivational states (such as fear) alter the content and neural substrates of associative formation...
November 2016: American Psychologist
https://www.readbyqxmd.com/read/27974618/neural-correlates-of-fear-in-the-periaqueductal-gray
#20
Thomas C Watson, Nadia L Cerminara, Bridget M Lumb, Richard Apps
: The dorsal and ventral periaqueductal gray (dPAG and vPAG, respectively) are embedded in distinct survival networks that coordinate, respectively, innate and conditioned fear-evoked freezing. However, the information encoded by the PAG during these survival behaviors is poorly understood. Recordings in the dPAG and vPAG in rats revealed differences in neuronal activity associated with the two behaviors. During innate fear, neuronal responses were significantly greater in the dPAG compared with the vPAG...
December 14, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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