Fear Conditioning Processes Research Articles

Decontextualized fear memories? Stronger conditioned fear responses during extinction learning and extinction recall in a safe context predict the development of long-term analog intrusions.

Difficulties in the context-dependent modulation of conditioned fear are known for posttraumatic stress disorder and may explain the occurrence of intrusive memories in safe contexts. The current study therefore investigated if reduced context-dependent modulation of conditioned fear and its underlying neural circuitry constitute risk factors for the development of analog intrusions in response to an experimental trauma. Eighty-five healthy women participated in the trauma film paradigm to investigate the development of analog intrusions as well as explicit memory for an experimental trauma after one week and three months, respectively. Before, participants underwent a context-dependent fear conditioning paradigm during functional magnetic resonance imaging with fear acquisition in context A and extinction training in context B on a first day, as well as extinction recall in context B and fear renewal in a novel context C one day later. Skin conductance responses (SCRs) and blood oxygen level dependent responses were main outcome measures. In addition to stronger fear acquisition in context A, stronger conditioned fear responses in the safe context B, as indicated by stronger conditioned SCRs or stronger activation of fear expressing regions during extinction learning and recall, predicted the development of long-term analog intrusions. Stronger fear responses in safe and danger contexts were risk factors for the development of long-term analog intrusions and point to decontextualized fear memories and difficulties in the context-dependent modulation of conditioned fear. Altered fear conditioning processes and reduced storage of contextual information may cause the occurrence of fear independent of context.

Effects of the retrieval-extinction paradigm with abstract reminders on fear memory extinction

Reactivated fear memories may enter an unstable state that could be interrupted by behavioral interventions such as the retrieval-extinction procedure. Studies of pharmacological interventions have shown that retrieval cues are not necessarily an exact reduplication of initial conditioned stimuli (CSs); they can instead be abstract word cues. However, the effectiveness of using abstract reminder cues in behavioral intervention procedures remains unknown, as do the conditions under which they are effective. The typicality of CS and the abstraction level of reminders are also likely to be important in the paradigm but have not been investigated to date. Here, in three experiments (n = 107), we manipulate the fear conditioning process, including single CS–unconditioned stimulus (US) and multiple CS–US connections, as well as the CS typicality and abstraction level of reminder cues, to explore the conditions for adopting retrieval-extinction with abstract reminders. The results of Experiments 1 and 2 show that the abstract cue is ineffective for use as a reminder in the procedure; this is the case for single exemplar category learning and perceptual discriminative learning, independent of the typicality of CS+ or the abstraction level of reminder cues. Only the outcome of Experiment 3, which contains multiple CS–US connections, shows no indication of fear return. The limitations of the study and possible interpretations of the results are discussed.

Fear Extinction Learning in Posttraumatic Stress Disorder.

Impairments in fear extinction processes have been implicated in the genesis and maintenance of debilitating psychopathologies, including Posttraumatic stress disorder(PTSD). PTSD, classified as a trauma- and stressor-related disorder, is characterized by four symptom clusters: intrusive recollections of trauma, avoidance of trauma-related stimuli, alterations in cognition and mood, and hyperarousal. One of the key pathological feature associated with the persistence of these symptoms is impaired fear extinction, as delineated in multiple studies employing Pavlovian fear-conditioning paradigms. These paradigms, comprising fear acquisition, extinction, extinction recall, and fear renewal phases, have illuminated the neurobiological substrates of PTSD. Dysfunctions in the neural circuits that mediate these fear learning and extinction processes can result in failure to extinguish fear responses and retain extinction memory, giving rise to enduring experience of fear and anxiety. The protective avoidance behaviors observed in individuals with PTSD further exacerbate intrusive symptoms and pose challenges to effective treatment strategies. A comprehensive analysis of fear conditioning and extinction processes, along with the underlying neurobiology, could significantly enhance our understanding of PTSD pathophysiology. This chapter delineates the role of fear extinction processes in PTSD, investigates the underlying neurobiological substrates, and underscores the therapeutic implications, while also identifying future research directions.

PTSD, Immune System, and Inflammation.

Posttraumatic stress disorder (PTSD) is a severe trauma and stress-related disorder associated with different somatic comorbidities, especially cardiovascular and metabolic disorders, and with chronic low-grade inflammation. Altered balance of the hypothalamic-pituitary-adrenal (HPA) axis, cytokines and chemokines, C-reactive protein, oxidative stress markers, kynurenine pathways, and gut microbiota might be involved in the alterations of certain brain regions regulating fear conditioning and memory processes, that are all altered in PTSD. In addition to the HPA axis, the gut microbiota maintains the balance and interaction of the immune, CNS, and endocrine pathways forming the gut-brain axis. Disbalance in the HPA axis, gut-brain axis, oxidative stress pathways and kynurenine pathways, altered immune signaling and disrupted homeostasis, as well as the association of the PTSD with the inflammation and disrupted cognition support the search for novel strategies for treatment of PTSD. Besides potential anti-inflammatory treatment, dietary interventions or the use of beneficial bacteria, such as probiotics, can potentially improve the composition and the function of the bacterial community in the gut. Therefore, bacterial supplements and controlled dietary changes, with exercise, might have beneficial effects on the psychological and cognitive functions in patients with PTSD. These new treatments should be aimed to attenuate inflammatory processes and consequently to reduce PTSD symptoms but also to improve cognition and reduce cardio-metabolic disorders associated so frequently with PTSD.

P105 Women with greater post-traumatic stress symptom severity and less disrupted sleep have improved fear extinction recall compared to men

Abstract Sleep has been found to play a key role in fear conditioning, extinction learning and extinction recall, the paradigm modelling the development, maintenance and treatment of anxiety disorders including post-traumatic stress disorder (PTSD), which are disorders commonly associated with sleep disturbances. Previous studies examining associations between sleep and fear or extinction processes predominately focused on objectively measured sleep architecture using polysomnography, and the majority of the research has been done in healthy populations. To date, little research has focused on subjective sleep measures and particularly in clinical populations including PTSD, which often experience subjectively poor sleep. Here we investigated whether subjective sleep disturbance, sleep onset latency, wake after sleep onset or sleep efficiency were related to fear conditioning, extinction learning or extinction recall in a large sample of individuals with a range of PTSD symptom severity and healthy controls. Overall, we did not find that sleep was associated with fear conditioning extinction learning or extinction recall. However, emerging evidence highlighting the critical role of sex in PTSD risk, fear conditioning processes, as well as in the sleep-fear conditioning relationship. Exploratory analyses examining sex-specific effects found that shorter sleep onset latency and greater sleep efficiency during the previous night were associated with improved extinction recall in women with higher PTSD symptom severity. This suggests that less time falling asleep and longer time asleep while in bed may be protective against the commonly observed impaired extinction recall in PTSD in highly symptomatic women, but is not relevant in men.

Sex differences in the effect of subjective sleep on fear conditioning, extinction learning, and extinction recall in individuals with a range of PTSD symptom severity

Sleep has been found to play a key role in fear conditioning, extinction learning and extinction recall, and sleep disturbances are linked to many mental disorders including post-traumatic stress disorder (PTSD). Previous studies examining associations between sleep and fear or extinction processes primarily focused on objectively measured sleep architecture. Little research has so far focused on subjective sleep measures and particularly in clinical populations, which often experience subjectively poor sleep, including PTSD. Here we investigated whether subjective sleep disturbance, sleep onset latency, wake after sleep onset or sleep efficiency were related to fear conditioning, extinction learning or extinction recall in a large sample of individuals with a range of PTSD symptom severity (n = 248). Overall, we did not find that subjective sleep was associated with fear conditioning or extinction processes. However, exploratory analyses examining the moderating effect of sex found that shorter sleep onset latency and greater sleep efficiency were associated with improved extinction recall in women with higher PTSD symptom severity. This suggests that less time falling asleep and longer time asleep while in bed may be protective in highly symptomatic women against the commonly observed impaired extinction recall in PTSD. More studies are needed to explore sex-specific effects further.

Impact of hormonal contraceptives on sex differences in fear conditioning and fear extinction in PTSD.

Sex differences in the neurobiological mechanisms involved in fear conditioning and extinction have been suggested to contribute to differential vulnerability for the development of posttraumatic stress disorder (PTSD) in women compared with men. Reproductive hormones, such as estradiol, have been shown to facilitate fear conditioning and extinction learning and may explain some of these differences. However, the effect of commonly used hormonal contraceptives on the neurobiological mechanisms of fear conditioning and extinction is poorly understood. A laboratory study was conducted in trauma-exposed men and women with and without full or partial PTSD to examine effects of sex and use of hormonal birth control on fear conditioning, fear extinction learning, and extinction retention. Participants underwent fear conditioning with stimuli that were paired (CS+) or unpaired (CS−) with shock. Extinction learning occurred 72 h later, and extinction retention was tested 1 wk after extinction. Women on hormonal contraceptives (HCs) demonstrated enhanced acquisition of fear conditioning and enhanced extinction of fear as compared with women off hormonal birth control and men. While clinical implications have yet to be determined, these results suggest that hormonal contraceptives may facilitate learning during both fear acquisition and extinction. Understanding the impact of sex and hormones on fear conditioning and extinction processes may lead to new insights into the pathophysiology of PTSD and result in advancements in treatment that may vary by sex.

Using Translational Models of Fear Conditioning to Uncover Sex-Linked Factors Related to PTSD Risk

Post-traumatic stress disorder (PTSD) is a debilitating neuropsychiatric disorder that follows exposure to a traumatic event; however, not every person who experiences trauma will develop PTSD. Women are more likely to be diagnosed with PTSD than men even when controlling for type and amount of trauma exposure. Circulating levels of gonadal hormones such as estradiol, progesterone, and testosterone may contribute to differential risk for developing PTSD. In this review, we briefly consider the influence of gonadal hormones on fear conditioning processes including fear acquisition, fear inhibition, extinction learning, and extinction recall within translational neuroscience models. We discuss findings from human studies incorporating samples from both community and traumatized clinical populations to further understand how these hormones might interact with exposure to trauma. Additionally, we propose that special attention should be paid to the specific measure used to examine fear conditioning processes as there is evidence that common psychophysiological indices such as skin conductance response and fear-potentiated startle can reveal quite different results and thus necessitate nuanced interpretations. Continued research to understand the influence of gonadal hormones in fear learning and extinction processes will provide further insight into the increased risk women have of developing PTSD and provide new targets for the treatment and prevention of this disorder.

The short-term dynamics of posttraumatic stress disorder symptoms during the acute posttrauma period.

The manner in which posttraumatic stress disorder (PTSD) develops remains largely unknown. PTSD is comprised of 20 symptoms across 4 clusters. These clusters were hypothesized to reflect a failure of recovery model in which intrusive symptoms appear first. Intrusive symptoms led to avoidance of trauma-related stimuli, which resulted in sustained arousal. The sustained arousal ultimately led to dysphoria. This hypothesized symptom progression was evaluated during the acute posttrauma period (the first 30 days postevent). Participants (N = 80) reported their PTSD symptoms for 30 days via mobile devices. Using a short-term dynamic modeling framework, a temporal and contemporaneous model of PTSD symptoms was obtained. In the temporal network, a fear-conditioning component was identified that supported the hypothesized set of relations among symptom clusters. The contemporaneous network was classified by two subnetworks. The first corresponded to a fear-conditioning model that included symptoms of intrusions and avoidance. The second included symptoms of dysphoria and arousal. These findings suggest that, after a trauma, there may be a fear-conditioning process that involves intrusions, avoidance, and arousal symptoms. Dysphoric symptoms were also present but developed as a partially distinct component.

The Influence of Combat Experience on Psychologically Healthy Soldiers' Attentiveness to Environmental Threats.

In contrast to previous research that has primarily examined how psychological disorders (e.g., post-traumatic stress disorder [PTSD], anxiety) are affected by and affect individuals' threat perceptions, this study examines the relationship between combat experience and threat-monitoring in psychologically healthy Soldiers. Existing research has established how prolonged or intense experiences with war-related stressors can lead individuals to undergo an unconscious fear-conditioning process that affects the circuitry of the prefrontal cortex, hippocampus, amygdala, and anterior cingulate cortex regions of the brain. We predict that the intensity of one's combat experience positively influences Soldiers' attention to environmental threats. Participants included U. S. Army Soldiers with a score of 50 or below on the PTSD Checklist-Military Version. Participants completed the Combat Exposure Scale and the State-Trait Anxiety Inventory. The experimental prediction task we employed assesses the expectation of an intrusively loud white noise sound that occurred on three variable patterns in a pseudorandomized order. Each tone pattern was used 20 times over a total of 60 trials. The experimental prediction task included two neutral tones (700 and 1,300 Hz) that were presented in a repeated pattern along with a 100-dB burst of white noise (0.5-second duration). In each trial, one of three possible tone combinations was presented. To assess their attentiveness to threats, participants were asked to continuously rate their expectancy of the burst of white noise using a visual analogue scale (VAS) ranging from 0 to 100. VAS ratings were collected at controlled points throughout the task. None of the participants reported scores on any of the diagnostic surveys that met standards for clinical significance. A repeated-measures analysis of variance was conducted to assess the overall effect of the three prediction conditions on participants' VAS ratings. There was a significant main effect for Combat Exposure Scale scores on VAS ratings [F(1, 27) = 5.19, p = 0.031], with high scorers demonstrating a generally higher expectancy of the white noise burst throughout the entire experimental sequence. Results suggest that within subclinical populations of Soldiers, the intensity of one's combat experience is positively associated with their attention to threats. These findings suggest that Soldiers who experience combat should be observed for signs of increased threat-attention bias, as this may indicate that their capacities for information processing, decision-making, and emotion regulation could be compromised. The positive relationship we observe between a level of combat experience and attentional biases toward threatening stimuli may also help to explain why these veterans engage in "externalizing" behaviors that are risky, aggressive, or violent as well as relational problems and antisocial behaviors that are reported in higher-than-average rates among these populations of Soldiers. Acknowledging that increased threat attention may be a preclinical indication of developing PTSD or other related psychological conditions (e.g., depression, anxiety) should motivate clinicians to more actively diagnose and treat this condition.

Sex differences in stress effects on emotional learning.

Stress influences emotional learning and memory processes. These effects are thought to underlie stress-associated mental disorders. Sex differences in stress reactivity and in central nervous system stress sensitivity illustrate the important modulatory role of sex hormones. This Review outlines how stress hormones influence different stages of the fear conditioning process, such as fear acquisition, extinction, and retrieval. Results will be compared with findings on the impact of stress on episodic memory. The focus is on the available human data on sex differences and the impact sex hormones have on the stress effects on emotional learning and memory. It will become apparent that the menstrual cycle but also the intake of hormonal contraceptives modulates the impact of stress on brain and behavior. Additional basic research is needed for a deeper insight regarding the interplay between stress and sex hormones in emotion and cognition. In addition, new treatment options might be derived to optimize existing strategies such as exposure therapy, which relies on the principles of fear conditioning. © 2016 Wiley Periodicals, Inc.

Sex differences in conditioned stimulus discrimination during context-dependent fear learning and its retrieval in humans: the role of biological sex, contraceptives and menstrual cycle phases

Anxiety disorders are more prevalent in women than in men. Despite this sexual dimorphism, most experimental studies are conducted in male participants and studies focusing on sex differences are sparse. In addition, the role of hormonal contraceptives and menstrual cycle phase in fear conditioning and extinction processes remain largely unknown. We investigated sex differences in context-dependent fear acquisition and extinction (day 1) and their retrieval/expression (day 2). Skin conductance responses (SCRs), fear and unconditioned stimulus expectancy ratings were obtained. We included 377 individuals (261 women) in our study. Robust sex differences were observed in all dependent measures. Women generally displayed higher subjective ratings but smaller SCRs than men and showed reduced excitatory/inhibitory conditioned stimulus (CS+/CS-) discrimination in all dependent measures. Furthermore, women using hormonal contraceptives showed reduced SCR CS discrimination on day 2 than men and free-cycling women, while menstrual cycle phase had no effect. Possible limitations include the simultaneous testing of up to 4 participants in cubicles, which might have introduced a social component, and not assessing postexperimental contingency awareness. The response pattern in women shows striking similarity to previously reported sex differences in patients with anxiety. Our results suggest that pronounced deficits in associative discrimination learning and subjective expression of safety information (CS- responses) might underlie higher prevalence and higher symptom rates seen in women with anxiety disorders. The data call for consideration of biological sex and hormonal contraceptive use in future studies and may suggest that targeting inhibitory learning during therapy might aid precision medicine.

Non-Antidepressant Long-term Treatment in Post-Traumatic Stress Disorder (PTSD)

Post-traumatic stress disorder (PTSD) is a frequent and disabling condition that occurs after exposure to a traumatic event, and Selective Serotonin Reuptake Inhibitors (SSRIs) are considered the first-line treatment approach for this disorder. However, a large proportion of patients remain symptomatic and other pharmacological agents have been investigated, based on the understanding of the underlying biological dysfunctions of PTSD. We conducted a review of the literature on the pharmacological options for PTSD other than the antidepressants, using MedLine and Web of Science databases, with search terms including the pharmacologic class of each agent plus PTSD, or pharmacotherapy, or fear conditioning. The literature review covered articles published until august 2012, including reviews and original articles. Agents like antipsychotics, anticonvulsants, benzodiazepines, anti-adrenergic agents, have been studied in randomized clinical trials (RCTs), with general positive results for antipsychotics, especially as adjunct therapy, and for prazosin for sleep-related disturbances. However, one important target for novel medications is the modulation of the fear conditioning process, through the alteration of retrieval/reconsolidation or enhancement of fear extinction. This is traditionally targeted in prolonged exposure therapy, but pre-clinical findings from studies investigating agents like propanolol, clonidine, N-Methyl-D-aspartic Acid Receptor (NMDAR) compounds, 3,4-methylenedioxy-N-methylamphetamine (MDMA) and cannabinoids, indicate promising results in affecting the fear conditioning process and thus improving PTSD core symptoms. Antipsychotics can be considered a reasonable alternative option to PTSD, with the largest body of evidence for risperidone, even though larger RCTs are warranted. Prazosin is also a promising agent, especially for sleep-related disturbances, while anticonvulsants and benzodiazepines lack empirical support. However, the most promising area for pharmacotherapy in PTSD is the modulation of the fear conditioning process, through agents used in adjunct to exposure therapy.

Neural signatures of human fear conditioning: an updated and extended meta-analysis of fMRI studies.

Classical Pavlovian fear conditioning remains the most widely employed experimental model of fear and anxiety, and continues to inform contemporary pathophysiological accounts of clinical anxiety disorders. Despite its widespread application in human and animal studies, the neurobiological basis of fear conditioning remains only partially understood. Here we provide a comprehensive meta-analysis of human fear-conditioning studies carried out with functional magnetic resonance imaging (fMRI), yielding a pooled sample of 677 participants from 27 independent studies. As a distinguishing feature of this meta-analysis, original statistical brain maps were obtained from the authors of 13 of these studies. Our primary analyses demonstrate that human fear conditioning is associated with a consistent and robust pattern of neural activation across a hypothesized genuine network of brain regions resembling existing anatomical descriptions of the 'central autonomic-interoceptive network'. This finding is discussed with a particular emphasis on the neural substrates of conscious fear processing. Our associated meta-analysis of functional deactivations-a scarcely addressed dynamic in fMRI fear-conditioning studies-also suggests the existence of a coordinated brain response potentially underlying the 'safety signal' (that is, non-threat) processing. We attempt to provide an integrated summary on these findings with the view that they may inform ongoing studies of fear-conditioning processes both in healthy and clinical populations, as investigated with neuroimaging and other experimental approaches.

Stress differentially affects fear conditioning in men and women

Stress and fear conditioning processes are both important vulnerability factors in the development of psychiatric disorders. In behavioral studies considerable sex differences in fear learning have been observed after increases of the stress hormone cortisol. But neuroimaging experiments, which give insights into the neurobiological correlates of stress × sex interactions in fear conditioning, are lacking so far. In the current functional magnetic resonance imaging (fMRI) study, we tested whether a psychosocial stressor (Trier Social Stress Test) compared to a control condition influenced subsequent fear conditioning in 48 men and 48 women taking oral contraceptives (OCs). One of two pictures of a geometrical figure was always paired (conditioned stimulus, CS+) or never paired (CS-) with an electrical stimulation (unconditioned stimulus). BOLD responses as well as skin conductance responses were assessed. Sex-independently, stress enhanced the CS+/CS- differentiation in the hippocampus in early acquisition but attenuated conditioned responses in the medial frontal cortex in late acquisition. In early acquisition, stress reduced the CS+/CS- differentiation in the nucleus accumbens in men, but enhanced it in OC women. In late acquisition, the same pattern (reduction in men, enhancement in OC women) was found in the amygdala as well as in the anterior cingulate. Thus, psychosocial stress impaired the neuronal correlates of fear learning and expression in men, but facilitated them in OC women. A sex-specific modulation of fear conditioning after stress might contribute to the divergent prevalence of men and women in developing psychiatric disorders.

No effect of trait anxiety on differential fear conditioning or fear generalization

Previous studies have shown that individuals with anxiety disorders exhibit deficits in fear inhibition and excessive generalization of fear, but little data exist on individuals at risk from these disorders. The present study examined the role of trait anxiety in the acquisition and generalization of fear in 126 healthy participants selected on the basis of their trait-anxiety scores. Measures of conditioning included fear-potentiated startle, skin conductance response and online risk ratings for the unconditioned stimulus. Contrary to our hypotheses, trait anxiety did not have any effect either on the acquisition or the generalization of fear. Our results suggest that these fear conditioning processes are not impaired in individuals at risk from anxiety.

Outlining new frontiers for the comprehension of obsessive-compulsive disorder: a review of its relationship with fear and anxiety

Anxiety is an important component of the psychopathology of the obsessive-compulsive disorder (OCD). So far, most interventions that have proven to be effective for treating OCD are similar to those developed for other anxiety disorders. However, neurobiological studies of OCD came to conclusions that are not always compatible with those previously associated with other anxiety disorders. The aim of this study is to review the degree of overlap between OCD and other anxiety disorders phenomenology and pathophysiology to support the rationale that guides research in this field. Clues about the neurocircuits involved in the manifestation of anxiety disorders have been obtained through the study of animal anxiety models, and structural and functional neuroimaging in humans. These investigations suggest that in OCD, in addition to dysfunction in cortico-striatal pathways, the functioning of an alternative neurocircuitry, which involves amygdalo-cortical interactions and participates in fear conditioning and extinction processes, may be impaired. It is likely that anxiety is a relevant dimension of OCD that impacts on other features of this disorder. Therefore, future studies may benefit from the investigation of the expression of fear and anxiety by OCD patients according to their type of obsessions and compulsions, age of OCD onset, comorbidities, and patterns of treatment response.

The role of NCAM in auditory fear conditioning and its modulation by stress: a focus on the amygdala

Chronic stress in rodents was shown to induce structural shrinkage and functional alterations in the hippocampus that were linked to spatial memory impairments. Effects of chronic stress on the amygdala have been linked to a facilitation of fear conditioning. Although the underlying molecular mechanisms are still poorly understood, increasing evidence highlights the neural cell adhesion molecule (NCAM) as an important molecular mediator of stress-induced structural and functional alterations. In this study, we investigated whether altered NCAM expression levels in the amygdala might be related to stress-induced enhancement of auditory fear conditioning and anxiety-like behavior. In adult C57BL/6J wild-type mice, chronic unpredictable stress resulted in an isoform-specific increase of NCAM expression (NCAM-140 and NCAM-180) in the amygdala, as well as enhanced auditory fear conditioning and anxiety-like behavior. Strikingly, forebrain-specific conditional NCAM-deficient mice (NCAM-floxed mice that express the cre-recombinase under the control of the promoter of the alpha-subunit of the calcium-calmodulin-dependent protein kinase II), whose amygdala NCAM expression levels are reduced, displayed impaired auditory fear conditioning which was not altered following chronic stress exposure. Likewise, chronic stress in these conditional NCAM-deficient mice did not modify NCAM expression levels in the amygdala or hippocampus, while they showed enhanced anxiety-like behavior, questioning the involvement of NCAM in this type of behavior. Together, our results strongly support the involvement of NCAM in the amygdala in the consolidation of auditory fear conditioning and highlight increased NCAM expression in the amygdala among the mechanisms whereby stress facilitates fear conditioning processes.

The Influence of Stress Hormones on Fear Circuitry

Fear arousal, initiated by an environmental threat, leads to activation of the stress response, a state of alarm that promotes an array of autonomic and endocrine changes designed to aid self-preservation. The stress response includes the release of glucocorticoids from the adrenal cortex and catecholamines from the adrenal medulla and sympathetic nerves. These stress hormones, in turn, provide feedback to the brain and influence neural structures that control emotion and cognition. To illustrate this influence, we focus on how it impacts fear conditioning, a behavioral paradigm widely used to study the neural mechanisms underlying the acquisition, expression, consolidation, reconsolidation, and extinction of emotional memories. We also discuss how stress and the endocrine mediators of the stress response influence the morphological and electrophysiological properties of neurons in brain areas that are crucial for fear-conditioning processes, including the amygdala, hippocampus, and prefrontal cortex. The information in this review illuminates the behavioral and cellular events that underlie the feedforward and feedback networks that mediate states of fear and stress and their interaction in the brain.

Efficacy and mechanism of action of intrahippocampal D-cycloserine in an animal model of post-traumatic stress disorder

Event Abstract Back to Event Efficacy and mechanism of action of intrahippocampal D-cycloserine in an animal model of post-traumatic stress disorder Lorren Fairbairn1*, Soraya Seedat1 and Willie Daniels2 1 University of Sellenbosch, Department of Psychiatry, South Africa 2 University of Kwazulu-Natal, South Africa Background: One of the most prevalent anxiety disorders is posttraumatic stress disorder (PTSD), of which current therapies are based on the processes of fear extinction. Specifically cognitive behaviour therapy (exposure-based) in humans is procedurally very analogous to extinction training in animal models of emotional learning [1].Recent studies have alluded to the mechanisms underlying fear extinction which in turn has given rise to the hypothesis that dysfunctional fear extinction plays a vital role in the development of PTSD pathophysiology. DCS and its facilitative effects are currently under investigation in clinical studies of PTSD in order to enhance fear extinction techniques. However, attempts to identify specific mechanisms by which DCS enhances loss of fear in humans have provided few insights. Considering the known impact of trauma and stress on early brain development, further studies need to be conducted in order to elucidate the mechanisms underlying PTSD symptomatology in adolescents. Aim: Therefore the proposed animal study aims to extend the current state of knowledge of the effects of DCS on anxiety reduction in adolescent and adult rats, hypothesizing that these are associated with adaptive learning. Methodology: Since associative fear conditioning and non-associative sensitization processes have been suggested as contributors towards exaggerated implicit fear memory [2], a PTSD model tapping into both of these fear components following the experience of a trauma, will be used. A brief but intense electric footshock will be applied [3]. Behaviour, neurotrophin levels, gene expression and protein synthesis will be measured.Results:Pending.Should be available in time for congress. Significance: The proposed study is of significant value in addressing the molecular mechanisms of PTSD in the context of the current limited availability of effective therapeutic strategies for fear extinction.