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Sample records for classical fear conditioning

  1. Unconditioned responses and functional fear networks in human classical conditioning

    OpenAIRE

    Linnman, Clas; Rougemont-Bücking, Ansgar; Beucke, Jan Carl; Zeffiro, Thomas A.; Milad, Mohammed R.

    2011-01-01

    Human imaging studies examining fear conditioning have mainly focused on the neural responses to conditioned cues. In contrast, the neural basis of the unconditioned response and the mechanisms by which fear modulates inter-regional functional coupling have received limited attention. We examined the neural responses to an unconditioned stimulus using a partial-reinforcement fear conditioning paradigm and functional MRI. The analysis focused on: (1) the effects of an unconditioned stimulus (a...

  2. Unconditioned responses and functional fear networks in human classical conditioning.

    Science.gov (United States)

    Linnman, Clas; Rougemont-Bücking, Ansgar; Beucke, Jan Carl; Zeffiro, Thomas A; Milad, Mohammed R

    2011-08-01

    Human imaging studies examining fear conditioning have mainly focused on the neural responses to conditioned cues. In contrast, the neural basis of the unconditioned response and the mechanisms by which fear modulates inter-regional functional coupling have received limited attention. We examined the neural responses to an unconditioned stimulus using a partial-reinforcement fear conditioning paradigm and functional MRI. The analysis focused on: (1) the effects of an unconditioned stimulus (an electric shock) that was either expected and actually delivered, or expected but not delivered, and (2) on how related brain activity changed across conditioning trials, and (3) how shock expectation influenced inter-regional coupling within the fear network. We found that: (1) the delivery of the shock engaged the red nucleus, amygdale, dorsal striatum, insula, somatosensory and cingulate cortices, (2) when the shock was expected but not delivered, only the red nucleus, the anterior insular and dorsal anterior cingulate cortices showed activity increases that were sustained across trials, and (3) psycho-physiological interaction analysis demonstrated that fear led to increased red nucleus coupling to insula but decreased hippocampus coupling to the red nucleus, thalamus and cerebellum. The hippocampus and the anterior insula may serve as hubs facilitating the switch between engagement of a defensive immediate fear network and a resting network. PMID:21377494

  3. Conditioned fear in adult rats is facilitated by the prior acquisition of a classically conditioned motor response

    OpenAIRE

    Lindquist, Derick H.; Mahoney, Luke P.; Steinmetz, Joseph E.

    2010-01-01

    Early in eyeblink classical conditioning, amygdala-dependent fear responding is reported to facilitate acquisition of the cerebellar-dependent eyeblink conditioned response (CR), in accord with the two-process model of conditioning (Konorski, 1967). In the current study, we predicted that the conditioned fear (e.g., freezing) observed during eyeblink conditioning may become autonomous of the eyeblink CR and amenable to further associative modification. Conditioned freezing was assessed during...

  4. Limbic system development underlies the emergence of classical fear conditioning during the third and fourth weeks of life in the rat.

    Science.gov (United States)

    Deal, Alex L; Erickson, Kristen J; Shiers, Stephanie I; Burman, Michael A

    2016-04-01

    Classical fear conditioning creates an association between an aversive stimulus and a neutral stimulus. Although the requisite neural circuitry is well understood in mature organisms, the development of these circuits is less well studied. The current experiments examine the ontogeny of fear conditioning and relate it to neuronal activation assessed through immediate early gene (IEG) expression in the amygdala, hippocampus, perirhinal cortex, and hypothalamus of periweanling rats. Rat pups were fear conditioned, or not, during the third or fourth weeks of life. Neuronal activation was assessed by quantifying expression of FBJ osteosarcoma oncogene (FOS) using immunohistochemistry (IHC) in Experiment 1. Fos and early growth response gene-1 (EGR1) expression was assessed using qRT-PCR in Experiment 2. Behavioral data confirm that both auditory and contextual fear continue to emerge between PD 17 and 24. The IEG expression data are highly consistent with these behavioral results. IHC results demonstrate significantly more FOS protein expression in the basal amygdala of fear-conditioned PD 23 subjects compared to control subjects, but no significant difference at PD 17. qRT-PCR results suggest specific activation of the amygdala only in older subjects during auditory fear expression. A similar effect of age and conditioning status was also observed in the perirhinal cortex during both contextual and auditory fear expression. Overall, the development of fear conditioning occurring between the third and fourth weeks of life appears to be at least partly attributable to changes in activation of the amygdala and perirhinal cortex during fear conditioning or expression. (PsycINFO Database Record PMID:26820587

  5. Extinction in human fear conditioning

    OpenAIRE

    Hermans, Dirk; Craske, Michelle G.; Mineka, Susan; Lovibond, Peter F.

    2006-01-01

    Although most extinction research is conducted in animal laboratories, the study of extinction learning in human fear conditioning has gained increasing attention over the last decade. The most important findings from human fear extinction are reviewed in this article. Specifically, we review experimental investigations of the impact of conditioned inhibitors, conditioned exciters, context renewal, and reinstatement on fear extinction in human samples. We discuss data from laboratory studies ...

  6. Fear Conditioning Increases NREM Sleep

    OpenAIRE

    HELLMAN, Kevin; Abel, Ted

    2007-01-01

    To understand the role that sleep may play in memory storage, the authors investigated how fear conditioning affects sleep–wake states by performing electroencephalographic (EEG) and electromyographic recordings of C57BL/6J mice receiving fear conditioning, exposure to conditioning stimuli, or immediate shock treatment. This experimental design allowed us to examine the effects of associative learning, presentation of the conditioning stimuli, and presentation of the unconditioned stimuli on ...

  7. Trace Fear Conditioning in Mice

    OpenAIRE

    Lugo, Joaquin N.; Smith, Gregory D; Holley, Andrew J.

    2014-01-01

    In this experiment we present a technique to measure learning and memory. In the trace fear conditioning protocol presented here there are five pairings between a neutral stimulus and an unconditioned stimulus. There is a 20 sec trace period that separates each conditioning trial. On the following day freezing is measured during presentation of the conditioned stimulus (CS) and trace period. On the third day there is an 8 min test to measure contextual memory. The representative results are f...

  8. Working memory and fear conditioning

    OpenAIRE

    Carter, Ronald McKell; Hofstötter, Constanze; Tsuchiya, Naotsugu; Koch, Christof

    2003-01-01

    Previous studies of associative learning implicate higher-level cognitive processes in some forms of classical conditioning. An ongoing debate is concerned with the extent to which attention and awareness are necessary for trace but not delay eye-blink conditioning [Clark, R. E. & Squire, L. R. (1998) Science 280, 77-81; Lovibond, P. F. & Shanks, D. (2002) J. Exp. Psychol. Anim. Behav. Processes 28, 38-42]. In trace conditioning, a short interval is interposed between the termination of the c...

  9. Extending animal models of fear conditioning to humans.

    Science.gov (United States)

    Delgado, M R; Olsson, A; Phelps, E A

    2006-07-01

    A goal of fear and anxiety research is to understand how to treat the potentially devastating effects of anxiety disorders in humans. Much of this research utilizes classical fear conditioning, a simple paradigm that has been extensively investigated in animals, helping outline a brain circuitry thought to be responsible for the acquisition, expression and extinction of fear. The findings from non-human animal research have more recently been substantiated and extended in humans, using neuropsychological and neuroimaging methodologies. Research across species concur that the neural correlates of fear conditioning include involvement of the amygdala during all stages of fear learning, and prefrontal areas during the extinction phase. This manuscript reviews how animal models of fear are translated to human behavior, and how some fears are more easily acquired in humans (i.e., social-cultural). Finally, using the knowledge provided by a rich animal literature, we attempt to extend these findings to human models targeted to helping facilitate extinction or abolishment of fears, a trademark of anxiety disorders, by discussing efficacy in modulating the brain circuitry involved in fear conditioning via pharmacological treatments or emotion regulation cognitive strategies. PMID:16472906

  10. Modeling fear-conditioned bradycardia in humans

    OpenAIRE

    Castegnetti, G.; Tzovara, A.; Staib, M.; Paulus, P. C.; Hofer, N.; Bach, D R

    2016-01-01

    Across species, cued fear conditioning is a common experimental paradigm to investigate aversive Pavlovian learning. While fear-conditioned stimuli (CS+) elicit overt behavior in many mammals, this is not the case in humans. Typically, autonomic nervous system activity is used to quantify fear memory in humans, measured by skin conductance responses (SCR). Here, we investigate whether heart period responses (HPR) evoked by the CS, often observed in humans and small mammals, are suitable to co...

  11. Adrenergic Transmission Facilitates Extinction of Conditional Fear in Mice

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    Barad, Mark; Cain, Christopher K.; Blouin, Ashley M.

    2004-01-01

    Extinction of classically conditioned fear, like its acquisition, is active learning, but little is known about its molecular mechanisms. We recently reported that temporal massing of conditional stimulus (CS) presentations improves extinction memory acquisition, and suggested that temporal spacing was less effective because individual CS…

  12. Modeling fear-conditioned bradycardia in humans.

    Science.gov (United States)

    Castegnetti, Giuseppe; Tzovara, Athina; Staib, Matthias; Paulus, Philipp C; Hofer, Nicolas; Bach, Dominik R

    2016-06-01

    Across species, cued fear conditioning is a common experimental paradigm to investigate aversive Pavlovian learning. While fear-conditioned stimuli (CS+) elicit overt behavior in many mammals, this is not the case in humans. Typically, autonomic nervous system activity is used to quantify fear memory in humans, measured by skin conductance responses (SCR). Here, we investigate whether heart period responses (HPR) evoked by the CS, often observed in humans and small mammals, are suitable to complement SCR as an index of fear memory in humans. We analyze four datasets involving delay and trace conditioning, in which heart beats are identified via electrocardiogram or pulse oximetry, to show that fear-conditioned heart rate deceleration (bradycardia) is elicited and robustly distinguishes CS+ from CS-. We then develop a psychophysiological model (PsPM) of fear-conditioned HPR. This PsPM is inverted to yield estimates of autonomic input into the heart. We show that the sensitivity to distinguish CS+ and CS- (predictive validity) is higher for model-based estimates than peak-scoring analysis, and compare this with SCR. Our work provides a novel tool to investigate fear memory in humans that allows direct comparison between species. PMID:26950648

  13. Worrying Affects Associative Fear Learning: A Startle Fear Conditioning Study

    OpenAIRE

    Gazendam, F.J.; Kindt, M

    2012-01-01

    A valuable experimental model for the pathogenesis of anxiety disorders is that they originate from a learned association between an intrinsically non-aversive event (Conditioned Stimulus, CS) and an anticipated disaster (Unconditioned Stimulus, UCS). Most anxiety disorders, however, do not evolve from a traumatic experience. Insights from neuroscience show that memory can be modified post-learning, which may elucidate how pathological fear can develop after relatively mild aversive events. W...

  14. Demographic factors predict magnitude of conditioned fear.

    Science.gov (United States)

    Rosenbaum, Blake L; Bui, Eric; Marin, Marie-France; Holt, Daphne J; Lasko, Natasha B; Pitman, Roger K; Orr, Scott P; Milad, Mohammed R

    2015-10-01

    There is substantial variability across individuals in the magnitudes of their skin conductance (SC) responses during the acquisition and extinction of conditioned fear. To manage this variability, subjects may be matched for demographic variables, such as age, gender and education. However, limited data exist addressing how much variability in conditioned SC responses is actually explained by these variables. The present study assessed the influence of age, gender and education on the SC responses of 222 subjects who underwent the same differential conditioning paradigm. The demographic variables were found to predict a small but significant amount of variability in conditioned responding during fear acquisition, but not fear extinction learning or extinction recall. A larger differential change in SC during acquisition was associated with more education. Older participants and women showed smaller differential SC during acquisition. Our findings support the need to consider age, gender and education when studying fear acquisition but not necessarily when examining fear extinction learning and recall. Variability in demographic factors across studies may partially explain the difficulty in reproducing some SC findings. PMID:26151498

  15. Sex differences in learning processes of classical and operant conditioning

    OpenAIRE

    Dalla, Christina; Shors, Tracey J.

    2009-01-01

    Males and females learn and remember differently at different times in their lives. These differences occur in most species, from invertebrates to humans. We review here sex differences as they occur in laboratory rodent species. We focus on classical and operant conditioning paradigms, including classical eyeblink conditioning, fear conditioning, active avoidance and conditioned taste aversion. Sex differences have been reported during acquisition, retention and extinction in most of these p...

  16. Fear conditioning in frontotemporal lobar degeneration and Alzheimer's disease

    OpenAIRE

    Hoefer, M.; Allison, S. C.; Schauer, G. F.; Neuhaus, J M; Hall, J.; Dang, J. N.; Weiner, M.W.; Miller, B. L.; Rosen, H.J.

    2008-01-01

    Emotional blunting and abnormal processing of rewards and punishments represent early features of frontotemporal lobar degeneration (FTLD). Better understanding of the physiological underpinnings of these emotional changes can be facilitated by the use of classical psychology approaches. Fear conditioning (FC) is an extensively used paradigm for studying emotional processing that has rarely been applied to the study of dementia.We studied FC in controls (n = 25), Alzheimer's disease (n =25) a...

  17. Fear conditioning- and extinction-induced neuronal plasticity in the mouse amygdala

    OpenAIRE

    Ciocchi, Stéphane

    2009-01-01

    Experience-dependent changes in behavior are mediated by long-term functional modifications in brain circuits. To study the underlying mechanisms, our lab is using classical auditory fear conditioning, a simple and robust form of associative learning. In classical fear conditioning, the subject is exposed to a noxious unconditioned stimulus (US), such as a foot-shock, in conjunction with a neutral conditioned stimulus (CS), such as a tone or a light. As a result of the training, the tone acqu...

  18. [Mechanisms for regulation of fear conditioning and memory].

    Science.gov (United States)

    Kida, Satoshi

    2014-11-01

    Pavlovian fear conditioning is a model of fear learning and memory. The mechanisms regulating fear conditioning and memory have been investigated in humans and rodents. In this paradigm, animals learn and memorize an association between a conditioned stimulus (CS), such as context, and an unconditioned stimulus (US), such as an electrical footshock that induces fear. Fear memory generated though fear conditioning is stabilized via a memory consolidation process. Moreover, recent studies have shown the existence of memory processes that control fear memory following the retrieval of consolidated memory. Indeed, when fear memory is retrieved by re-exposure to the CS, the retrieved memory is re-stabilized via the reconsolidation process. On the other hand, the retrieval of fear memory by prolonged re-exposure to the CS also leads to fear memory extinction, new inhibitory learning against the fear memory, in which animals learn that they do not need to respond to the CS. Importantly, the reinforcement of fear memory after retrieval (i.e., re-experience such as flashbacks or nightmares) has been thought to be associated with the development of emotional disorders such as post-traumatic stress disorder (PTSD). In this review, I summarize recent progress in studies on the mechanism of fear conditioning and memory consolidation, reconsolidation and extinction, and furthermore, introduce our recent establishment of a mouse PTSD model that shows enhancement of fear memory after retrieval. PMID:25536762

  19. Hippocampal Structural Plasticity Accompanies the Resulting Contextual Fear Memory Following Stress and Fear Conditioning

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    Giachero, Marcelo; Calfa, Gaston D.; Molina, Victor A.

    2013-01-01

    The present research investigated the resulting contextual fear memory and structural plasticity changes in the dorsal hippocampus (DH) following stress and fear conditioning. This combination enhanced fear retention and increased the number of total and mature dendritic spines in DH. Intra-basolateral amygdala (BLA) infusion of midazolam prior to…

  20. Generalization of Conditioned Fear along a Dimension of Increasing Fear Intensity

    Science.gov (United States)

    Dunsmoor, Joseph E.; Mitroff, Stephen R.; LaBar, Kevin S.

    2009-01-01

    The present study investigated the extent to which fear generalization in humans is determined by the amount of fear intensity in nonconditioned stimuli relative to a perceptually similar conditioned stimulus. Stimuli consisted of graded emotionally expressive faces of the same identity morphed between neutral and fearful endpoints. Two…

  1. A model of amygdala-hippocampal-prefrontal interaction in fear conditioning and extinction in animals

    OpenAIRE

    Moustafa, Ahmed A.; Gilbertson, Mark W.; Orr, Scott P.; Herzallah, Mohammad M.; Servatius, Richard J.; Myers, Catherine E.

    2012-01-01

    Empirical research has shown that the amygdala, hippocampus, and ventromedial prefrontal cortex (vmPFC) are involved in fear conditioning. However, the functional contribution of each brain area and the nature of their interactions are not clearly understood. Here, we extend existing neural network models of the functional roles of the hippocampus in classical conditioning to include interactions with the amygdala and prefrontal cortex. We apply the model to fear conditioning, in which animal...

  2. Equal pain—Unequal fear response: enhanced susceptibility of tooth pain to fear conditioning

    Science.gov (United States)

    Meier, Michael L.; de Matos, Nuno M. P.; Brügger, Mike; Ettlin, Dominik A.; Lukic, Nenad; Cheetham, Marcus; Jäncke, Lutz; Lutz, Kai

    2014-01-01

    Experimental fear conditioning in humans is widely used as a model to investigate the neural basis of fear learning and to unravel the pathogenesis of anxiety disorders. It has been observed that fear conditioning depends on stimulus salience and subject vulnerability to fear. It is further known that the prevalence of dental-related fear and phobia is exceedingly high in the population. Dental phobia is unique as no other body part is associated with a specific phobia. Therefore, we hypothesized that painful dental stimuli exhibit an enhanced susceptibility to fear conditioning when comparing to equal perceived stimuli applied to other body sites. Differential susceptibility to pain-related fear was investigated by analyzing responses to an unconditioned stimulus (UCS) applied to the right maxillary canine (UCS-c) vs. the right tibia (UCS-t). For fear conditioning, UCS-c and USC-t consisted of painful electric stimuli, carefully matched at both application sites for equal intensity and quality perception. UCSs were paired to simple geometrical forms which served as conditioned stimuli (CS+). Unpaired CS+ were presented for eliciting and analyzing conditioned fear responses. Outcome parameter were (1) skin conductance changes and (2) time-dependent brain activity (BOLD responses) in fear-related brain regions such as the amygdala, anterior cingulate cortex, insula, thalamus, orbitofrontal cortex, and medial prefrontal cortex. A preferential susceptibility of dental pain to fear conditioning was observed, reflected by heightened skin conductance responses and enhanced time-dependent brain activity (BOLD responses) in the fear network. For the first time, this study demonstrates fear-related neurobiological mechanisms that point toward a superior conditionability of tooth pain. Beside traumatic dental experiences our results offer novel evidence that might explain the high prevalence of dental-related fears in the population. PMID:25100974

  3. Equal pain – Unequal fear response: Enhanced susceptibility of tooth pain to fear conditioning

    Directory of Open Access Journals (Sweden)

    Michael Lukas Meier

    2014-07-01

    Full Text Available Experimental fear conditioning in humans is widely used as a model to investigate the neural basis of fear learning and to unravel the pathogenesis of anxiety disorders. It has been observed that fear conditioning depends on stimulus salience and subject vulnerability to fear. It is further known that the prevalence of dental-related fear and phobia is exceedingly high in the population. Dental phobia is unique as no other body part is associated with a specific phobia. Therefore, we hypothesized that painful dental stimuli exhibit an enhanced susceptibility to fear conditioning when comparing to equal perceived stimuli applied to other body sites. Differential susceptibility to pain-related fear was investigated by analyzing responses to an unconditioned stimulus (UCS applied to the right maxillary canine (UCS-c versus the right tibia (UCS-t. For fear conditioning, UCS-c and USC-t consisted of painful electric stimuli, carefully matched at both application sites for equal intensity and quality perception. UCSs were paired to simple geometrical forms which served as conditioned stimuli (CS+. Unpaired CS+ were presented for eliciting and analyzing conditioned fear responses. Outcome parameter were 1 skin conductance changes and 2 time-dependent brain activity (BOLD responses in fear-related brain regions such as the amygdala, anterior cingulate cortex, insula, thalamus, orbitofrontal cortex and medial prefrontal cortex.A preferential susceptibility of dental pain to fear conditioning was observed, reflected by heightened skin conductance responses and enhanced time-dependent brain activity (BOLD responses in the fear network. For the first time, this study demonstrates fear-related neurobiological mechanisms that point towards a superior conditionability of tooth pain. Beside traumatic dental experiences our results offer novel evidence that might explain the high prevalence of dental-related fears in the population.

  4. Fear conditioning by proxy: social transmission of fear during memory retrieval

    OpenAIRE

    Bruchey, Aleksandra K.; Jones, Carolyn E.; Monfils, Marie-H.

    2010-01-01

    After fear conditioning (e.g., by pairing a tone to a shock), memory retrieval typically leads to fear expression (e.g., freezing to the tone). Here, we examined the effect of a conditioned rat's fear memory retrieval on a naïve cage-mate's behavior to the conditioned stimulus. We show that rats exposed to a novel tone in the presence of a cage-mate previously conditioned to that same tone selectively showed increased freezing to the stimulus the next day (fear conditioning by-proxy). In addi...

  5. Effects of sleep on memory for conditioned fear and fear extinction

    OpenAIRE

    Pace-Schott, Edward F.; Germain, Anne; Milad, Mohammed R

    2015-01-01

    Learning and memory for extinction of conditioned fear is a basic mammalian mechanism for regulating negative emotion. Sleep promotes both the consolidation of memory and the regulation of emotion. Sleep can influence consolidation and modification of memories associated with both fear and its extinction. After brief overviews of the behavior and neural circuitry associated with fear conditioning, extinction learning and extinction memory in the rodent and human, interactions of sleep with th...

  6. Skin Conductance Fear Conditioning Impairments and Aggression: A Longitudinal Study

    OpenAIRE

    Gao, Yu; Tuvblad, Catherine; Schell, Anne; Baker, Laura; Raine, Adrian

    2014-01-01

    Autonomic fear conditioning deficits have been linked to child aggression and adult criminal behavior. However, it is unknown if fear conditioning deficits are specific to certain subtypes of aggression, and longitudinal research is rare. In the current study, reactive and proactive aggression were assessed in a sample of males and females when aged 10, 12, 15, and 18 years old. Skin conductance fear conditioning data were collected when they were 18 years old. Individuals who were persistent...

  7. Reinstatement of extinguished fear by an unextinguished conditional stimulus

    OpenAIRE

    Halladay, Lindsay R.; Moriel eZelikowsky; Blair, Hugh T.; Fanselow, Michael S.

    2012-01-01

    Anxiety disorders are often treated using extinction-based exposure therapy, but relapse is common and can occur as a result of reinstatement, whereby an aversive trigger can reinstate extinguished fear. Animal models of reinstatement commonly utilize a Pavlovian fear conditioning procedure, in which subjects are first trained to fear a conditional stimulus (CS) by pairing it with an aversive unconditional stimulus (US), and then extinguished by repeated presentations of the CS alone. Reins...

  8. Reinstatement of extinguished fear by an unextinguished conditional stimulus

    OpenAIRE

    Halladay, Lindsay R.; Zelikowsky, Moriel; Blair, Hugh T.; Fanselow, Michael S.

    2012-01-01

    Anxiety disorders are often treated using extinction-based exposure therapy, but relapse is common and can occur as a result of reinstatement, whereby an aversive “trigger” can reinstate extinguished fear. Animal models of reinstatement commonly utilize a Pavlovian fear conditioning procedure, in which subjects are first trained to fear a conditional stimulus (CS) by pairing it with an aversive unconditional stimulus (US), and then extinguished by repeated presentations of the CS alone. Reins...

  9. Fear memory formation can affect a different memory: fear conditioning affects the extinction, but not retrieval, of conditioned taste aversion (CTA) memory

    OpenAIRE

    Joels, Gil; Lamprecht, Raphael

    2014-01-01

    The formation of fear memory to a specific stimulus leads to subsequent fearful response to that stimulus. However, it is not apparent whether the formation of fear memory can affect other memories. We study whether specific fearful experience leading to fear memory affects different memories formation and extinction. We revealed that cued fear conditioning, but not unpaired or naïve training, inhibited the extinction of conditioned taste aversion (CTA) memory that was formed after fear condi...

  10. Rapid amygdala responses during trace fear conditioning without awareness.

    Directory of Open Access Journals (Sweden)

    Nicholas L Balderston

    Full Text Available The role of consciousness in learning has been debated for nearly 50 years. Recent studies suggest that conscious awareness is needed to bridge the gap when learning about two events that are separated in time, as is true for trace fear conditioning. This has been repeatedly shown and seems to apply to other forms of classical conditioning as well. In contrast to these findings, we show that individuals can learn to associate a face with the later occurrence of a shock, even if they are unable to perceive the face. We used a novel application of magnetoencephalography (MEG to non-invasively record neural activity from the amygdala, which is known to be important for fear learning. We demonstrate rapid (∼ 170-200 ms amygdala responses during the stimulus free period between the face and the shock. These results suggest that unperceived faces can serve as signals for impending threat, and that rapid, automatic activation of the amygdala contributes to this process. In addition, we describe a methodology that can be applied in the future to study neural activity with MEG in other subcortical structures.

  11. Developmental aspects of fear: Comparing the acquisition and generalization of conditioned fear in children and adults.

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    Schiele, Miriam A; Reinhard, Julia; Reif, Andreas; Domschke, Katharina; Romanos, Marcel; Deckert, Jürgen; Pauli, Paul

    2016-05-01

    Most research on human fear conditioning and its generalization has focused on adults whereas only little is known about these processes in children. Direct comparisons between child and adult populations are needed to determine developmental risk markers of fear and anxiety. We compared 267 children and 285 adults in a differential fear conditioning paradigm and generalization test. Skin conductance responses (SCR) and ratings of valence and arousal were obtained to indicate fear learning. Both groups displayed robust and similar differential conditioning on subjective and physiological levels. However, children showed heightened fear generalization compared to adults as indexed by higher arousal ratings and SCR to the generalization stimuli. Results indicate overgeneralization of conditioned fear as a developmental correlate of fear learning. The developmental change from a shallow to a steeper generalization gradient is likely related to the maturation of brain structures that modulate efficient discrimination between danger and (ambiguous) safety cues. © 2016 The Authors. Developmental Psychobiology Published by Wiley Periodicals, Inc. Dev Psychobiol 58: 471-481, 2016. PMID:26798984

  12. Specific phobia: a disorder of fear conditioning and extinction.

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    Stein, Dan J; Matsunaga, Hisato

    2006-04-01

    Specific phobia is the most prevalent of the anxiety disorders. Although there have been relatively few studies of its psychobiology and pharmacotherapy, there is a rich laboratory of literature on fear conditioning and extinction and a clear evolutionary perspective. Advances in the cognitive-affective neuroscience of fear processing may ultimately lead to new approaches to the clinical management of phobias. PMID:16641829

  13. Controlled cortical impact before or after fear conditioning does not affect fear extinction in mice.

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    Sierra-Mercado, Demetrio; McAllister, Lauren M; Lee, Christopher C H; Milad, Mohammed R; Eskandar, Emad N; Whalen, Michael J

    2015-05-01

    Post-traumatic stress disorder (PTSD) is characterized in part by impaired extinction of conditioned fear. Traumatic brain injury (TBI) is thought to be a risk factor for development of PTSD. We tested the hypothesis that controlled cortical impact (CCI) would impair extinction of fear learned by Pavlovian conditioning, in mice. To mimic the scenarios in which TBI occurs prior to or after exposure to an aversive event, severe CCI was delivered to the left parietal cortex at one of two time points: (1) Prior to fear conditioning, or (2) after conditioning. Delay auditory conditioning was achieved by pairing a tone with a foot shock in "context A". Extinction training involved the presentation of tones in a different context (context B) in the absence of foot shock. Test for extinction memory was achieved by presentation of additional tones alone in context B over the following two days. In pre- or post-injury paradigms, CCI did not influence fear learning and extinction. Furthermore, CCI did not affect locomotor activity or elevated plus maze testing. Our results demonstrate that, within the time frame studied, CCI does not impair the acquisition and expression of conditioned fear or extinction memory. PMID:25721797

  14. Psychopaths show enhanced amygdala activation during fear conditioning

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    Douglas eSchultz

    2016-03-01

    Full Text Available Psychopathy is a personality disorder characterized by emotional deficits and a failure to inhibit impulsive behavior and is often subdivided into primary and secondary psychopathic subtypes. The maladaptive behavior related to primary psychopathy is thought to reflect constitutional fearlessness, while the problematic behavior related to secondary psychopathy is motivated by other factors. The fearlessness observed in psychopathy has often been interpreted as reflecting a fundamental deficit in amygdala function, and previous studies have provided support for a low-fear model of psychopathy. However, many of these studies fail to use appropriate screening procedures, use liberal inclusion criteria, or have used unconventional approaches to assay amygdala function. We measured brain activity with BOLD imaging in primary and secondary psychopaths and non-psychopathic control subjects during Pavlovian fear conditioning. In contrast to the low-fear model, we observed normal fear expression in primary psychopaths. Psychopaths also displayed greater differential BOLD activity in the amygdala relative to matched controls. Inverse patterns of activity were observed in the anterior cingulate cortex (ACC for primary versus secondary psychopaths. Primary psychopaths exhibited a pattern of activity in the dorsal and ventral ACC consistent with enhanced fear expression, while secondary psychopaths exhibited a pattern of activity in these regions consistent with fear inhibition. These results contradict the low-fear model of psychopathy and suggest that the low fear observed for psychopaths in previous studies may be specific to secondary psychopaths.

  15. An Appetitive Conditioned Stimulus Enhances Fear Acquisition and Impairs Fear Extinction

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    Leung, Hiu T.; Holmes, Nathan M.; Westbrook, R. Frederick

    2016-01-01

    Four experiments used between- and within-subject designs to examine appetitive-aversive interactions in rats. Experiments 1 and 2 examined the effect of an excitatory appetitive conditioned stimulus (CS) on acquisition and extinction of conditioned fear. In Experiment 1, a CS shocked in a compound with an appetitive excitor (i.e., a stimulus…

  16. Categories, Concepts, and Conditioning: How Humans Generalize Fear

    OpenAIRE

    Dunsmoor, Joseph E.; Murphy, Gregory L

    2015-01-01

    During the past century, Pavlovian conditioning has served as the predominant experimental paradigm and theoretical framework to understand how humans learn to fear and avoid real or perceived dangers. Animal models for translational research offer insight into basic behavioral and neurophysiological factors mediating the acquisition, expression, inhibition, and generalization of fear. However, it is important to consider the limits of traditional animal models when applied to humans. Here, w...

  17. Characterization of fear conditioning and fear extinction by analysis of electrodermal activity.

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    Faghih, Rose T; Stokes, Patrick A; Marin, Marie-France; Zsido, Rachel G; Zorowitz, Sam; Rosenbaum, Blake L; Huijin Song; Milad, Mohammed R; Dougherty, Darin D; Eskandar, Emad N; Widge, Alik S; Brown, Emery N; Barbieri, Riccardo

    2015-08-01

    Electrodermal activity (EDA) is a measure of physical arousal, which is frequently measured during psychophysical tasks relevant for anxiety disorders. Recently, specific protocols and procedures have been devised in order to examine the neural mechanisms of fear conditioning and extinction. EDA reflects important responses associated with stimuli specifically administrated during these procedures. Although several previous studies have demonstrated the reproducibility of measures estimated from EDA, a mathematical framework associated with the stimulus-response experiments in question and, at the same time, including the underlying emotional state of the subject during fear conditioning and/or extinction experiments is not well studied. We here propose an ordinary differential equation model based on sudomotor nerve activity, and estimate the fear eliciting stimulus using a compressed sensing algorithm. Our results show that we are able to recover the underlying stimulus (visual cue or mild electrical shock). Moreover, relating the time-delay in the estimated stimulation to the visual cue during extinction period shows that fear level decreases as visual cues are presented without shock, suggesting that this feature might be used to estimate the fear state. These findings indicate that a mathematical model based on electrodermal responses might be critical in defining a low-dimensional representation of essential cognitive features in order to describe dynamic behavioral states. PMID:26738104

  18. Anterograde effects of a single electroconvulsive shock on inhibitory avoidance and on cued fear conditioning

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    Oliveira M.G.M.

    1998-01-01

    Full Text Available A single electroconvulsive shock (ECS or a sham ECS was administered to male 3-4-month-old Wistar rats 1, 2, and 4 h before training in an inhibitory avoidance test and in cued classical fear conditioning (measured by means of freezing time in a new environment. ECS impaired inhibitory avoidance at all times and, at 1 or 2 h before training, reduced freezing time before and after re-presentation of the ECS. These results are interpreted as a transient conditioned stimulus (CS-induced anxiolytic or analgesic effect lasting about 2 h after a single treatment, in addition to the known amnesic effect of the stimulus. This suggests that the effect of anterograde learning impairment is demonstrated unequivocally only when the analgesic/anxiolytic effect is over (about 4 h after ECS administration and that this impairment of learning is selective, affecting inhibitory avoidance but not classical fear conditioning to a discrete stimulus.

  19. Prior fear conditioning and reward learning interact in fear and reward networks

    Directory of Open Access Journals (Sweden)

    Dominik R Bach

    2014-03-01

    Full Text Available The ability to flexibly adapt responses to changes in the environment is important for survival. Previous research in humans separately examined the mechanisms underlying acquisition and extinction of aversive and appetitive conditioned responses. It is yet unclear how aversive and appetitive learning interact on a neural level during counterconditioning in humans. This functional magnetic resonance imaging (fMRI study investigated the interaction of fear conditioning and subsequent reward learning. In the first phase (fear acquisition, images predicted aversive electric shocks or no aversive outcome. In the second phase (counterconditioning, half of the CS+ and CS- were associated with monetary reward in the absence of electric stimulation. The third phase initiated reinstatement of fear through presentation of electric shocks, followed by CS presentation in the absence of shock or reward. Results indicate that participants were impaired at learning the reward contingencies for stimuli previously associated with shock. In the counterconditioning phase, prior fear association interacted with reward representation in the amygdala, where activation was decreased for rewarded compared to unrewarded CS- trials, while there was no reward-related difference in CS+ trials. In the reinstatement phase, an interaction of previous fear association and previous reward status was observed in a reward network consisting of substantia nigra / ventral tegmental area (SN/VTA, striatum and orbitofrontal cortex (OFC, where activation was increased by previous reward association only for CS- but not for CS+ trials. These findings suggest that during counterconditioning, prior fear conditioning interferes with reward learning, subsequently leading to lower activation of the reward network.

  20. Effects of sleep on memory for conditioned fear and fear extinction.

    Science.gov (United States)

    Pace-Schott, Edward F; Germain, Anne; Milad, Mohammed R

    2015-07-01

    Learning and memory for extinction of conditioned fear is a basic mammalian mechanism for regulating negative emotion. Sleep promotes both the consolidation of memory and the regulation of emotion. Sleep can influence consolidation and modification of memories associated with both fear and its extinction. After brief overviews of the behavior and neural circuitry associated with fear conditioning, extinction learning, and extinction memory in the rodent and human, interactions of sleep with these processes will be examined. Animal and human studies suggest that sleep can serve to consolidate both fear and extinction memory. In humans, sleep also promotes generalization of extinction memory. Time-of-day effects on extinction learning and generalization are also seen. Rapid eye movement (REM) may be a sleep stage of particular importance for the consolidation of both fear and extinction memory as evidenced by selective REM deprivation experiments. REM sleep is accompanied by selective activation of the same limbic structures implicated in the learning and memory of fear and extinction. Preliminary evidence also suggests extinction learning can take place during slow wave sleep. Study of low-level processes such as conditioning, extinction, and habituation may allow sleep effects on emotional memory to be identified and inform study of sleep's effects on more complex, emotionally salient declarative memories. Anxiety disorders are marked by impairments of both sleep and extinction memory. Improving sleep quality may ameliorate anxiety disorders by strengthening naturally acquired extinction. Strategically timed sleep may be used to enhance treatment of anxiety by strengthening therapeutic extinction learned via exposure therapy. (PsycINFO Database Record PMID:25894546

  1. Reprint of: "Demographic factors predict magnitude of conditioned fear".

    Science.gov (United States)

    Rosenbaum, Blake L; Bui, Eric; Marin, Marie-France; Holt, Daphne J; Lasko, Natasha B; Pitman, Roger K; Orr, Scott P; Milad, Mohammed R

    2015-12-01

    There is substantial variability across individuals in the magnitudes of their skin conductance (SC) responses during the acquisition and extinction of conditioned fear. To manage this variability, subjects may be matched for demographic variables, such as age, gender and education. However, limited data exist addressing how much variability in conditioned SC responses is actually explained by these variables. The present study assessed the influence of age, gender and education on the SC responses of 222 subjects who underwent the same differential conditioning paradigm. The demographic variables were found to predict a small but significant amount of variability in conditioned responding during fear acquisition, but not fear extinction learning or extinction recall. A larger differential change in SC during acquisition was associated with more education. Older participants and women showed smaller differential SC during acquisition. Our findings support the need to consider age, gender and education when studying fear acquisition but not necessarily when examining fear extinction learning and recall. Variability in demographic factors across studies may partially explain the difficulty in reproducing some SC findings. PMID:26608179

  2. Voluntary exercise during extinction of auditory fear conditioning reduces the relapse of fear associated with potentiated activity of striatal direct pathway neurons.

    Science.gov (United States)

    Mika, Agnieszka; Bouchet, Courtney A; Bunker, Preston; Hellwinkel, Justin E; Spence, Katie G; Day, Heidi E W; Campeau, Serge; Fleshner, Monika; Greenwood, Benjamin N

    2015-11-01

    Relapse of previously extinguished fear presents a significant, pervasive obstacle to the successful long-term treatment of anxiety and trauma-related disorders. Thus, identification of a novel means to enhance fear extinction to stand the passage of time and generalize across contexts is of the utmost importance. Acute bouts of exercise can be used as inexpensive, noninvasive treatment strategies to reduce anxiety, and have been shown to enhance memory for extinction when performed in close temporal proximity to the extinction session. However, it is unclear whether acute exercise can be used to prevent relapse of fear, and the neural mechanisms underlying this potential effect are unknown. The current study therefore examined whether acute exercise during extinction of auditory fear can protect against the later relapse of fear. Male F344 rats lacking an extended history of wheel running were conditioned to fear a tone CS and subsequently extinguished within either a freely mobile running wheel, a locked wheel, or a control context lacking a wheel. Rats exposed to fear extinction within a freely mobile wheel ran during fear extinction, and demonstrated reduced fear as well as attenuated corticosterone levels during re-exposure to the extinguished CS during the relapse test in a novel context 1week later. Examination of cfos mRNA patterns elicited by re-exposure to the extinguished CS during the relapse test revealed that acute exercise during extinction decreased activation of brain circuits classically involved in driving fear expression and interestingly, increased activity within neurons of the direct striatal pathway involved in reward signaling. These data suggest that exercise during extinction reduces relapse through a mechanism involving the direct pathway of the striatum. It is suggested that a positive affective state could become associated with the CS during exercise during extinction, thus resulting in a relapse-resistant extinction memory. PMID

  3. Sex Differences in Response to an Observational Fear Conditioning Procedure

    Science.gov (United States)

    Kelly, Megan M.; Forsyth, John P.

    2007-01-01

    The present study evaluated sex differences in observational fear conditioning using modeled ''mock'' panic attacks as an unconditioned stimulus (UCS). Fifty-nine carefully prescreened healthy undergraduate participants (30 women) underwent 3 consecutive differential conditioning phases: habituation, acquisition, and extinction. It was expected…

  4. Enhanced Generalization of Auditory Conditioned Fear in Juvenile Mice

    Science.gov (United States)

    Ito, Wataru; Pan, Bing-Xing; Yang, Chao; Thakur, Siddarth; Morozov, Alexei

    2009-01-01

    Increased emotionality is a characteristic of human adolescence, but its animal models are limited. Here we report that generalization of auditory conditioned fear between a conditional stimulus (CS+) and a novel auditory stimulus is stronger in 4-5-wk-old mice (juveniles) than in their 9-10-wk-old counterparts (adults), whereas nonassociative…

  5. Medial prefrontal cortex stimulation modulates the processing of conditioned fear

    Directory of Open Access Journals (Sweden)

    Anne Guhn

    2014-02-01

    Full Text Available The extinction of conditioned fear is dependent on an efficient interplay between the amygdala and the medial prefrontal cortex (mPFC. In rats, high-frequency electrical mPFC stimulation was shown to improve extinction by a reduction of amygdala activity. However, so far it is unclear whether stimulation of homologues regions in humans might have similar beneficial effects.Healthy volunteers received one-session of either active or sham repetitive transcranial magnetic stimulation (rTMS covering the mPFC while undergoing a two-day fear conditioning and extinction paradigm. rTMS was applied offline after fear acquisition in which one of two faces (CS+ but not CS- was associated with an aversive scream (UCS. Immediate extinction learning (day 1 and extinction recall (day 2 were conducted without UCS delivery. Conditioned responses were assessed in a multimodal approach using fear-potentiated startle (FPS, skin conductance responses (SCR, functional near-infrared spectroscopy (fNIRS and self-report scales. Consistent with the hypothesis of a modulated processing of conditioned fear after high-frequency rTMS, the active group showed a reduced CS+/CS- discrimination during extinction learning as evident in FPS as well as in SCR and arousal ratings. FPS responses to CS+ further showed a linear decrement throughout both extinction sessions. This study describes the first experimental approach of influencing conditioned fear by using rTMS which can be a basis for future studies investigating a complementation of mPFC stimulation to cognitive behavioral therapy.

  6. Blockade of endogenous opioid neurotransmission enhances acquisition of conditioned fear in humans.

    Science.gov (United States)

    Eippert, Falk; Bingel, Ulrike; Schoell, Eszter; Yacubian, Juliana; Büchel, Christian

    2008-05-21

    The endogenous opioid system is involved in fear learning in rodents, as opioid agonists attenuate and opioid antagonists facilitate the acquisition of conditioned fear. It has been suggested that an opioidergic signal, which is engaged through conditioning and acts inhibitory on unconditioned stimulus input, is the source of these effects. To clarify whether blockade of endogenous opioid neurotransmission enhances acquisition of conditioned fear in humans, and to elucidate the neural underpinnings of such an effect, we used functional magnetic resonance imaging in combination with behavioral recordings and a double-blind pharmacological intervention. All subjects underwent the same classical fear-conditioning paradigm, but subjects in the experimental group received the opioid antagonist naloxone before and during the experiment, in contrast to subjects in the control group, who received saline. Blocking endogenous opioid neurotransmission with naloxone led to more sustained responses to the unconditioned stimulus across trials, evident in both behavioral and blood oxygen level-dependent responses in pain responsive cortical regions. This effect was likely caused by naloxone blocking conditioned responses in a pain-inhibitory circuit involving opioid-rich areas such as the rostral anterior cingulate cortex, amygdala, and periaqueductal gray. Most importantly, naloxone enhanced the acquisition of fear on the behavioral level and changed the activation profile of the amygdala: whereas the control group showed rapidly decaying conditioned responses across trials, the naloxone group showed sustained conditioned responses in the amygdala. Together, these results demonstrate that in humans the endogenous opioid system has an inhibitory role in the acquisition of fear. PMID:18495880

  7. Ethnic differences in physiological responses to fear conditioned stimuli.

    Science.gov (United States)

    Martínez, Karen G; Franco-Chaves, José A; Milad, Mohammed R; Quirk, Gregory J

    2014-01-01

    The idea that emotional expression varies with ethnicity is based largely on questionnaires and behavioral observations rather than physiological measures. We therefore compared the skin conductance responses (SCR) of Hispanic (Puerto Rican) and White non-Hispanic subjects in a fear conditioning and fear extinction task. Subjects were recruited from two sites: San Juan, Puerto Rico (PR), and Boston, Massachusetts (MA), using identical methods. A total of 78 healthy subjects (39 from PR, 39 from MA) were divided by sex and matched for age and educational level. Females from the two sites did not differ in their SCRs during any experimental phase of fear conditioning (habituation, conditioning, or extinction). In contrast, PR males responded significantly to the conditioned stimulus than MA males or PR females. Subtracting ethnic differences observed during the habituation phase (prior to conditioning) eliminated differences from subsequent phases, suggesting that PR males are elevated in their response to novelty rather than fear learning. Our findings suggest that, in addition to sex differences, there are ethnic differences in physiological responses to novel stimuli at least in males, which could be relevant for the assessment and treatment of anxiety disorders. PMID:25501365

  8. Ethnic differences in physiological responses to fear conditioned stimuli.

    Directory of Open Access Journals (Sweden)

    Karen G Martínez

    Full Text Available The idea that emotional expression varies with ethnicity is based largely on questionnaires and behavioral observations rather than physiological measures. We therefore compared the skin conductance responses (SCR of Hispanic (Puerto Rican and White non-Hispanic subjects in a fear conditioning and fear extinction task. Subjects were recruited from two sites: San Juan, Puerto Rico (PR, and Boston, Massachusetts (MA, using identical methods. A total of 78 healthy subjects (39 from PR, 39 from MA were divided by sex and matched for age and educational level. Females from the two sites did not differ in their SCRs during any experimental phase of fear conditioning (habituation, conditioning, or extinction. In contrast, PR males responded significantly to the conditioned stimulus than MA males or PR females. Subtracting ethnic differences observed during the habituation phase (prior to conditioning eliminated differences from subsequent phases, suggesting that PR males are elevated in their response to novelty rather than fear learning. Our findings suggest that, in addition to sex differences, there are ethnic differences in physiological responses to novel stimuli at least in males, which could be relevant for the assessment and treatment of anxiety disorders.

  9. Classical conditioned responses to absent tones

    OpenAIRE

    Häusler Udo; Jürgens Uwe; Bangert Marc; Altenmüller Eckart

    2006-01-01

    Abstract Background Recent evidence for a tight coupling of sensorimotor processes in trained musicians led to the question of whether this coupling extends to preattentively mediated reflexes; particularly, whether a classically conditioned response in one of the domains (auditory) is generalized to another (tactile/motor) on the basis of a prior association in a second-order Pavlovian paradigm. An eyeblink conditioning procedure was performed in 17 pianists, serving as a model for overlearn...

  10. Estrous cycle phase and gonadal hormones influence conditioned fear extinction

    Science.gov (United States)

    Milad, Mohammed R; Igoe, Sarah A; Lebron-Milad, Kelimer; Novales, Juan E

    2009-01-01

    Gonadal hormones modulate fear acquisition, but less is known about the influence of gonadal hormones on fear extinction. We assessed sex differences and the influence of gonadal hormone fluctuations and exogenous manipulations of estrogen and progesterone on acquisition, extinction learning and extinction recall in a 3-day auditory fear conditioning and extinction protocol. Experiments were conducted on males and naturally cycling female rats. Regarding female rats, significant differences in fear extinction were observed between subgroups of females, depending on their phase of the estrous cycle. Extinction that took place during the proestrus (high estrogen/progesterone) phase was more fully consolidated, as evidenced by low freezing during a recall test. This suggests that estrogen and/or progesterone facilitate extinction. In support of this, injection of both estrogen and progesterone prior to extinction learning in female rats during the metestrus phase of the cycle (low estrogen/progesterone) facilitated extinction consolidation, and blockade of estrogen and progesterone receptors during the proestrus phase impaired extinction consolidation. When comparing male to female rats without consideration of the estrous cycle phase, no significant sex differences were observed. When accounting for cycle phase in females, sex differences were observed only during extinction recall. Female rats that underwent extinction during the metestrus phase showed significantly higher freezing during the recall test relative to males. Collectively, these data suggest that gonadal hormones influence extinction behavior possibly by influencing the function of brain regions involved in the consolidation of fear extinction. Moreover, the elevated fear observed in female relative to male rats during extinction recall suggests that gonadal hormones may in part play a role in the higher prevalence of anxiety disorders in women. PMID:19761818

  11. FAAH inhibitor OL-135 disrupts contextual, but not auditory, fear conditioning in rats.

    Science.gov (United States)

    Burman, Michael A; Szolusha, Kerribeth; Bind, Rebecca; Kerney, Kristen; Boger, Dale L; Bilsky, Edward J

    2016-07-15

    Anxiety disorders are among the most prevalent psychological disorders, have significant negative impacts on quality of life and the healthcare system, and yet effective treatments remain elusive. Manipulating the endocannabinoid system has demonstrated potential for treating anxiety, although the side effects of direct manipulations of cannabinoid receptors keeps them from widespread clinical use. Disrupting the degradation enzyme fatty acid amide hydrolase (FAAH) enhances endogenous signaling and may produce similar efficacy without the side effects. The current experiments examine the effects of low (5.6mg/kg) or moderate (10.0mg/kg) doses of OL-135, a FAAH inhibitor, on the acquisition and consolidation of classical fear conditioning, a common model of trauma-induced anxiety. The acquisition of contextual, but not auditory, fear conditioning was disrupted by both doses of OL-135. Shock reactivity was not affected. Due to the additional neural circuitry required for contextual, but not auditory, fear conditioning, these data suggest that endocannabinoid signaling outside the amygdala may be critical for a subset of fearful memories. PMID:27083303

  12. Controllable versus uncontrollable stressors bi-directionally modulate conditioned but not innate fear.

    Science.gov (United States)

    Baratta, M V; Christianson, J P; Gomez, D M; Zarza, C M; Amat, J; Masini, C V; Watkins, L R; Maier, S F

    2007-06-01

    Fear conditioning and fear extinction play key roles in the development and treatment of anxiety-related disorders, yet there is little information concerning experiential variables that modulate these processes. Here we examined the impact of exposure to a stressor in a different environment on subsequent fear conditioning and extinction, and whether the degree of behavioral control that the subject has over the stressor is of importance. Rats received a session of either escapable (controllable) tail shock (ES), yoked inescapable (uncontrollable) tail shock (IS), or control treatment (home cage, HC) 7 days before fear conditioning in which a tone and foot shock were paired. Conditioning was measured 24 h later. In a second experiment rats received ES, IS or HC 24 h after contextual fear conditioning. Extinction then occurred every day beginning 7 days later until a criterion was reached. Spontaneous recovery of fear was assessed 14 days after extinction. IS potentiated fear conditioning when given before fear conditioning, and potentiated fear responding during extinction when given after conditioning. Importantly, ES potently interfered with later fear conditioning, decreased fear responding during fear extinction, and prevented spontaneous recovery of fear. Additionally, we examined if the activation of the ventral medial prefrontal cortex (mPFCv) by ES is critical for the protective effects of ES on later fear conditioning. Inactivation of the mPFCv with muscimol at the time of the initial experience with control prevented ES-induced reductions in later contextual and auditory fear conditioning. Finally, we explored if the protective effects of ES extended to an unconditioned fear stimulus, ferret odor. Unlike conditioned fear, prior ES increased the fear response to ferret odor to the same degree as did IS. PMID:17478046

  13. Fear-potentiation in the elevated plus-maze test depends on stressor controllability and fear conditioning

    NARCIS (Netherlands)

    Korte, S M; Bohus, B; de Boer, Sietse

    1999-01-01

    The purpose of the study was to determine which stressor qualities (escapable vs. inescapable stress and unconditioned vs. conditioned stress) can potentiate fear in the elevated plus-maze. While inescapable stress potentiated fear, escapable stress did not, but escapable stress increased the locomo

  14. Coantagonism of glutamate receptors and nicotinic acetylcholinergic receptors disrupts fear conditioning and latent inhibition of fear conditioning

    OpenAIRE

    Gould, Thomas J.; Lewis, Michael C.

    2005-01-01

    The present study investigated the hypothesis that both nicotinic acetylcholinergic receptors (nAChRs) and glutamate receptors (α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors (AMPARs) and N-methyl-d-aspartate glutamate receptors (NMDARs)) are involved in fear conditioning, and may modulate similar processes. The effects of the nAChR antagonist mecamylamine administered alone, the AMPAR antagonist NBQX administered alone, and the NMDAR antagonist MK-801 administered alone on cued ...

  15. Resting heart rate variability predicts safety learning and fear extinction in an interoceptive fear conditioning paradigm.

    Directory of Open Access Journals (Sweden)

    Meike Pappens

    Full Text Available This study aimed to investigate whether interindividual differences in autonomic inhibitory control predict safety learning and fear extinction in an interoceptive fear conditioning paradigm. Data from a previously reported study (N = 40 were extended (N = 17 and re-analyzed to test whether healthy participants' resting heart rate variability (HRV - a proxy of cardiac vagal tone - predicts learning performance. The conditioned stimulus (CS was a slight sensation of breathlessness induced by a flow resistor, the unconditioned stimulus (US was an aversive short-lasting suffocation experience induced by a complete occlusion of the breathing circuitry. During acquisition, the paired group received 6 paired CS-US presentations; the control group received 6 explicitly unpaired CS-US presentations. In the extinction phase, both groups were exposed to 6 CS-only presentations. Measures included startle blink EMG, skin conductance responses (SCR and US-expectancy ratings. Resting HRV significantly predicted the startle blink EMG learning curves both during acquisition and extinction. In the unpaired group, higher levels of HRV at rest predicted safety learning to the CS during acquisition. In the paired group, higher levels of HRV were associated with better extinction. Our findings suggest that the strength or integrity of prefrontal inhibitory mechanisms involved in safety- and extinction learning can be indexed by HRV at rest.

  16. De Novo Fear Conditioning Across Diagnostic Groups in the Affective Disorders: Evidence for Learning Impairments

    OpenAIRE

    Otto, Michael W; Moshier, Samantha J; Kinner, Dina G.; Simon, Naomi M.; Pollack, Mark H.; Orr, Scott P

    2014-01-01

    De novo fear conditioning paradigms have served as a model for how clinical anxiety may be acquired and maintained. To further examine variable findings in the acquisition and extinction of fear responses between clinical and non-clinical samples, we assessed de novo fear conditioning outcomes in outpatients with either anxiety disorders or depression and healthy subjects recruited from the community. Overall, we found evidence for attenuated fear conditioning, as measured by skin conductance...

  17. Resistance to extinction in human fear learning, an ERP investigation of procedural and fear relevance effects on conditioned responding

    OpenAIRE

    Ugland, Carina C O

    2011-01-01

    In human fear conditioning 'resistance to extinction' occurs when the removal of the aversive outcome fails to produce a reduction in conditioned responding. This phenomenon is important to understanding the persistence of anxiety disorders such as phobias. The research presented in this thesis examines factors that promote the acquisition and maintenance of learned fear response and attempts to differentiate between different explanations of the resistance to extinction phenomenon. To inv...

  18. Fear but not fright: re-evaluating traumatic experience attenuates anxiety-like behaviors after fear conditioning

    Directory of Open Access Journals (Sweden)

    Marco eCostanzi

    2014-08-01

    Full Text Available Fear allows organisms to cope with dangerous situations and remembering these situations has an adaptive role preserving individuals from injury and death. However, recalling traumatic memories can induce re-experiencing the trauma, thus resulting in a maladaptive fear. A failure to properly regulate fear responses has been associated with anxiety disorders, like Posttraumatic Stress Disorder (PTSD. Thus, re-establishing the capability to regulate fear has an important role for its adaptive and clinical relevance. Strategies aimed at erasing fear memories have been proposed, although there are limits about their efficiency in treating anxiety disorders. To re-establish fear regulation, here we propose a new approach, based on the re-evaluation of the aversive value of traumatic experience. Mice were submitted to a contextual-fear-conditioning paradigm in which a neutral context was paired with an intense electric footshock. Three weeks after acquisition, conditioned mice were treated with a less intense footshock (pain threshold. The effectiveness of this procedure in reducing fear expression was assessed in terms of behavioral outcomes related to PTSD (e.g. hyper-reactivity to a neutral tone, anxiety levels in a plus maze task, social avoidance, and learning deficits in a spatial water maze and of amygdala activity by evaluating c-fos expression. Furthermore, a possible role of lateral orbitofrontal cortex (lOFC in mediating the behavioral effects induced by the re-evaluation procedure was investigated. We observed that this treatment (i significantly mitigates the abnormal behavioral outcomes induced by trauma, (ii persistently attenuates fear expression without erasing contextual memory, (iii prevents fear reinstatement, (iv reduces amygdala activity and (v requires an intact lOFC to be effective.The results suggest that an effective strategy to treat pathological anxiety should address cognitive re-evaluation of traumatic experiences

  19. Fear-Conditioning Mechanisms Associated with Trait Vulnerability to Anxiety in Humans

    OpenAIRE

    Indovina, Iole; Robbins, Trevor W.; Núñez-Elizalde, Anwar O.; Dunn, Barnaby D.; Bishop, Sonia J.

    2011-01-01

    Summary Investigations of fear conditioning in rodents and humans have illuminated the neural mechanisms underlying cued and contextual fear. A critical question is how personality dimensions such as trait anxiety act through these mechanisms to confer vulnerability to anxiety disorders, and whether humans' ability to overcome acquired fears depends on regulatory skills not characterized in animal models. In a neuroimaging study of fear conditioning in humans, we found evidence for two indepe...

  20. Individual differences in discriminatory fear learning under conditions of ambiguity: A vulnerability factor for anxiety disorders?

    OpenAIRE

    TomBeckers

    2013-01-01

    Complex fear learning procedures might be better suited than the common differential fear conditioning paradigm for detecting individual differences related to vulnerability for anxiety disorders. Two such procedures are the blocking procedure and the protection-from-overshadowing procedure. Their comparison allows for the examination of discriminatory fear learning under conditions of ambiguity. The present study examined the role of individual differences in such discriminatory fear learnin...

  1. Individual Differences in Discriminatory Fear Learning under Conditions of Ambiguity: A Vulnerability Factor for Anxiety Disorders?

    OpenAIRE

    Arnaudova, Inna; Krypotos, Angelos-Miltiadis; Effting, Marieke; Boddez, Yannick; Kindt, Merel; Beckers, Tom

    2013-01-01

    Complex fear learning procedures might be better suited than the common differential fear-conditioning paradigm for detecting individual differences related to vulnerability for anxiety disorders. Two such procedures are the blocking procedure and the protection-from-overshadowing procedure. Their comparison allows for the examination of discriminatory fear learning under conditions of ambiguity. The present study examined the role of individual differences in such discriminatory fear learnin...

  2. Sleep Promotes Generalization of Extinction of Conditioned Fear

    Science.gov (United States)

    Pace-Schott, Edward F.; Milad, Mohammed R.; Orr, Scott P.; Rauch, Scott L.; Stickgold, Robert; Pitman, Roger K.

    2009-01-01

    Study Objective: To examine the effects of sleep on fear conditioning, extinction, extinction recall, and generalization of extinction recall in healthy humans. Design: During the Conditioning phase, a mild, 0.5-sec shock followed conditioned stimuli (CS+s), which consisted of 2 differently colored lamps. A third lamp color was interspersed but never reinforced (CS-). Immediately after Conditioning, one CS+ was extinguished (CS+E) by presentation without shocks (Extinction phase). The other CS+ went unextinguished (CS+U). Twelve hours later, following continuous normal daytime waking (Wake group, N = 27) or an equal interval containing a normal night's sleep (Sleep group, N = 26), conditioned responses (CRs) to all CSs were measured (Extinction Recall phase). It was hypothesized that the Sleep versus Wake group would show greater extinction recall and/or generalization of extinction recall from the CS+E to the CS+U. Setting: Academic medical center. Subjects: Paid normal volunteers. Measurements and Results: Square-root transformed skin conductance response (SCR) measured conditioned responding. During Extinction Recall, the Group (Wake or Sleep) × CS+ Type (CS+E or CS+U) interaction was significant (P = 0.04). SCRs to the CS+E did not differ between groups, whereas SCRs to the CS+U were significantly smaller in the Sleep group. Additionally, SCRs were significantly larger to the CS+U than CS+E in the Wake but not the Sleep group. Conclusions: After sleep, extinction memory generalized from an extinguished conditioned stimulus to a similarly conditioned but unextinguished stimulus. Clinically, adequate sleep may promote generalization of extinction memory from specific stimuli treated during exposure therapy to similar stimuli later encountered in vivo. Citation: Pace-Schott EF; Milad MR; Orr SP; Rauch SL; Stickgold R; Pitman RK. Sleep promotes generalization of extinction of conditioned fear. SLEEP 2009;32(1):19-26. PMID:19189775

  3. Early Extinction after Fear Conditioning Yields a Context-Independent and Short-Term Suppression of Conditional Freezing in Rats

    Science.gov (United States)

    Chang, Chun-hui; Maren, Stephen

    2009-01-01

    Extinction of Pavlovian fear conditioning in rats is a useful model for therapeutic interventions in humans with anxiety disorders. Recently, we found that delivering extinction trials soon (15 min) after fear conditioning yields a short-term suppression of fear, but little long-term extinction. Here, we explored the possible mechanisms underlying…

  4. Mindfulness-Based Stress Reduction, Fear Conditioning, and The Uncinate Fasciculus: A Pilot Study.

    Science.gov (United States)

    Hölzel, Britta K; Brunsch, Vincent; Gard, Tim; Greve, Douglas N; Koch, Kathrin; Sorg, Christian; Lazar, Sara W; Milad, Mohammed R

    2016-01-01

    Mindfulness has been suggested to impact emotional learning, but research on these processes is scarce. The classical fear conditioning/extinction/extinction retention paradigm is a well-known method for assessing emotional learning. The present study tested the impact of mindfulness training on fear conditioning and extinction memory and further investigated whether changes in white matter fiber tracts might support such changes. The uncinate fasciculus (UNC) was of particular interest in the context of emotional learning. In this pilot study, 46 healthy participants were quasi-randomized to a Mindfulness-Based Stress Reduction (MBSR, N = 23) or waitlist control (N = 23) group and underwent a two-day fear conditioning, extinction learning, and extinction memory protocol before and after the course or control period. Skin conductance response (SCR) data served to measure the physiological response during conditioning and extinction memory phases. Diffusion tensor imaging (DTI) data were analyzed with probabilistic tractography and analyzed for changes of fractional anisotropy in the UNC. During conditioning, participants were able to maintain a differential response to conditioned vs. not conditioned stimuli following the MBSR course (i.e., higher sensitivity to the conditioned stimuli), while controls dropped the response. Extinction memory results were not interpretable due to baseline differences. MBSR participants showed a significant increase in fractional anisotropy in the UNC, while controls did not (group by time interaction missed significance). Pre-post changes in UNC were correlated with changes in the response to the conditioned stimuli. The findings suggest effects of mindfulness practice on the maintenance of sensitivity of emotional responses and suggest underlying neural plasticity. (ClinicalTrials.gov, Identifier NCT01320969, https://clinicaltrials.gov/ct2/show/NCT01320969). PMID:27378875

  5. Mindfulness-Based Stress Reduction, Fear Conditioning, and The Uncinate Fasciculus: A Pilot Study

    Science.gov (United States)

    Hölzel, Britta K.; Brunsch, Vincent; Gard, Tim; Greve, Douglas N.; Koch, Kathrin; Sorg, Christian; Lazar, Sara W.; Milad, Mohammed R.

    2016-01-01

    Mindfulness has been suggested to impact emotional learning, but research on these processes is scarce. The classical fear conditioning/extinction/extinction retention paradigm is a well-known method for assessing emotional learning. The present study tested the impact of mindfulness training on fear conditioning and extinction memory and further investigated whether changes in white matter fiber tracts might support such changes. The uncinate fasciculus (UNC) was of particular interest in the context of emotional learning. In this pilot study, 46 healthy participants were quasi-randomized to a Mindfulness-Based Stress Reduction (MBSR, N = 23) or waitlist control (N = 23) group and underwent a two-day fear conditioning, extinction learning, and extinction memory protocol before and after the course or control period. Skin conductance response (SCR) data served to measure the physiological response during conditioning and extinction memory phases. Diffusion tensor imaging (DTI) data were analyzed with probabilistic tractography and analyzed for changes of fractional anisotropy in the UNC. During conditioning, participants were able to maintain a differential response to conditioned vs. not conditioned stimuli following the MBSR course (i.e., higher sensitivity to the conditioned stimuli), while controls dropped the response. Extinction memory results were not interpretable due to baseline differences. MBSR participants showed a significant increase in fractional anisotropy in the UNC, while controls did not (group by time interaction missed significance). Pre-post changes in UNC were correlated with changes in the response to the conditioned stimuli. The findings suggest effects of mindfulness practice on the maintenance of sensitivity of emotional responses and suggest underlying neural plasticity. (ClinicalTrials.gov, Identifier NCT01320969, https://clinicaltrials.gov/ct2/show/NCT01320969). PMID:27378875

  6. Double Dissociation of Amygdala and Hippocampal Contributions to Trace and Delay Fear Conditioning

    OpenAIRE

    Raybuck, Jonathan D.; Lattal, K. Matthew

    2011-01-01

    A key finding in studies of the neurobiology of learning memory is that the amygdala is critically involved in Pavlovian fear conditioning. This is well established in delay-cued and contextual fear conditioning; however, surprisingly little is known of the role of the amygdala in trace conditioning. Trace fear conditioning, in which the CS and US are separated in time by a trace interval, requires the hippocampus and prefrontal cortex. It is possible that recruitment of cortical structures b...

  7. Avoiding negative outcomes: tracking the mechanisms of avoidance learning in humans during fear conditioning

    Directory of Open Access Journals (Sweden)

    Mauricio R Delgado

    2009-11-01

    Full Text Available Previous research across species has shown that the amygdala is critical for learning about aversive outcomes, while the striatum is involved in reward-related processing. Less is known, however, about the role of the amygdala and the striatum in learning how to exert control over emotions and avoid negative outcomes. One potential mechanism for active avoidance of stressful situations is postulated to involve amygdala-striatal interactions. The goal of this study was to investigate the physiological and neural correlates underlying avoidance learning in humans. Specifically, we used a classical conditioning paradigm where three different conditioned stimuli (CS were presented. One stimulus predicted the delivery of a shock upon stimulus offset (CS+, while another predicted no negative consequences (CS-. A third conditioned cue also predicted delivery of a shock, but participants were instructed that upon seeing this stimulus, they could avoid the shock if they chose the correct action (AV +. After successful learning, participants could then easily terminate the shock during subsequent stimulus presentations (AV-. Physiological responses (as measured by SCRs confirmed a main effect of conditioning, particularly showing higher arousal responses during pre (AV+ compared to post (AV- learning of an avoidance response. Consistent with animal models, amygdala-striatal interactions were observed to underlie the acquisition of an avoidance response. These results support a mechanism of active coping with conditioned fear that allows for the control over emotional responses such as fears that can become maladaptive and influence our decision-making.

  8. The neural correlates of negative prediction error signaling in human fear conditioning.

    Science.gov (United States)

    Spoormaker, V I; Andrade, K C; Schröter, M S; Sturm, A; Goya-Maldonado, R; Sämann, P G; Czisch, M

    2011-02-01

    In a temporal difference (TD) learning approach to classical conditioning, a prediction error (PE) signal shifts from outcome deliverance to the onset of the conditioned stimulus. Omission of an expected outcome results in a negative PE signal, which is the initial step towards successful extinction. In order to visualize negative PE signaling during fear conditioning, we employed combined functional magnetic resonance (fMRI) and skin conductance response (SCR) measurements in a conditioning task with visual stimuli and mild electrical shocks. Positive PE signaling was associated with increased activation in the bilateral insula, supplementary motor area, brainstem, and visual cortices. Negative PE signaling was associated with increased activation in the ventromedial and dorsolateral prefrontal cortices, the left lateral orbital gyrus, the middle temporal gyri, angular gyri, and visual cortices. The involvement of the ventromedial prefrontal and orbitofrontal cortex in extinction learning has been well documented, and this study provides evidence for the notion that these regions are already involved in negative PE signaling during fear conditioning. PMID:20869454

  9. The effects of transcutaneous vagus nerve stimulation on conditioned fear extinction in humans.

    Science.gov (United States)

    Burger, Andreas M; Verkuil, Bart; Van Diest, Ilse; Van der Does, Willem; Thayer, Julian F; Brosschot, Jos F

    2016-07-01

    A critical component of the treatment for anxiety disorders is the extinction of fear via repeated exposure to the feared stimulus. This process is strongly dependent on successful memory formation and consolidation. Stimulation of the vagus nerve enhances memory formation in both animals and humans. The objective of this study was to assess whether transcutaneous stimulation of the vagus nerve (tVNS) can accelerate extinction memory formation and retention in fear conditioned humans. To assess fear conditioning and subsequent fear extinction, we assessed US expectancy ratings, fear potentiated startle responses and phasic heart rate responses. We conducted a randomized controlled trial in thirty-one healthy participants. After fear conditioning participants were randomly assigned to receive tVNS or sham stimulation during the extinction phase. Retention of extinction memory was tested 24h later. tVNS accelerated explicit fear extinction learning (US expectancy ratings), but did not lead to better retention of extinction memory 24h later. We did not find a differential physiological conditioning response during the acquisition of fear and thus were unable to assess potential effects of tVNS on the extinction of physiological indices of fear. These findings complement recent studies that suggest vagus nerve stimulation could be a promising tool to improve memory consolidation and fear extinction. PMID:27222436

  10. Neuropeptide S reduces fear and avoidance of con-specifics induced by social fear conditioning and social defeat, respectively.

    Science.gov (United States)

    Zoicas, Iulia; Menon, Rohit; Neumann, Inga D

    2016-09-01

    Neuropeptide S (NPS) has anxiolytic effects and facilitates extinction of cued fear in rodents. Here, we investigated whether NPS reverses social fear and social avoidance induced by social fear conditioning (SFC) and acute social defeat (SD), respectively, in male CD1 mice. Our results revealed that intracerebroventricular NPS (icv; 10 and 50 nmol/2 μl) reversed fear of unknown con-specifics induced by SFC and dose-dependently reduced avoidance of known aggressive con-specifics induced by SD. While 50 nmol of NPS completely reversed social avoidance and reinstated social preference, 10 nmol of NPS reduced social avoidance, but did not completely reinstate social preference in socially-defeated mice. Further, a lower dose (1 nmol/2 μl) of NPS facilitated the within-session extinction of cued fear, while a higher dose (10 nmol/2 μl) reduced the expression of cued fear. We could also confirm the anxiolytic effects of NPS (1, 10 and 50 nmol/2 μl) on the elevated plus-maze (EPM), which were not accompanied by alterations in locomotor activity either on the EPM or in the home cage. Finally, we could show that icv infusion of the NPS receptor 1 antagonist D-Cys((t)Bu)(5)-NPS (10 nmol/2 μl) did not alter SFC-induced social fear, general anxiety and locomotor activity. Taken together, our study extends the potent anxiolytic profile of NPS to a social context by demonstrating the reduction of social fear and social avoidance, thus providing the framework for studies investigating the involvement of the NPS system in the regulation of different types of social behaviour. PMID:27044664

  11. Influence of context and contingency awareness on fear conditioning – an investigation in virtual reality

    OpenAIRE

    Ewald, Heike

    2015-01-01

    Fear conditioning is an efficient model of associative learning, which has greatly improved our knowledge of processes underlying the development and maintenance of pathological fear and anxiety. In a differential fear conditioning paradigm, one initially neutral stimulus (NS) is paired with an aversive event (unconditioned stimulus, US), whereas another stimulus does not have any consequences. After a few pairings the NS is associated with the US and consequently becomes a conditioned stimul...

  12. Fear conditioning and extinction across development: evidence from human studies and animal models.

    Science.gov (United States)

    Shechner, Tomer; Hong, Melanie; Britton, Jennifer C; Pine, Daniel S; Fox, Nathan A

    2014-07-01

    The ability to differentiate danger and safety through associative processes emerges early in life. Understanding the mechanisms underlying associative learning of threat and safety can clarify the processes that shape development of normative fears and pathological anxiety. Considerable research has used fear conditioning and extinction paradigms to delineate underlying mechanisms in animals and human adults; however, little is known about these mechanisms in children and adolescents. The current paper summarizes the empirical data on the development of fear conditioning and extinction. It reviews methodological considerations and future directions for research on fear conditioning and extinction in pediatric populations. PMID:24746848

  13. Adversity-induced relapse of fear: neural mechanisms and implications for relapse prevention from a study on experimentally induced return-of-fear following fear conditioning and extinction.

    Science.gov (United States)

    Scharfenort, R; Menz, M; Lonsdorf, T B

    2016-01-01

    The efficacy of current treatments for anxiety disorders is limited by high relapse rates. Relapse of anxiety disorders and addiction can be triggered by exposure to life adversity, but the underlying mechanisms remain unexplored. Seventy-six healthy adults were a priori selected for the presence or absence of adverse experiences during childhood (CA) and recent past (RA; that is, past 12 months). Participants underwent fear conditioning (day 1) and fear extinction and experimental return-of-fear (ROF) induction through reinstatement (a model for adversity-induced relapse; day 2). Ratings, autonomic (skin conductance response) and neuronal activation measures (functional magnetic resonance imaging (fMRI)) were acquired. Individuals exposed to RA showed a generalized (that is, not CS- specific) fear recall and ROF, whereas unexposed individuals showed differential (that is, CS+ specific) fear recall and ROF on an autonomic level despite no group differences during fear acquisition and extinction learning. These group differences in ROF were accompanied by corresponding activation differences in brain areas known to be involved in fear processing and differentiability/generalization of ROF (that is, hippocampus). In addition, dimensional measures of RA, CA and lifetime adversity were negatively correlated with differential skin conductance responses (SCRs) during ROF and hippocampal activation. As discriminating signals of danger and safety, as well as a tendency for overgeneralization, are core features in clinically anxious populations, these deficits may specifically contribute to relapse risk following exposure to adversity, in particular to recent adversity. Hence, our results may provide first and novel insights into the possible mechanisms mediating enhanced relapse risk following exposure to (recent) adversity, which may guide the development of effective pre- and intervention programs. PMID:27434492

  14. Conditioned Fear Associated Phenotypes as Robust, Translational Indices of Trauma-, Stressor-, and Anxiety-related Behaviors

    Directory of Open Access Journals (Sweden)

    Maria Anne Briscione

    2014-07-01

    Full Text Available Posttraumatic stress disorder (PTSD is a heterogeneous disorder that affects individuals exposed to trauma (e.g., combat, interpersonal violence, and natural disasters. It is characterized by hyperarousal, intrusive reminders of the trauma, avoidance of trauma-related cues, and negative cognition and mood. This heterogeneity indicates the presence of multiple neurobiological mechanisms underlying the development and maintenance of PTSD. Fear conditioning is a robust, translational experimental paradigm that can be employed to elucidate these mechanisms by allowing for the study of fear-related dimensions of PTSD (e.g., fear extinction, fear inhibition, and generalization of fear across multiple units of analysis. Fear conditioning experiments have identified varying trajectories of the dimensions described, highlighting exciting new avenues of targeted, focused study. Additionally, fear conditioning studies provide a translational platform to develop novel interventions. The current review highlights the versatility of fear conditioning paradigms, the implications for pharmacological and non-pharmacological treatments, the robustness of these paradigms to span an array of neuroscientific measures (e.g., genetic studies, and finally the need to understand the boundary conditions under which these paradigms are effective. Further understanding these paradigms will ultimately allow for optimization of fear conditioning paradigms, a necessary step towards the advancement of PTSD treatment methods.

  15. Altered resting-state brain activity at functional MRI during automatic memory consolidation of fear conditioning.

    Science.gov (United States)

    Feng, Tingyong; Feng, Pan; Chen, Zhencai

    2013-07-26

    Investigations of fear conditioning in rodents and humans have illuminated the neural mechanisms of fear acquisition and extinction. However, the neural mechanism of automatic memory consolidation of fear conditioning is still unclear. To address this question, we measured brain activity following fear acquisition using resting-state functional magnetic resonance imaging (rs-fMRI). In the current study, we used a marker of fMRI, amplitude of low-frequency (0.01-0.08Hz) fluctuation (ALFF) to quantify the spontaneous brain activity. Brain activity correlated to fear memory consolidation was observed in parahippocampus, insula, and thalamus in resting-state. Furthermore, after acquired fear conditioning, compared with control group some brain areas showed ALFF increased in ventromedial prefrontal cortex (vmPFC) and anterior cingulate cortex (ACC) in the experimental group, whereas some brain areas showed decreased ALFF in striatal regions (caudate, putamen). Moreover, the change of ALFF in vmPFC was positively correlated with the subjective fear ratings. These findings suggest that the parahippocampus, insula, and thalamus are the neural substrates of fear memory consolidation. The difference in activity could be attributed to a homeostatic process in which the vmPFC and ACC were involved in the fear recovery process, and change of ALFF in vmPFC predicts subjective fear ratings. PMID:23726994

  16. Revealing context-specific conditioned fear memories with full immersion virtual reality

    Directory of Open Access Journals (Sweden)

    Nicole eHuff

    2011-11-01

    Full Text Available The extinction of conditioned fear is known to be context specific, and often referred to as more robustly contextually bound than the fear memory itself (Bouton, 2004. Yet, recent findings in rodents have challenged the notion that contextual fear retention is initially generalized. The context specificity of a cued-fear memory to the learning context has not been addressed in the human literature largely due to limitations in methodology. Here we adapt a novel technology to test the context specificity of cued fear conditioning using full immersion 3-dimensional virtual reality (VR. During acquisition training, healthy participants navigated through virtual environments containing dynamic snake and spider conditioned stimuli (CSs, one of which was paired with electrical wrist stimulation. During a 24-hour delayed retention test, one group returned to the same context as acquisition training whereas another group experienced the CSs in a novel context. Unconditioned stimulus (US expectancy ratings were assayed on-line during fear acquisition as an index of contingency awareness. Skin conductance responses (SCR time-locked to CS onset were the dependent measure of cued fear, and skin conductance levels during the interstimulus interval were an index of context fear. Findings indicate that early in acquisition training, participants express contingency awareness as well as differential contextual fear, whereas differential cued fear emerged later in acquisition. During the retention test, differential cued fear retention was enhanced in the group who returned to the same context as acquisition training relative to the context shift group. The results extend recent rodent work to illustrate differences in cued and context fear acquisition and the contextual specificity of recent fear memories. Findings support the use of full immersion VR as a novel tool in cognitive neuroscience to bridge rodent models of contextual phenomena underlying human

  17. Antagonism of Lateral Amygdala Alpha1-Adrenergic Receptors Facilitates Fear Conditioning and Long-Term Potentiation

    Science.gov (United States)

    Lazzaro, Stephanie C.; Hou, Mian; Cunha, Catarina; LeDoux, Joseph E.; Cain, Christopher K.

    2010-01-01

    Norepinephrine receptors have been studied in emotion, memory, and attention. However, the role of alpha1-adrenergic receptors in fear conditioning, a major model of emotional learning, is poorly understood. We examined the effect of terazosin, an alpha1-adrenergic receptor antagonist, on cued fear conditioning. Systemic or intra-lateral amygdala…

  18. A Discrete Population of Neurons in the Lateral Amygdala Is Specifically Activated by Contextual Fear Conditioning

    Science.gov (United States)

    Wilson, Yvette M.; Murphy, Mark

    2009-01-01

    There is no clear identification of the neurons involved in fear conditioning in the amygdala. To search for these neurons, we have used a genetic approach, the "fos-tau-lacZ" (FTL) mouse, to map functionally activated expression in neurons following contextual fear conditioning. We have identified a discrete population of neurons in the lateral…

  19. The Amygdala Is Critical for Trace, Delay, and Contextual Fear Conditioning

    Science.gov (United States)

    Kochli, Daniel E.; Thompson, Elaine C.; Fricke, Elizabeth A.; Postle, Abagail F.; Quinn, Jennifer J.

    2015-01-01

    Numerous investigations have definitively shown amygdalar involvement in delay and contextual fear conditioning. However, much less is known about amygdala contributions to trace fear conditioning, and what little evidence exists is conflicting as noted in previous studies. This discrepancy may result from selective targeting of individual nuclei…

  20. Dissociated Roles for the Lateral and Medial Septum in Elemental and Contextual Fear Conditioning

    Science.gov (United States)

    Calandreau, Ludovic; Jaffard, Robert; Desmedt, Aline

    2007-01-01

    Extensive evidence indicates that the septum plays a predominant role in fear learning, yet the direction of this control is still a matter of debate. Increasing data suggest that the medial (MS) and lateral septum (LS) would be differentially required in fear conditioning depending on whether a discrete conditional stimulus (CS) predicts, or not,…

  1. Updating versus Exposure to Prevent Consolidation of Conditioned Fear

    OpenAIRE

    Victoria Pile; Thorsten Barnhofer; Jennifer Wild

    2015-01-01

    Targeting the consolidation of fear memories following trauma may offer a promising method for preventing the development of flashbacks and other unwanted re-experiencing symptoms that characterise Posttraumatic Stress Disorder (PTSD). Research has demonstrated that performing visuo-spatial tasks after analogue trauma can block the consolidation of fear memory and reduce the frequency of flashbacks. However, no research has yet used verbal techniques to alter memories during the consolidation...

  2. Brain Oxytocin in Social Fear Conditioning and Its Extinction: Involvement of the Lateral Septum

    OpenAIRE

    Zoicas, Iulia; Slattery, David A.; Neumann, Inga D.

    2014-01-01

    Central oxytocin (OXT) has anxiolytic and pro-social properties both in humans and rodents, and has been proposed as a therapeutic option for anxiety and social dysfunctions. Here, we utilized a mouse model of social fear conditioning (SFC) to study the effects of OXT on social fear, and to determine whether SFC causes alterations in central OXT receptor (OXTR) binding and local OXT release. Central infusion of OXT, but not arginine vasopressin, prior to social fear extinction training comple...

  3. The Development of Skin Conductance Fear Conditioning in Children from Ages 3 to 8 Years

    OpenAIRE

    Gao, Yu; Raine, Adrian; Venables, Peter H.; Dawson, Michael E.; Mednick, Sarnoff A.

    2010-01-01

    Although fear conditioning is an important psychological construct implicated in behavioral and emotional problems little is known about how it develops in early childhood. Using a differential, partial reinforcement conditioning paradigm, this longitudinal study assessed skin conductance conditioned responses in 200 children at ages 3, 4, 5, 6, and 8 years. Results demonstrated that in both boys and girls: (1) fear conditioning increased across age, particularly from ages 5 to 6 years, (2) t...

  4. The role of the medial prefrontal cortex in the conditioning and extinction of fear

    Directory of Open Access Journals (Sweden)

    Thomas Francis Giustino

    2015-11-01

    Full Text Available Once acquired, a fearful memory can persist for a lifetime. Although learned fear can be extinguished, extinction memories are fragile. The resilience of fear memories to extinction may contribute to the maintenance of disorders of fear and anxiety, including post-traumatic stress disorder (PTSD. As such, considerable effort has been placed on understanding the neural circuitry underlying the acquisition, expression, and extinction of emotional memories in rodent models as well as in humans. A triad of brain regions, including the prefrontal cortex, hippocampus, and amygdala, form an essential brain circuit involved in fear conditioning and extinction. Within this circuit, the prefrontal cortex is thought to exert top-down control over subcortical structures to regulate appropriate behavioral responses. Importantly, a division of labor has been proposed in which the prelimbic (PL and infralimbic (IL subdivisions of the medial prefrontal cortex (mPFC regulate the expression and suppression of fear in rodents, respectively. Here we critically review the anatomical and physiological evidence that has led to this proposed dichotomy of function within mPFC. We propose that under some conditions, the PL and IL act in concert, exhibiting similar patterns of neural activity in response to aversive conditioned stimuli and during the expression or inhibition of conditioned fear. This may stem from common synaptic inputs, parallel downstream outputs, or cortico-cortical interactions. Despite this functional covariation, these mPFC subdivisions may still be coding for largely opposing behavioral outcomes, with PL biased towards fear expression and IL towards suppression.

  5. Functional imaging of stimulus convergence in amygdalar neurons during Pavlovian fear conditioning.

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    Sabiha K Barot

    Full Text Available BACKGROUND: Associative conditioning is a ubiquitous form of learning throughout the animal kingdom and fear conditioning is one of the most widely researched models for studying its neurobiological basis. Fear conditioning is also considered a model system for understanding phobias and anxiety disorders. A fundamental issue in fear conditioning regards the existence and location of neurons in the brain that receive convergent information about the conditioned stimulus (CS and unconditioned stimulus (US during the acquisition of conditioned fear memory. Convergent activation of neurons is generally viewed as a key event for fear learning, yet there has been almost no direct evidence of this critical event in the mammalian brain. METHODOLOGY/PRINCIPAL FINDINGS: Here, we used Arc cellular compartmental analysis of temporal gene transcription by fluorescence in situ hybridization (catFISH to identify neurons activated during single trial contextual fear conditioning in rats. To conform to temporal requirements of catFISH analysis we used a novel delayed contextual fear conditioning protocol which yields significant single- trial fear conditioning with temporal parameters amenable to catFISH analysis. Analysis yielded clear evidence that a population of BLA neurons receives convergent CS and US information at the time of the learning, that this only occurs when the CS-US arrangement is supportive of the learning, and that this process requires N-methyl-D-aspartate receptor activation. In contrast, CS-US convergence was not observed in dorsal hippocampus. CONCLUSIONS/SIGNIFICANCE: Based on the pattern of Arc activation seen in conditioning and control groups, we propose that a key requirement for CS-US convergence onto BLA neurons is the potentiation of US responding by prior exposure to a novel CS. Our results also support the view that contextual fear memories are encoded in the amygdala and that the role of dorsal hippocampus is to process and

  6. Different brain networks underlying the acquisition and expression of contextual fear conditioning: a metabolic mapping study.

    Science.gov (United States)

    González-Pardo, H; Conejo, N M; Lana, G; Arias, J L

    2012-01-27

    The specific brain regions and circuits involved in the acquisition and expression of contextual fear conditioning are still a matter of debate. To address this issue, regional changes in brain metabolic capacity were mapped during the acquisition and expression of contextual fear conditioning using cytochrome oxidase (CO) quantitative histochemistry. In comparison with a group briefly exposed to a conditioning chamber, rats that received a series of randomly presented footshocks in the same conditioning chamber (fear acquisition group) showed increased CO activity in anxiety-related brain regions like the ventral periaqueductal gray, the ventral hippocampus, the lateral habenula, the mammillary bodies, and the laterodorsal thalamic nucleus. Another group received randomly presented footshocks, and it was re-exposed to the same conditioning chamber one week later (fear expression group). The conditioned group had significantly higher CO activity as compared with the matched control group in the following brain regions: the ventral periaqueductal gray, the central and lateral nuclei of the amygdala, and the bed nucleus of the stria terminalis. In addition, analysis of functional brain networks using interregional CO activity correlations revealed different patterns of functional connectivity between fear acquisition and fear expression groups. In particular, a network comprising the ventral hippocampus and amygdala nuclei was found in the fear acquisition group, whereas a closed reciprocal dorsal hippocampal network was detected in the fear expression group. These results suggest that contextual fear acquisition and expression differ as regards to the brain networks involved, although they share common brain regions involved in fear, anxiety, and defensive behavior. PMID:22173014

  7. Fear conditioning fragments REM sleep in stress-sensitive Wistar-Kyoto, but not Wistar, rats

    OpenAIRE

    DaSilva, Jamie K.; Lei, Yanlin; Madan, Vibha; Mann, Graziella L.; Richard J. Ross; Tejani-Butt, Shanaz; Morrison, Adrian R.

    2010-01-01

    Pavlovian conditioning is commonly used to investigate the mechanisms of fear learning. Because the Wistar-Kyoto (WKY) rat strain is particularly stress-sensitive, we investigated the effects of a psychological stressor on sleep in WKY compared to Wistar (WIS) rats. Male WKY and WIS rats were either fear-conditioned to tone cues or received electric foot shocks alone. In the fear-conditioning procedure, animals were exposed to 10 tones (800 Hz, 90 dB, 5 sec), each co-terminating with a foot s...

  8. Human Fear Conditioning Conducted in Full Immersion 3-Dimensional Virtual Reality

    OpenAIRE

    Huff, Nicole C.; Zielinski, David J.; Fecteau, Matthew E.; Brady, Rachael; LaBar, Kevin S.

    2010-01-01

    Fear conditioning is a widely used paradigm in non-human animal research to investigate the neural mechanisms underlying fear and anxiety. A major challenge in conducting conditioning studies in humans is the ability to strongly manipulate or simulate the environmental contexts that are associated with conditioned emotional behaviors. In this regard, virtual reality (VR) technology is a promising tool. Yet, adapting this technology to meet experimental constraints requires special accommodati...

  9. Generalization of Conditioned Fear-Potentiated Startle in Humans: Experimental Validation and Clinical Relevance

    OpenAIRE

    Lissek, Shmuel; Biggs, Arter L.; Rabin, Stephanie J.; Cornwell, Brian R.; Ruben P Alvarez; Pine, Daniel S.; Grillon, Christian

    2008-01-01

    Though generalization of conditioned fear has been implicated as a central feature of pathological anxiety, surprisingly little is known about the psychobiology of this learning phenomenon in humans. Whereas animal work has frequently applied methods to examine generalization gradients to study the gradual weakening of the conditioned-fear response as the test stimulus increasingly differs from the conditioned stimulus (CS), to our knowledge no psychobiological studies of such gradients have ...

  10. Hippocampal NMDA receptors are necessary for auditory trace fear conditioning measured with conditioned hypoalgesia in rats.

    Science.gov (United States)

    Seo, Dong-Oh; Pang, Min-Hee; Shin, Maeng-Sik; Kim, Hyun-Taek; Choi, June-Seek

    2008-10-10

    We tested whether N-methyl-D-aspartate (NMDA) receptors in the dorsal hippocampus (DH) are critical for the acquisition of trace fear conditioning using conditioned hypoalgesia (CHA), decrease in pain reactivity, as the conditioned response (CR) instead of commonly used freezing. Infusions of the NMDA receptor antagonist, DL-2-amino-5-phosphonovaleric acid (APV) into DH prior to conditioning resulted in impaired CHA, measured with the radiant heat tail flick test, only in the trace-conditioning group when they were tested during the trace interval. The same infusion had no effect on CHA in the delay-conditioned animals. The results support that NMDA receptors in DH are critically involved in associating the CS with the US across a temporal gap. In addition, temporal specificity of the CR was revealed as CHA was induced only in the temporal vicinity of the US used for the training. PMID:18514922

  11. Reconsolidation in a human fear conditioning study: a test of extinction as updating mechanism.

    Science.gov (United States)

    Kindt, Merel; Soeter, Marieke

    2013-01-01

    Disrupting reconsolidation seems to be a promising approach to dampen the expression of fear memory. Recently, we demonstrated that disrupting reconsolidation by a pharmacological manipulation specifically targeted the emotional expression of memory (i.e., startle response). Here we test in a human differential fear-conditioning paradigm with fear-relevant stimuli whether the spacing of a single unreinforced retrieval trial relative to extinction learning allows for "rewriting" the original fear association, thereby preventing the return of fear. In contrast to previous findings reported by Schiller et al. (2010), who used a single-method for indexing fear (skin conductance response) and fear-irrelevant stimuli, we found that extinction learning within the reconsolidation window did not prevent the recovery of fear on multiple indices of conditioned responding (startle response, skin conductance response and US-expectancy). These conflicting results ask for further critical testing given the potential impact on the field of emotional memory and its application to clinical practice. PMID:21986472

  12. Memory consolidation of fear conditioning: bi-stable amygdala connectivity with dorsal anterior cingulate and medial prefrontal cortex.

    Science.gov (United States)

    Feng, Pan; Feng, Tingyong; Chen, Zhencai; Lei, Xu

    2014-11-01

    Investigations of fear conditioning in rodents and humans have illuminated the neural mechanisms of fear acquisition and extinction. However, the neural mechanism of memory consolidation of fear conditioning is not well understood. To address this question, we measured brain activity and the changes in functional connectivity following fear acquisition using resting-state functional magnetic resonance imaging. The amygdala-dorsal anterior cingulate cortex (dACC) and hippocampus-insula functional connectivity were enhanced, whereas the amygdala-medial prefrontal cortex (mPFC) functional coupling was decreased during fear memory consolidation. Furthermore, the amygdala-mPFC functional connectivity was negatively correlated with the subjective fear ratings. These findings suggest the amygdala functional connectivity with dACC and mPFC may play an important role in memory consolidation of fear conditioning. The change of amygdala-mPFC functional connectivity could predict the subjective fear. Accordingly, this study provides a new perspective for understanding fear memory consolidation. PMID:24194579

  13. Maltreatment Exposure, Brain Structure, and Fear Conditioning in Children and Adolescents.

    Science.gov (United States)

    McLaughlin, Katie A; Sheridan, Margaret A; Gold, Andrea L; Duys, Andrea; Lambert, Hilary K; Peverill, Matthew; Heleniak, Charlotte; Shechner, Tomer; Wojcieszak, Zuzanna; Pine, Daniel S

    2016-07-01

    Alterations in learning processes and the neural circuitry that supports fear conditioning and extinction represent mechanisms through which trauma exposure might influence risk for psychopathology. Few studies examine how trauma or neural structure relates to fear conditioning in children. Children (n=94) aged 6-18 years, 40.4% (n=38) with exposure to maltreatment (physical abuse, sexual abuse, or domestic violence), completed a fear conditioning paradigm utilizing blue and yellow bells as conditioned stimuli (CS+/CS-) and an aversive alarm noise as the unconditioned stimulus. Skin conductance responses (SCR) and self-reported fear were acquired. Magnetic resonance imaging data were acquired from 60 children. Children without maltreatment exposure exhibited strong differential conditioning to the CS+ vs CS-, based on SCR and self-reported fear. In contrast, maltreated children exhibited blunted SCR to the CS+ and failed to exhibit differential SCR to the CS+ vs CS- during early conditioning. Amygdala and hippocampal volume were reduced among children with maltreatment exposure and were negatively associated with SCR to the CS+ during early conditioning in the total sample, although these associations were negative only among non-maltreated children and were positive among maltreated children. The association of maltreatment with externalizing psychopathology was mediated by this perturbed pattern of fear conditioning. Child maltreatment is associated with failure to discriminate between threat and safety cues during fear conditioning in children. Poor threat-safety discrimination might reflect either enhanced fear generalization or a deficit in associative learning, which may in turn represent a central mechanism underlying the development of maltreatment-related externalizing psychopathology in children. PMID:26677946

  14. Correlations between psychological tests and physiological responses during fear conditioning and renewal

    OpenAIRE

    Martínez Karen G; Castro-Couch Melissa; Franco-Chaves José A; Ojeda-Arce Brenda; Segura Gustavo; Milad Mohammed R; Quirk Gregory J

    2012-01-01

    Abstract Background Anxiety disorders are characterized by specific emotions, thoughts and physiological responses. Little is known, however, about the relationship between psychological/personality indices of anxiety responses to fear stimuli. Methods We studied this relationship in healthy subjects by comparing scores on psychological and personality questionnaires with results of an experimental fear conditioning paradigm using a visual conditioned stimulus (CS). We measured skin conductan...

  15. Differences in hippocampal CREB phosphorylation in trace fear conditioning of two inbred mouse strains

    OpenAIRE

    Hwang, Yoo Kyeong; Song, Jae-Chun; Han, Seol-Heui; Cho, Jeiwon; Smith, Dani R.; Gallagher, Michela; Han, Jung-Soo

    2010-01-01

    The effects of genetic background on fear trace conditioning were evaluated in relation to phosphorylated levels of cAMP response element-binding protein (CREB) in the hippocampus using two different inbred strains of mice, C57BL/6 and DBA/2. The male mice received a trace fear conditioning protocol and unpaired control groups were included to assess nonassociative effects on test performance. Both C57BL/6 and DBA/2 mice with paired training displayed higher freezing responses during testing ...

  16. Corticotropin releasing factor type-1 receptor antagonism in the dorsolateral bed nucleus of the stria terminalis disrupts contextually conditioned fear, but not unconditioned fear to a predator odor.

    Science.gov (United States)

    Asok, Arun; Schulkin, Jay; Rosen, Jeffrey B

    2016-08-01

    The bed nucleus of the stria terminalis (BNST) plays a critical role in fear and anxiety. The BNST is important for contextual fear learning, but the mechanisms regulating this function remain unclear. One candidate mechanism is corticotropin-releasing-factor (CRF) acting at CRF type 1 receptors (CRFr1s). Yet, there has been little progress in elucidating if CRFr1s in the BNST are involved in different types of fear (conditioned and/or unconditioned). Therefore, the present study investigated the effect of antalarmin, a potent CRFr1 receptor antagonist, injected intracerebroventricularly (ICV) and into the dorsolateral BNST (LBNST) during single trial contextual fear conditioning or exposure to the predator odor 2,5-dihydro-2,4,5-trimethylthiazoline (TMT). Neither ICV nor LBNST antalarmin disrupted unconditioned freezing to TMT. In contrast, ICV and LBNST antalarmin disrupted the retention of contextual fear when tested 24h later. Neither ICV nor LBNST antalarmin affected baseline or post-shock freezing-indicating antalarmin does not interfere with the early phases of contextual fear acquisition. Antalarmin did not (1) permanently affect the ability to learn and express contextual fear, (2) change responsivity to footshocks, or (3) affect the ability to freeze. Our findings highlight an important role for CRFr1s within the LBNST during contextually conditioned fear, but not unconditioned predator odor fear. PMID:27153520

  17. Influence of stress on fear memory processes in an aversive differential conditioning paradigm in humans.

    Science.gov (United States)

    Bentz, Dorothée; Michael, Tanja; Wilhelm, Frank H; Hartmann, Francina R; Kunz, Sabrina; von Rohr, Isabelle R Rudolf; de Quervain, Dominique J-F

    2013-07-01

    It is widely assumed that learning and memory processes play an important role in the pathogenesis, expression, maintenance and therapy of anxiety disorders, such as phobias or post-traumatic stress disorder (PTSD). Memory retrieval is involved in symptom expression and maintenance of these disorders, while memory extinction is believed to be the underlying mechanism of behavioral exposure therapy of anxiety disorders. There is abundant evidence that stress and stress hormones can reduce memory retrieval of emotional information, whereas they enhance memory consolidation of extinction training. In this study we aimed at investigating if stress affects these memory processes in a fear conditioning paradigm in healthy human subjects. On day 1, fear memory was acquired through a standard differential fear conditioning procedure. On day 2 (24h after fear acquisition), participants either underwent a stressful cold pressor test (CPT) or a control condition, 20 min before memory retrieval testing and extinction training. Possible prolonged effects of the stress manipulation were investigated on day 3 (48 h after fear acquisition), when memory retrieval and extinction were tested again. On day 2, men in the stress group showed a robust cortisol response to stress and showed lower unconditioned stimulus (US) expectancy ratings than men in the control group. This reduction in fear memory retrieval was maintained on day 3. In women, who showed a significantly smaller cortisol response to stress than men, no stress effects on fear memory retrieval were observed. No group differences were observed with respect to extinction. In conclusion, the present study provides evidence that stress can reduce memory retrieval of conditioned fear in men. Our findings may contribute to the understanding of the effects of stress and glucocorticoids on fear symptoms in anxiety disorders and suggest that such effects may be sex-specific. PMID:23333200

  18. The Role of Nucleus Accumbens Shell in Learning about Neutral versus Excitatory Stimuli during Pavlovian Fear Conditioning

    Science.gov (United States)

    Bradfield, Laura A.; McNally, Gavan P.

    2010-01-01

    We studied the role of nucleus accumbens shell (AcbSh) in Pavlovian fear conditioning. Rats were trained to fear conditioned stimulus A (CSA) in Stage I, which was then presented in compound with a neutral stimulus and paired with shock in Stage II. AcbSh lesions had no effect on fear-learning to CSA in Stage I, but selectively prevented learning…

  19. The usefulness of olfactory fear conditioning for the study of early emotional and cognitive impairment in reserpine model.

    Science.gov (United States)

    Souza, Rimenez R; França, Sanmara L; Bessa, Marília M; Takahashi, Reinaldo N

    2013-11-01

    Due to the ability for depleting neuronal storages of monoamines, the reserpine model is a suitable approach for the investigation of the neurobiology of neurodegenerative diseases. However, the behavioral effects of low doses of reserpine are not always detected by classic animal tests of cognition, emotion, and sensory ability. In this study, the effects of reserpine (0.5-1.0mg/kg) were evaluated in olfactory fear conditioning, inhibitory avoidance, open-field, elevated plus-maze, and olfactory discrimination. Possible protective effects were also investigated. We found that single administration of reserpine impaired the acquisition of olfactory fear conditioning (in both doses) as well as olfactory discrimination (in the higher dose), while no effects were seen in all other tests. Additionally, we demonstrated that prior exposure to environmental enrichment prevented effects of reserpine in animals tested in olfactory fear conditioning. Altogether, these findings suggest that a combined cognitive, emotional and sensory-dependent task would be more sensitive to the effects of the reserpine model. In addition, the present data support the environmental enrichment as an useful approach for the study of resilience mechanisms in neurodegenerative processes. PMID:23978602

  20. Individual differences in discriminatory fear learning under conditions of ambiguity: A vulnerability factor for anxiety disorders?

    Directory of Open Access Journals (Sweden)

    TomBeckers

    2013-05-01

    Full Text Available Complex fear learning procedures might be better suited than the common differential fear conditioning paradigm for detecting individual differences related to vulnerability for anxiety disorders. Two such procedures are the blocking procedure and the protection-from-overshadowing procedure. Their comparison allows for the examination of discriminatory fear learning under conditions of ambiguity. The present study examined the role of individual differences in such discriminatory fear learning. We hypothesized that heightened trait anxiety would be related to a deficit in discriminatory fear learning. Participants gave US-expectancy ratings as an index for the threat value of individual CSs following blocking and protection-from-overshadowing training. The difference in threat value at test between the protected-from-overshadowing CS and the blocked CS was negatively correlated with scores on a self-report tension-stress scale that approximates facets of generalized anxiety disorder (DASS-S, but not with other individual difference variables. In addition, a behavioral test showed that only participants scoring high on the DASS-S avoided the protected-from-overshadowing CS. This observed deficit in discriminatory fear learning for participants with high levels of tension-stress might be an underlying mechanism for fear overgeneralization in diffuse anxiety disorders such as generalized anxiety disorder.

  1. Correlations between psychological tests and physiological responses during fear conditioning and renewal

    Directory of Open Access Journals (Sweden)

    Martínez Karen G

    2012-09-01

    Full Text Available Abstract Background Anxiety disorders are characterized by specific emotions, thoughts and physiological responses. Little is known, however, about the relationship between psychological/personality indices of anxiety responses to fear stimuli. Methods We studied this relationship in healthy subjects by comparing scores on psychological and personality questionnaires with results of an experimental fear conditioning paradigm using a visual conditioned stimulus (CS. We measured skin conductance response (SCR during habituation, conditioning, and extinction; subsequently testing for recall and renewal of fear 24 hours later. Results We found that multiple regression models explained 45% of the variance during conditioning to the CS+, and 24% of the variance during renewal of fear to the CS+. Factors that explained conditioning included lower levels of conscientiousness, increased baseline reactivity (SCL, and response to the shock (UCR. Low levels of extraversion correlated with greater renewal. No model could be found to explain extinction learning or extinction recall to the CS+. Conclusions The lack of correlation of fear extinction with personality and neuropsychological indices suggests that extinction may be less determined by trait variables and cognitive state, and may depend more on the subject’s current emotional state. The negative correlation between fear renewal and extraversion suggests that this personality characteristic may protect against post-treatment relapse of symptoms of anxiety disorders.

  2. Classical conditioning in patients with severe memory problems.

    OpenAIRE

    Daum, I; Channon, S; Canavan, A G

    1989-01-01

    Classical conditioning is one of the most fundamental forms of learning, and yet little is known regarding the effects of brain injury on conditioning processes in humans. Three patients with temporal lobe lesions and severe memory problems were therefore assessed in terms of eyeblink conditioning, extinction, discrimination and reversal learning, and in one patient electrodermal conditioning was also investigated. The acquisition of conditioned responses was seen to be intact, but the eviden...

  3. Contextual fear induced by unpredictability in a human fear conditioning preparation is related to the chronic expectation of a threatening US

    NARCIS (Netherlands)

    D. Vansteenwegen; C. Iberico; B. Vervliet; D. Hermans

    2008-01-01

    The present study was set up to investigate cued and contextual fear in situations of (un)predictability in a human fear conditioning paradigm. Forty-nine participants were presented with two different contexts (switching on and off the central lighting of the experimental room). In the predictable

  4. Fear conditioning and extinction across development: Evidence from human studies and animal models☆

    OpenAIRE

    Shechner, Tomer; Hong, Melanie; Britton, Jennifer C.; Pine, Daniel S.; Fox, Nathan A.

    2014-01-01

    The ability to differentiate danger and safety through associative processes emerges early in life. Understanding the mechanisms underlying associative learning of threat and safety can clarify the processes that shape development of normative fears and pathological anxiety. Considerable research has used fear conditioning and extinction paradigms to delineate underlying mechanisms in animals and human adults; however, little is known about these mechanisms in children and adolescents. The cu...

  5. Prereactivation propranolol fails to reduce skin conductance reactivity to prepared fear-conditioned stimuli.

    Science.gov (United States)

    Spring, Justin D; Wood, Nellie E; Mueller-Pfeiffer, Christoph; Milad, Mohammed R; Pitman, Roger K; Orr, Scott P

    2015-03-01

    Pharmacologic blockade of memory reconsolidation has been demonstrated in fear-conditioned rodents and humans and may provide a means to reduce fearfulness in anxiety disorders and posttraumatic stress disorder. Studying the efficacy of potential interventions in clinical populations is challenging, creating a need for paradigms within which candidate reconsolidation-blocking interventions can be readily tested. We used videos of biologically prepared conditioned stimuli (tarantulas) to test the efficacy of propranolol in blocking reconsolidation of conditioned fear in healthy young adults. Strong differential conditioning, measured by skin conductance, was observed among a screened subset of participants during acquisition. However, subsequent propranolol failed to reduce reactivity to the reactivated conditioned stimulus. These results are consistent with other recent findings and point to a need for testing other candidate drugs. PMID:25224026

  6. Delayed extinction fails to reduce skin conductance reactivity to fear-conditioned stimuli.

    Science.gov (United States)

    Fricchione, Jon; Greenberg, Mark S; Spring, Justin; Wood, Nellie; Mueller-Pfeiffer, Christoph; Milad, Mohammed R; Pitman, Roger K; Orr, Scott P

    2016-09-01

    A brief 10-min time delay between an initial and subsequent exposure to extinction trials has been found to impair memory reconsolidation in fear-conditioned rodents and humans, providing a potential means to reduce fearfulness in anxiety disorders and posttraumatic stress disorder (PTSD). The present study used videos of biologically prepared, conditioned stimuli (tarantulas) to test the efficacy of delayed extinction in blocking reconsolidation of conditioned fear in healthy young adults. Strong differential conditioning, measured by skin conductance, was observed among a screened subset of participants during acquisition. However, the delayed-extinction intervention failed to reduce reactivity to the conditioned stimulus paired with the extinction delay. These results are partially consistent with other recent, mixed findings and point to a need for testing other candidate interventions designed to interfere with the reconsolidation process. PMID:27314560

  7. The Development of Skin Conductance Fear Conditioning in Children from Ages 3 to 8 Years

    Science.gov (United States)

    Gao, Yu; Raine, Adrian; Venables, Peter H.; Dawson, Michael E.; Mednick, Sarnoff A.

    2010-01-01

    Although fear conditioning is an important psychological construct implicated in behavioral and emotional problems, little is known about how it develops in early childhood. Using a differential, partial reinforcement conditioning paradigm, this longitudinal study assessed skin conductance conditioned responses in 200 children at ages 3, 4, 5, 6,…

  8. Generalization of Pain-Related Fear Using a Left-Right Hand Judgment Conditioning Task.

    Science.gov (United States)

    Meulders, Ann; Harvie, Daniel S; Lorimer Moseley, G; Vlaeyen, Johan W S

    2015-09-01

    Recent research suggests that the mere intention to perform a painful movement can elicit pain-related fear. Based on these findings, the present study aimed to determine whether imagining a movement that is associated with pain (CS+) can start to elicit conditioned pain-related fear as well and whether pain-related fear elicited by imagining a painful movement can spread towards novel, similar but distinct imagined movements. We proposed a new experimental paradigm that integrates the left-right hand judgment task (HJT) with a differential fear conditioning procedure. During Acquisition, one hand posture (CS+) was consistently followed by a painful electrocutaneous stimulus (pain-US) and another hand posture (CS-) was not. Participants were instructed to make left-right judgments, which involve mentally rotating their own hand to match the displayed hand postures (i.e., motor imagery). During Generalization, participants were presented with a series of novel hand postures with six grades of perceptual similarity to the CS+ (generalization stimuli; GSs). Finally, during Extinction, the CS+ hand posture was no longer reinforced. The results showed that (1) a painful hand posture triggers fear and increased US-expectancy as compared to a nonpainful hand posture, (2) this pain-related fear spreads to similar but distinct hand postures following a generalization gradient, and subsequently, (3) it can be successfully reduced during extinction. These effects were apparent in the verbal ratings, but not in the startle measures. Because of the lack of effect in the startle measures, we cannot draw firm conclusions about whether the "imagined movements" (i.e., motor imagery of the hand postures) gained associative strength rather than the hand posture pictures itself. From a clinical perspective, basic research into generalization of pain-related fear triggered by covert CSs such as intentions, imagined movements and movement-related cognitions might further our

  9. Inhibition of the amygdala central nucleus by stimulation of cerebellar output in rats: a putative mechanism for extinction of the conditioned fear response.

    Science.gov (United States)

    Magal, Ari; Mintz, Matti

    2014-11-01

    The amygdala and the cerebellum serve two distinctively different functions. The amygdala plays a role in the expression of emotional information, whereas the cerebellum is involved in the timing of discrete motor responses. Interaction between these two systems is the basis of the two-stage theory of learning, according to which an encounter with a challenging event triggers fast classical conditioning of fear-conditioned responses in the amygdala and slow conditioning of motor-conditioned responses in the cerebellum. A third stage was hypothesised when an apparent interaction between amygdala and cerebellar associative plasticity was observed: an adaptive rate of cerebellum-dependent motor-conditioned responses was associated with a decrease in amygdala-dependent fear-conditioned responses, and was interpreted as extinction of amygdala-related fear-conditioned responses by the cerebellar output. To explore this hypothesis, we mimicked some components of classical eyeblink conditioning in anesthetised rats by applying an aversive periorbital pulse as an unconditioned stimulus and a train of pulses to the cerebellar output nuclei as a cerebellar neuronal-conditioned response. The central amygdala multiple unit response to the periorbital pulse was measured with or without a preceding train to the cerebellar output nuclei. The results showed that activation of the cerebellar output nuclei prior to periorbital stimulation produced diverse patterns of inhibition of the amygdala response to the periorbital aversive stimulus, depending upon the nucleus stimulated, the laterality of the nucleus stimulated, and the stimulus interval used. These results provide a putative extinction mechanism of learned fear behavior, and could have implications for the treatment of pathologies involving abnormal fear responses by using motor training as therapy. PMID:25185877

  10. Brain c-Fos immunocytochemistry and cytochrome oxidase histochemistry after a fear conditioning task.

    Science.gov (United States)

    Conejo, Nélida M; González Pardo, Héctor; López, Matías; Cantora, Raúl; Arias, Jorge L

    2007-05-01

    The involvement of the basolateral and the medial amygdala in fear conditioning was evaluated using different markers of neuronal activation. The method described here is a combination of cytochrome oxidase (CO) histochemistry and c-Fos immunocytochemistry on fresh frozen brain sections. Freezing behavior was used as an index of auditory and contextual fear conditioning. As expected, freezing scores were significantly higher in rats exposed to tone-shock pairings in a distinctive environment (conditioned; COND), as compared to rats that did not receive any shocks (UNCD). CO labeling was increased in the basolateral and medial amygdala of the COND group. Conversely, c-Fos expression in the basolateral and medial amygdala was lower in the COND group as compared to the UNCD group. Furthermore, c-Fos expression was particularly high in the medial amygdala of the UNCD group. The data provided by both techniques indicate that these amygdalar nuclei could play different roles on auditory and contextual fear conditioning. PMID:17425902

  11. Fear Conditioning in an Abdominal Pain Model: Neural Responses during Associative Learning and Extinction in Healthy Subjects

    OpenAIRE

    Kattoor, Joswin; Gizewski, Elke R.; Kotsis, Vassilios; Benson, Sven; Gramsch, Carolin; Theysohn, Nina; Maderwald, Stefan; Forsting, Michael; Schedlowski, Manfred; Elsenbruch, Sigrid

    2013-01-01

    Fear conditioning is relevant for elucidating the pathophysiology of anxiety, but may also be useful in the context of chronic pain syndromes which often overlap with anxiety. Thus far, no fear conditioning studies have employed aversive visceral stimuli from the lower gastrointestinal tract. Therefore, we implemented a fear conditioning paradigm to analyze the conditioned response to rectal pain stimuli using fMRI during associative learning, extinction and reinstatement. In N = 21 healthy h...

  12. Role of classical conditioning in learning gastrointestinal symptoms

    Institute of Scientific and Technical Information of China (English)

    Ursula Stockhorst; Paul Enck; Sibylle Klosterhalfen

    2007-01-01

    Nausea and/or vomiting are aversive gastrointestinal (GI) symptoms. Nausea and vomiting manifest unconditionally after a nauseogenic experience. However,there is correlative, quasiexperimental and experimental evidence that nausea and vomiting can also be learned via classical (Pavlovian) conditioning and might occur in anticipation of the nauseogenic event. Classical conditioning of nausea can develop with chemotherapy in cancer patients. Initially, nausea and vomiting occur during and after the administration of cytotoxic drugs (post-treatment nausea and vomiting) as unconditioned responses (UR). In addition, 20%-30% of cancer patients receiving chemotherapy report these side effects, despite antiemetic medication, when being re-exposed to the stimuli that usually signal the chemotherapy session and its drug infusion. These symptoms are called anticipatory nausea (AN) and/or anticipatory vomiting (ANV) and are explained by classical conditioning. Moreover,there is recent evidence for the assumption that postchemotherapy nausea is at least partly influenced by learning. After summarizing the relevant assumptions of the conditioning model, revealing that a context can become a conditioned stimulus (CS), the present paper summarizes data that nausea and/or vomiting is acquired by classical conditioning and, consequently,may be alleviated by conditioning techniques. Our own research has focussed on two aspects and is emphasized here. First, a conditioned nausea model was established in healthy humans using body rotation as the nauseainducing treatment. The validity of this motion-sickness model to examine conditioning mechanisms in the acquisition and alleviation of conditioned nausea and associated endocrine and immunological responses is summarized. Results from the rotation-induced motion sickness model showed that gender is an important moderator variable to be considered in further studies.This paper concludes with a review of the application of the demonstrated

  13. Stress-induced enhancement of fear conditioning and sensitization facilitates extinction-resistant and habituation-resistant fear behaviors in a novel animal model of posttraumatic stress disorder.

    Science.gov (United States)

    Corley, Michael J; Caruso, Michael J; Takahashi, Lorey K

    2012-01-18

    Posttraumatic stress disorder (PTSD) is characterized by stress-induced symptoms including exaggerated fear memories, hypervigilance and hyperarousal. However, we are unaware of an animal model that investigates these hallmarks of PTSD especially in relation to fear extinction and habituation. Therefore, to develop a valid animal model of PTSD, we exposed rats to different intensities of footshock stress to determine their effects on either auditory predator odor fear extinction or habituation of fear sensitization. In Experiment 1, rats were exposed to acute footshock stress (no shock control, 0.4 mA, or 0.8 mA) immediately prior to auditory fear conditioning training involving the pairing of auditory clicks with a cloth containing cat odor. When presented to the conditioned auditory clicks in the next 5 days of extinction testing conducted in a runway apparatus with a hide box, rats in the two shock groups engaged in higher levels of freezing and head out vigilance-like behavior from the hide box than the no shock control group. This increase in fear behavior during extinction testing was likely due to auditory activation of the conditioned fear state because Experiment 2 demonstrated that conditioned fear behavior was not broadly increased in the absence of the conditioned auditory stimulus. Experiment 3 was then conducted to determine whether acute exposure to stress induces a habituation resistant sensitized fear state. We found that rats exposed to 0.8 mA footshock stress and subsequently tested for 5 days in the runway hide box apparatus with presentations of nonassociative auditory clicks exhibited high initial levels of freezing, followed by head out behavior and culminating in the occurrence of locomotor hyperactivity. In addition, Experiment 4 indicated that without delivery of nonassociative auditory clicks, 0.8 mA footshock stressed rats did not exhibit robust increases in sensitized freezing and locomotor hyperactivity, albeit head out vigilance

  14. L-type Voltage-Gated Calcium Channels in Conditioned Fear: A Genetic and Pharmacological Analysis

    Science.gov (United States)

    McKinney, Brandon C.; Sze, Wilson; White, Jessica A.; Murphy, Geoffrey G.

    2008-01-01

    Using pharmacological approaches, others have suggested that L-type voltage-gated calcium channels (L-VGCCs) mediate both consolidation and extinction of conditioned fear. In the absence of L-VGCC isoform-specific antagonists, we have begun to investigate the subtype-specific role of LVGCCs in consolidation and extinction of conditioned fear…

  15. Extensive Extinction in Multiple Contexts Eliminates the Renewal of Conditioned Fear in Rats

    Science.gov (United States)

    Thomas, Brian L.; Vurbic, Drina; Novak, Cheryl

    2009-01-01

    Two studies examined whether nonreinforcement of a stimulus in multiple contexts, instead of a single context, would decrease renewal of conditioned fear in rats (as assessed by conditioned suppression of lever pressing). In Experiment 1, renewal was measured after 36 nonreinforced CS trials delivered during six extinction sessions in a single…

  16. Fear conditioning in mouse lines genetically selected for binge-like ethanol drinking.

    Science.gov (United States)

    Crabbe, John C; Schlumbohm, Jason P; Hack, Wyatt; Barkley-Levenson, Amanda M; Metten, Pamela; Lattal, K Matthew

    2016-05-01

    The comorbidity of substance- and alcohol-use disorders (AUD) with other psychiatric conditions, especially those related to stress such as post-traumatic stress disorder (PTSD), is well-established. Binge-like intoxication is thought to be a crucial stage in the development of the chronic relapsing nature of the addictions, and self-medication through binge-like drinking is commonly seen in PTSD patients. We have selectively bred two separate High Drinking in the Dark (HDID-1 and HDID-2) mouse lines to reach high blood ethanol concentrations (BECs) after a 4-h period of access to 20% ethanol starting shortly after the onset of circadian dark. As an initial step toward the eventual goal of employing binge-prone HDID mice to study PTSD-like behavior including alcohol binge drinking, we sought first to determine their ability to acquire conditioned fear. We asked whether these mice acquired, generalized, or extinguished conditioned freezing to a greater or lesser extent than unselected control HS/Npt mice. In two experiments, we trained groups of 16 adult male mice in a standard conditioned fear protocol. Mice were tested for context-elicited freezing, and then, in a novel context, for cue-induced freezing. After extinction tests, renewal of conditioned fear was tested in the original context. Mice of all three genotypes showed typical fear responding. Context paired with shock elicited freezing behavior in a control experiment, but cue unpaired with shock did not. These studies indicate that fear learning per se does not appear to be influenced by genes causing predisposition to binge drinking, suggesting distinct neural mechanisms. However, HDID mice are shown to be a suitable model for studying the role of conditioned fear specifically in binge-like drinking. PMID:27139234

  17. Long-term memory of visually cued fear conditioning: roles of the nNOS gene and CREB

    OpenAIRE

    Kelley, Jonathan B.; Anderson, Karen L.; Altmann, Stefanie L.; Itzhak, Yossef

    2010-01-01

    Nitric oxide (NO) produced by neuronal nitric oxide synthase (nNOS) has a role in late-phase long-term potentiation (LTP) and long-term memory (LTM) formation. Our recent studies implicated NO signaling in contextual and auditory cued fear conditioning. The present study investigated the role of NO signaling in visually cued fear conditioning. First, visually cued fear conditioning was investigated in wild-type (WT) and nNOS knockout (KO) mice. Second, the effects of pharmacological modulator...

  18. Delay Eyeblink Classical Conditioning is Impaired in Fragile X Syndrome

    OpenAIRE

    Tobia, Michael J.; Woodruff-Pak, Diana S.

    2009-01-01

    We examined 400 ms delay eyeblink classical conditioning in 20 participants with Fragile X syndrome ages 17-77 years, and 20 age-matched, healthy control participants. The Fragile X group demonstrated impaired learning and abnormal conditioned response timing. Adults with Fragile X (n=16) were also tested at two successive 12-month follow-up sessions to examine reacquisition and long-term retention. Participants in groups older and younger than 45 years demonstrated significant learning durin...

  19. Delay and trace fear conditioning in a complex virtual learning environment - neural substrates of extinction

    Directory of Open Access Journals (Sweden)

    Heike eEwald

    2014-05-01

    Full Text Available Extinction is an important mechanism to inhibit initially acquired fear responses. There is growing evidence that the ventromedial prefrontal cortex (vmPFC inhibits the amygdala and therefore plays an important role in the extinction of delay fear conditioning. To our knowledge, there is no evidence on the role of the prefrontal cortex in the extinction of trace conditioning up to now. Thus, we compared brain structures involved in the extinction of human delay and trace fear conditioning in a between-subjects-design in an fMRI study. Participants were passively guided through a virtual environment during learning and extinction of conditioned fear. Two different lights served as conditioned stimuli (CS; as unconditioned stimulus (US a mildly painful electric stimulus was delivered. In the delay conditioning group (DCG the US was administered with offset of one light (CS+, whereas in the trace conditioning group (TCG the US was presented 4s after CS+ offset. Both groups showed insular and striatal activation during early extinction, but differed in their prefrontal activation. The vmPFC was mainly activated in the DCG, whereas the TCG showed activation of the dorsolateral prefrontal cortex (dlPFC during extinction. These results point to different extinction processes in delay and trace conditioning. VmPFC activation during extinction of delay conditioning might reflect the inhibition of the fear response. In contrast, dlPFC activation during extinction of trace conditioning may reflect modulation of working memory processes which are involved in bridging the trace interval and hold information in short term memory.

  20. Delay and trace fear conditioning in a complex virtual learning environment-neural substrates of extinction.

    Science.gov (United States)

    Ewald, Heike; Glotzbach-Schoon, Evelyn; Gerdes, Antje B M; Andreatta, Marta; Müller, Mathias; Mühlberger, Andreas; Pauli, Paul

    2014-01-01

    Extinction is an important mechanism to inhibit initially acquired fear responses. There is growing evidence that the ventromedial prefrontal cortex (vmPFC) inhibits the amygdala and therefore plays an important role in the extinction of delay fear conditioning. To our knowledge, there is no evidence on the role of the prefrontal cortex in the extinction of trace conditioning up to now. Thus, we compared brain structures involved in the extinction of human delay and trace fear conditioning in a between-subjects-design in an fMRI study. Participants were passively guided through a virtual environment during learning and extinction of conditioned fear. Two different lights served as conditioned stimuli (CS); as unconditioned stimulus (US) a mildly painful electric stimulus was delivered. In the delay conditioning group (DCG) the US was administered with offset of one light (CS+), whereas in the trace conditioning group (TCG) the US was presented 4 s after CS+ offset. Both groups showed insular and striatal activation during early extinction, but differed in their prefrontal activation. The vmPFC was mainly activated in the DCG, whereas the TCG showed activation of the dorsolateral prefrontal cortex (dlPFC) during extinction. These results point to different extinction processes in delay and trace conditioning. VmPFC activation during extinction of delay conditioning might reflect the inhibition of the fear response. In contrast, dlPFC activation during extinction of trace conditioning may reflect modulation of working memory processes which are involved in bridging the trace interval and hold information in short term memory. PMID:24904363

  1. Social buffering enhances extinction of conditioned fear responses in male rats.

    Science.gov (United States)

    Mikami, Kaori; Kiyokawa, Yasushi; Takeuchi, Yukari; Mori, Yuji

    2016-09-01

    In social species, the phenomenon in which the presence of conspecific animals mitigates stress responses is called social buffering. We previously reported that social buffering in male rats ameliorated behavioral fear responses, as well as hypothalamic-pituitary-adrenal axis activation, elicited by an auditory conditioned stimulus (CS). However, after social buffering, it is not clear whether rats exhibit fear responses when they are re-exposed to the same CS in the absence of another rat. In the present study, we addressed this issue using an experimental model of extinction. High stress levels during extinction training impaired extinction, suggesting that extinction is enhanced when stress levels during extinction training are low. Therefore, we hypothesized that rats that had received social buffering during extinction training would not show fear responses to a CS, even in the absence of another rat, because social buffering had enhanced the extinction of conditioned fear responses. To test this, we subjected male fear-conditioned rats to extinction training either alone or with a non-conditioned male rat. The subjects were then individually re-exposed to the CS in a recall test. When the subjects individually underwent extinction training, no responses were suppressed in the recall test. Conversely, when the subjects received social buffering during extinction training, freezing and Fos expression in the paraventricular nucleus of the hypothalamus and lateral amygdala were suppressed. Additionally, the effects of social buffering were absent when the recall test was conducted in a different context from the extinction training. The present results suggest that social buffering enhances extinction of conditioned fear responses. PMID:27158024

  2. Pavlov's cockroach: classical conditioning of salivation in an insect.

    Directory of Open Access Journals (Sweden)

    Hidehiro Watanabe

    Full Text Available Secretion of saliva to aid swallowing and digestion is an important physiological function found in many vertebrates and invertebrates. Pavlov reported classical conditioning of salivation in dogs a century ago. Conditioning of salivation, however, has been so far reported only in dogs and humans, and its underlying neural mechanisms remain elusive because of the complexity of the mammalian brain. We previously reported that, in cockroaches Periplaneta americana, salivary neurons that control salivation exhibited increased responses to an odor after conditioning trials in which the odor was paired with sucrose solution. However, no direct evidence of conditioning of salivation was obtained. In this study, we investigated the effects of conditioning trials on the level of salivation. Untrained cockroaches exhibited salivary responses to sucrose solution applied to the mouth but not to peppermint or vanilla odor applied to an antenna. After differential conditioning trials in which an odor was paired with sucrose solution and another odor was presented without pairing with sucrose solution, sucrose-associated odor induced an increase in the level of salivation, but the odor presented alone did not. The conditioning effect lasted for one day after conditioning trials. This study demonstrates, for the first time, classical conditioning of salivation in species other than dogs and humans, thereby providing the first evidence of sophisticated neural control of autonomic function in insects. The results provide a useful model system for studying cellular basis of conditioning of salivation in the simpler nervous system of insects.

  3. Extinction of conditioned fear is better learned and recalled in the morning than in the evening.

    Science.gov (United States)

    Pace-Schott, Edward F; Spencer, Rebecca M C; Vijayakumar, Shilpa; Ahmed, Nafis A K; Verga, Patrick W; Orr, Scott P; Pitman, Roger K; Milad, Mohammed R

    2013-11-01

    Sleep helps emotional memories consolidate and may promote generalization of fear extinction memory. We examined whether extinction learning and memory might differ in the morning and evening due, potentially, to circadian and/or sleep-homeostatic factors. Healthy men (N = 109) in 6 groups completed a 2-session protocol. In Session 1, fear conditioning was followed by extinction learning. Partial reinforcement with mild electric shock produced conditioned skin conductance responses (SCRs) to 2 differently colored lamps (CS+), but not a third color (CS-), within the computer image of a room (conditioning context). One CS+ (CS + E) but not the other (CS + U) was immediately extinguished by un-reinforced presentations in a different room (extinction context). Delay durations of 3 h (within AM or PM), 12 h (morning-to-evening or evening-to-morning) or 24 h (morning-to-morning or evening-to-evening) followed. In Session 2, extinction recall and contextual fear renewal were tested. We observed no significant effects of the delay interval on extinction memory but did observe an effect of time-of-day. Fear extinction was significantly better if learned in the morning (p = .002). Collapsing across CS + type, there was smaller morning differential SCR at both extinction recall (p = .003) and fear renewal (p = .005). Morning extinction recall showed better generalization from the CS + E to CS + U with the response to the CS + U significantly larger than to the CS + E only in the evening (p = .028). Thus, extinction is learned faster and its memory is better generalized in the morning. Cortisol and testosterone showed the expected greater salivary levels in the morning when higher testosterone/cortisol ratio also predicted better extinction learning. Circadian factors may promote morning extinction. Alternatively, evening homeostatic sleep pressure may impede extinction and favor recall of conditioned fear. PMID:23992769

  4. Contextual fear conditioning in virtual reality is affected by 5HTTLPR and NPSR1 polymorphisms: effects on fear-potentiated startle

    Directory of Open Access Journals (Sweden)

    Evelyn Glotzbach-Schoon

    2013-04-01

    Full Text Available The serotonin (5-HT and neuropeptide S (NPS systems are discussed as important genetic modulators of fear and sustained anxiety contributing to the etiology of anxiety disorders. Sustained anxiety is a crucial characteristic of most anxiety disorders which likely develops through context conditioning. This study investigated if and how genetic alterations of the 5-HT and the NPS systems as well as their interaction modulate contextual fear conditioning; specifically, function polymorphic variants in the genes coding for the 5-HT transporter (5HTT and the NPS receptor (NPSR1 were studied. A large group of healthy volunteers was therefore stratified for 5HTTLPR (S+ vs. LL carriers and NPSR1 rs324981 (T+ vs. AA carriers polymorphisms resulting in four genotype groups (S+/T+, S+/AA, LL/T+, LL/AA of 20 participants each. All participants underwent contextual fear conditioning and extinction using a virtual reality paradigm. During acquisition, one virtual office room (anxiety context, CXT+ was paired with an unpredictable electric stimulus (unconditioned stimulus, US, whereas another virtual office room was not paired with any US (safety context, CXT-. During extinction no US was administered. Anxiety responses were quantified by fear-potentiated startle and ratings. Most importantly, we found a gene × gene interaction on fear-potentiated startle. Only carriers of both risk alleles (S+/T+ exhibited higher startle responses in CXT+ compared to CXT-. In contrast, anxiety ratings were only influenced by the NPSR1 polymorphism with AA carriers showing higher anxiety ratings in CXT+ as compared to CXT-. Our results speak in favor of a two level account of fear conditioning with diverging effects on implicit vs. explicit fear responses. Contextual fear reflected in potentiated startle responses may be an endophenotype for anxiety disorders.

  5. Pair exposure with conspecific during fear conditioning induces the link between freezing and passive avoidance behaviors in rats.

    Science.gov (United States)

    Lee, Hyunchan; Noh, Jihyun

    2016-07-01

    Social factor plays an important role in dealing with posttraumatic stress disorder related to excessive physiological fear response and insufficient fear memory extinction of the brain. However, although social circumstances occurred not only during contextual retrieval but also during fear conditioning, most previous studies focused on the advantageous aspects of social buffering in fear retrieval period. To demonstrate the association between fear responses and fear memory from social stimuli during fear conditioning, pair exposed rats with conspecific as social buffering were subjected to a fear conditioning of passive avoidance test to evaluate memory function and freezing behavior. Whereas single exposed rats showed the significant increase of freezing behaviors and passive avoidance behaviors compared to control rats, pair exposed rats showed significant alleviation of the freezing behaviors and passive avoidance behaviors compared to single exposed rats. Furthermore, we determined a significant correlation between freezing and passive avoidance behavioral alteration in pair exposed rats. Taken together, we suggest that pair exposure with conspecific during fear conditioning helps to cope with both freezing response and fear memory systems and their reciprocal interaction has a crucial potential as a resource for the relief of unreasonable stress responses in posttraumatic stress disorder. PMID:26827818

  6. Potentiation rather than distraction in a trace fear conditioning procedure.

    Science.gov (United States)

    Pezze, M A; Marshall, H J; Cassaday, H J

    2016-07-01

    Trace conditioning procedures are defined by the introduction of a trace interval between conditioned stimulus (CS, e.g. noise or light) offset and unconditioned stimulus (US, e.g. footshock). The introduction of an additional stimulus as a distractor has been suggested to increase the attentional demands of the task and to extend the usefulness of the behavioural model. In Experiment 1, the CS was noise and the distractor was provided by an intermittent light. In Experiment 2, the CS was light and the distractor was provided by an intermittent noise. In both experiments, the introduction of a 10s trace interval weakened associative learning compared with that seen in a 0s delay conditioned group. However, there was no consistent evidence of distraction. On the contrary, in Experiment 1, associative learning was stronger (in both trace and delay conditioned groups) for rats conditioned also in the presence of the intermittent light. In Experiment 2, there was no such effect when the roles of the stimuli were reversed. The results of Experiment 2 did however confirm the particular salience of the noise stimulus. The finding of increased associative learning dependent on salience is consistent with arousal-mediated effects on associative learning. PMID:27060226

  7. Abnormal fear conditioning and amygdala processing in an animal model of autism

    DEFF Research Database (Denmark)

    Markram, Kamila; Rinaldi, Tania; La Mendola, Deborah;

    2008-01-01

    -treated animals displayed several symptoms common to autism, among them impaired social interactions and increased repetitive behaviors. Furthermore, VPA-treated rats were more anxious and exhibited abnormally high and longer lasting fear memories, which were overgeneralized and harder to extinguish. On the...... cellular level, the amygdala was hyperreactive to electrical stimulation and displayed boosted synaptic plasticity as well as a deficit in inhibition. We show for the first time enhanced, overgeneralized and resistant conditioned fear memories in an animal model of autism. Such hyperfear could be caused by...

  8. Neural Correlates of Appetitive-Aversive Interactions in Pavlovian Fear Conditioning

    Science.gov (United States)

    Nasser, Helen M.; McNally, Gavan P.

    2013-01-01

    We used Pavlovian counterconditioning in rats to identify the neural mechanisms for appetitive-aversive motivational interactions. In Stage I, rats were trained on conditioned stimulus (CS)-food (unconditioned stimulus [US]) pairings. In Stage II, this appetitive CS was transformed into a fear CS via pairings with footshock. The development of…

  9. A Model of Amygdala-Hippocampal-Prefrontal Interaction in Fear Conditioning and Extinction in Animals

    Science.gov (United States)

    Moustafa, Ahmed A.; Gilbertson, Mark W.; Orr, Scott P.; Herzallah, Mohammad M.; Servatius, Richard J.; Myers, Catherine E.

    2013-01-01

    Empirical research has shown that the amygdala, hippocampus, and ventromedial prefrontal cortex (vmPFC) are involved in fear conditioning. However, the functional contribution of each brain area and the nature of their interactions are not clearly understood. Here, we extend existing neural network models of the functional roles of the hippocampus…

  10. Neonatal Odor-Shock Conditioning Alters the Neural Network Involved in Odor Fear Learning at Adulthood

    Science.gov (United States)

    Sevelinges, Yannick; Sullivan, Regina M.; Messaoudi, Belkacem; Mouly, Anne-Marie

    2008-01-01

    Adult learning and memory functions are strongly dependent on neonatal experiences. We recently showed that neonatal odor-shock learning attenuates later life odor fear conditioning and amygdala activity. In the present work we investigated whether changes observed in adults can also be observed in other structures normally involved, namely…

  11. Bupropion Dose-Dependently Reverses Nicotine Withdrawal Deficits in Contextual Fear Conditioning

    OpenAIRE

    Portugal, George S.; Gould, Thomas J.

    2007-01-01

    Bupropion, a norepinephrine and dopamine reuptake inhibitor and nicotinic acetylcholine receptor antagonist, facilitates smoking cessation and reduces some symptoms of nicotine withdrawal. However, the effects of bupropion on nicotine withdrawal-associated deficits in learning remain unclear. The present study investigated whether bupropion has effects on contextual and cued fear conditioning following withdrawal from chronic nicotine or when administered alone. Bupropion was administered alo...

  12. The Histone Deacetylase Inhibitor Valproic Acid Enhances Acquisition, Extinction, and Reconsolidation of Conditioned Fear

    Science.gov (United States)

    Bredy, Timothy W.; Barad, Mark

    2008-01-01

    Histone modifications contribute to the epigenetic regulation of gene expression, a process now recognized to be important for the consolidation of long-term memory. Valproic acid (VPA), used for many years as an anticonvulsant and a mood stabilizer, has effects on learning and memory and enhances the extinction of conditioned fear through its…

  13. Involvement of the Lateral Septal Area in the Expression of Fear Conditioning to Context

    Science.gov (United States)

    Reis, Daniel G.; Scopinho, America A.; Guimaraes, Francisco S.; Correa, Fernando M. A.; Resstel, Leonardo B. M.

    2010-01-01

    Considering the evidence that the lateral septal area (LSA) modulates defensive responses, the aim of the present study is to verify if this structure is also involved in contextual fear conditioning responses. Neurotransmission in the LSA was reversibly inhibited by bilateral microinjections of cobalt chloride (CoCl[subscript 2], 1 mM) 10 min…

  14. The influence of gonadal hormones on conditioned fear extinction in healthy humans.

    Science.gov (United States)

    Milad, M R; Zeidan, M A; Contero, A; Pitman, R K; Klibanski, A; Rauch, S L; Goldstein, J M

    2010-07-14

    Recent rodent studies suggest that gonadal hormones influence extinction of conditioned fear. Here we investigated sex differences in, and the influence of estradiol and progesterone on, fear extinction in healthy humans. Men and women underwent a two-day paradigm in which fear conditioning and extinction learning took place on day 1 and extinction recall was tested on day 2. Visual cues were used as the conditioned stimuli and a mild electric shock was used as the unconditioned stimulus. Skin conductance was recorded throughout the experiment and used to measure conditioned responses (CRs). Blood samples were obtained from all women to measure estradiol and progesterone levels. We found that higher estradiol during extinction learning enhanced subsequent extinction recall but had no effects on fear acquisition or extinction learning itself. Sex differences were only observed during acquisition, with men exhibiting significantly higher CRs. After dividing women into low- and high-estradiol groups, men showed comparable extinction recall to high-estradiol women, and both of these groups showed higher extinction recall than low-estradiol women. Therefore, sex differences in extinction memory emerged only after taking into account women's estradiol levels. Lower estradiol may impair extinction consolidation in women. These findings could have practical applications in the treatment of anxiety disorders through cognitive and behavioral therapies. PMID:20412837

  15. Blockade of Dopamine Activity in the Nucleus Accumbens Impairs Learning Extinction of Conditioned Fear

    Science.gov (United States)

    Holtzman-Assif, Orit; Laurent, Vincent; Westbrook, R. Frederick

    2010-01-01

    Three experiments used rats to investigate the role of dopamine activity in learning to inhibit conditioned fear responses (freezing) in extinction. In Experiment 1, rats systemically injected with the D2 dopamine antagonist, haloperidol, froze more across multiple extinction sessions and on a drug-free retention test than control rats. In…

  16. A Bout of Voluntary Running Enhances Context Conditioned Fear, Its Extinction, and Its Reconsolidation

    Science.gov (United States)

    Siette, Joyce; Reichelt, Amy C.; Westbrook, R. Frederick

    2014-01-01

    Three experiments used rats to examine the effect of a single bout of voluntary activity (wheel running) on the acquisition, extinction, and reconsolidation of context conditioned fear. In Experiment 1, rats provided with access to a wheel for 3 h immediately before or after a shocked exposure to a context froze more when tested in that context…

  17. Effect of acute Fluoxetine application on a context fear conditioned task in behaviorally restrained rats

    Directory of Open Access Journals (Sweden)

    Laura A . León

    2010-02-01

    Full Text Available In order to study the effect of behavioral or pharmacologically enhanced anxiety on the acquisition of contextual fear conditioning, thirty two Wistar rats (275±25 gm were divided in two groups (behavioral restriction and control. Half of each group received saline solution (ig.; 0.9% or fluoxetine(ig.; 4mg/Kg before the fear conditioning procedure. The two way ANOVA showed significant differences for treatment (F[1,28] = 25.261; P < 0.001. Student Newman-Keuls showed that subjects treated with fluoxetine had lower freezing times. There were no significant differences nor for restriction neither for the interaction between the factors (F[1,28] = 0.115; P = 0.737 y F[1,28] = 0.016; P = 0.899. Thus, the restriction procedure used did not modify the acquisition of the conditioned fear response suggesting that the putative 5-HT enhancement induced is not comparable to that induced by fluoxetine. Acute fluoxetine disrupted the acquisition of the conditioned fear response, suggesting that the mechanism by means of which anxiety disrupts learning could be serotonergic in nature.

  18. Selectivity of conditioned fear of touch is modulated by somatosensory precision.

    Science.gov (United States)

    Harvie, Daniel S; Meulders, Ann; Reid, Emily; Camfferman, Danny; Brinkworth, Russell S A; Moseley, G Lorimer

    2016-06-01

    Learning to initiate defenses in response to specific signals of danger is adaptive. Some chronic pain conditions, however, are characterized by widespread anxiety, avoidance, and pain consistent with a loss of defensive response specificity. Response specificity depends on ability to discriminate between safe and threatening stimuli; therefore, specificity might depend on sensory precision. This would help explain the high prevalence of chronic pain in body areas of low tactile acuity, such as the lower back, and clarify why improving sensory precision may reduce chronic pain. We compared the acquisition and generalization of fear of pain-associated vibrotactile stimuli delivered to either the hand (high tactile acuity) or the back (low tactile acuity). During acquisition, tactile stimulation at one location (CS+) predicted the noxious electrocutaneous stimulation (US), while tactile stimulation at another location (CS-) did not. Responses to three stimuli with decreasing spatial proximity to the CS+ (generalizing stimuli; GS1-3) were tested. Differential learning and generalization were compared between groups. The main outcome of fear-potentiated startle responses showed differential learning only in the hand group. Self-reported fear and expectancy confirmed differential learning and limited generalization in the hand group, and suggested undifferentiated fear and expectancy in the back group. Differences in generalization could not be inferred from the startle data. Specificity of fear responses appears to be affected by somatosensory precision. This has implications for our understanding of the role of sensory imprecision in the development of chronic pain. PMID:26950514

  19. Reinstatement of an Extinguished Fear Conditioned Response in Infant Rats

    Science.gov (United States)

    Revillo, Damian A.; Trebucq, Gastón; Paglini, Maria G.; Arias, Carlos

    2016-01-01

    Although it is currently accepted that the extinction effect reflects new context-dependent learning, this is not so clear during infancy, because some studies did not find recovery of the extinguished conditioned response (CR) in rodents during this ontogenetic stage. However, recent studies have shown the return of an extinguished CR in infant…

  20. Protocol for studying extinction of conditioned fear in naturally cycling female rats.

    Science.gov (United States)

    Maeng, Lisa Y; Cover, Kara K; Landau, Aaron J; Milad, Mohammed R; Lebron-Milad, Kelimer

    2015-01-01

    Extinction of conditioned fear has been extensively studied in male rodents. Recently, there have been an increasing number of studies indicating that neural mechanisms for certain behavioral tasks and response behaviors are different in females and males. Using females in research studies can represent a challenge because of the variation of gonadal hormones during their estrous cycle. This protocol describes well-established procedures that are useful in investigating the role of estrogen in fear extinction memory consolidation in female rats. Phase of the estrous cycle and exogenous estrogen administration prior to extinction training can influence extinction recall 24 hr later. The vaginal swabbing technique for estrous phase identification described here aids the examination and manipulation of naturally cycling gonadal hormones. The use of this basic rodent model may further delineate the mechanisms by which estrogen can modulate fear extinction memory in females. PMID:25741747

  1. CLASSICAL CONDITIONING OF THREE KINDS OF HUMOR IN PUBLICITY

    OpenAIRE

    CAROLINA M. CIFUENTES; JUANITA SÁNCHEZ

    2006-01-01

    Effects of humor in advertisement published in Colombia were investigated in regards to brands,advertisement, purchase intention, recall and recognition.A simultaneous Classical Conditioning procedure was carried out, using Incongruous, Hostile and Allusivehumor associated to three brands. The procedure was applied to 30 university students. Results revealedthat the three kinds of humor work as unconditioning stimulus, generating positive attitudes towardsadvertisement and brand. Humor influe...

  2. Deficient fear conditioning in psychopathy as a function of interpersonal and affective disturbances

    Directory of Open Access Journals (Sweden)

    Ralf eVeit

    2013-10-01

    Full Text Available The diminished fear reactivity is one of the most valid physiological findings in psychopathy research. In a fear conditioning paradigm, with faces as conditioned stimulus (CS and electric shock as unconditioned stimulus (US, we investigated a sample of 14 high psychopathic violent offenders. Event related potentials, skin conductance responses (SCR as well as subjective ratings of the CSs were collected. This study assessed to which extent the different facets of the psychopathy construct contribute to the fear conditioning deficits observed in psychopaths. Participants with high scores on the affective facet subscale of the Psychopathy Checklist-Revised (PCL-R showed weaker conditioned fear responses and lower N100 amplitudes compared to low scorers. In contrast, high scorers on the affective facet rated the CS+ (paired more negatively than low scorers regarding the CS- (unpaired. Regarding the P300, high scores on the interpersonal facet were associated with increased amplitudes to the CS+ compared to the CS-, while the opposed pattern was found with the antisocial facet. Both, the initial and terminal contingent negative variation indicated a divergent pattern: participants with pronounced interpersonal deficits, showed increased cortical negativity to the CS+ compared to the CS-, whereas a reversed CS+/CS- differentiation was found in offenders scoring high on the antisocial facet. The present study revealed that deficient fear conditioning in psychopathy was most pronounced in offenders with high scores on the affective facet. Event related potentials suggest that participants with distinct interpersonal deficits showed increased information processing, whereas the antisocial facet was linked to decreased attention and interest to the CS+. These data indicate that an approach to the facets of psychopathy can help to resolve ambiguous findings in psychopathy research and enables a more precise and useful description of this disorder.

  3. Extinction and Retrieval + Extinction of Conditioned Fear Differentially Activate Medial Prefrontal Cortex and Amygdala in Rats.

    Science.gov (United States)

    Lee, Hongjoo J; Haberman, Rebecca P; Roquet, Rheall F; Monfils, Marie-H

    2015-01-01

    Pairing a previously neutral conditioned stimulus (CS; e.g., a tone) to an aversive unconditioned stimulus (US; e.g., a footshock) leads to associative learning such that the tone alone comes to elicit a conditioned response (e.g., freezing). We have previously shown that an extinction session that occurs within the reconsolidation window (termed retrieval + extinction) attenuates fear responding and prevents the return of fear in Pavlovian fear conditioning (Monfils et al., 2009). To date, the mechanisms that explain the different behavioral outcomes between standard extinction and retrieval + extinction remain poorly understood. Here we sought to examine the differential temporal engagement of specific neural systems by these two approaches using Arc catFISH (cellular compartment analysis of temporal activity using fluorescence in situ hybridization (FISH)). Our results demonstrate that extinction and retrieval + extinction lead to differential patterns of expression, suggesting that they engage different networks. These findings provide insight into the neural mechanisms that allow extinction during reconsolidation to prevent the return of fear in rodents. PMID:26834596

  4. On the scaling of magnetic plasma confinement under classical conditions

    International Nuclear Information System (INIS)

    Present magnetic confinement schemes based on tokamaks and similar devices are characterized by relatively large losses and low beta values. As a consequence, thermonuclear conditions can only be reached in such devices at large linear dimensions or by means of very strong magnetic fields, in combination with large heating powers. This does not rule out the possibility of realizing the same conditions on a smaller scale, i.e. by finding alternative schemes which provide classical and stable confinement of a pure plasma in a closed magnetic bottle. (author)

  5. Rapid learning dynamics in individual honeybees during classical conditioning

    Directory of Open Access Journals (Sweden)

    Evren Pamir

    2014-09-01

    Full Text Available Associative learning in insects has been studied extensively by a multitude of classical conditioning protocols. However, so far little emphasis has been put on the dynamics of learning in individuals. The honeybee is a well-established animal model for learning and memory. We here studied associative learning as expressed in individual behavior based on a large collection of data on olfactory classical conditioning (25 datasets, 3,298 animals. We show that the group-averaged learning curve and memory retention score confound three attributes of individual learning: the ability or inability to learn a given task, the generally fast acquisition of a conditioned response in learners, and the high stability of the conditioned response during consecutive training and memory retention trials. We reassessed the prevailing view that more training results in better memory performance and found that 24h memory retention can be indistinguishable after single-trial and multiple-trial conditioning in individuals. We explain how inter-individual differences in learning can be accommodated within the Rescorla-Wagner theory of associative learning. In both data-analysis and modeling we demonstrate how the conflict between population-level and single-animal perspectives on learning and memory can be disentangled.

  6. Sign-Tracking to an Appetitive Cue Predicts Incubation of Conditioned Fear in Rats

    OpenAIRE

    Morrow, Jonathan D.; Saunders, Benjamin T.; Maren, Stephen; ROBINSON, TERRY E.

    2014-01-01

    Although post-traumatic stress disorder (PTSD) and addiction are very different disorders, both are characterized by hyperreactivity to trauma- or drug-related cues, respectively. We investigated whether an appetitive conditioning task, Pavlovian conditioned approach, which predicts vulnerability to reinstatement of cocaine-seeking, also predicts fear incubation, which may be a marker for vulnerability to PTSD. We classified rats based on whether they learned to approach and interact with a f...

  7. Resting cerebral metabolism correlates with skin conductance and functional brain activation during fear conditioning

    OpenAIRE

    Linnman, Clas; Zeidan, Mohamed A.; Pitman, Roger K.; Milad, Mohammed R.

    2011-01-01

    We investigated whether resting brain metabolism can be used to predict autonomic and neuronal responses during fear conditioning in 20 healthy humans. Regional cerebral metabolic rate for glucose was measured via positron emission tomography at rest. During conditioning, autonomic responses were measured via skin conductance, and blood oxygen level dependent signal was measured via functional magnetic resonance imaging. Resting dorsal anterior cingulate metabolism positively predicted differ...

  8. Sign-tracking to an appetitive cue predicts incubation of conditioned fear in rats.

    Science.gov (United States)

    Morrow, Jonathan D; Saunders, Benjamin T; Maren, Stephen; Robinson, Terry E

    2015-01-01

    Although post-traumatic stress disorder (PTSD) and addiction are very different disorders, both are characterized by hyperreactivity to trauma- or drug-related cues, respectively. We investigated whether an appetitive conditioning task, Pavlovian conditioned approach, which predicts vulnerability to reinstatement of cocaine-seeking, also predicts fear incubation, which may be a marker for vulnerability to PTSD. We classified rats based on whether they learned to approach and interact with a food predictive cue (sign-trackers), or, whether upon cue presentation they went to the location of impending food delivery (goal-trackers). Rats were then exposed to extensive Pavlovian tone-shock pairings, which causes the fear response to increase or "incubate" over time. We found that the fear incubation effect was only present in sign-trackers. The behavior of goal-trackers was more consistent with a normal fear response-it was most robust immediately after training and decayed slowly over time. Sign-trackers also had lower levels of brain-derived neurotrophic factor (BDNF) protein in the prefrontal cortex than goal-trackers. These results indicate that, while many factors likely contribute to the disproportionate co-occurrence of PTSD and substance abuse, one such factor may be a core psychological trait that biases some individuals to attribute excessive motivational significance to predictive cues, regardless of the emotional valence of those cues. High levels of BDNF in the prefrontal cortex may be protective against developing excessive emotional and motivational responses to salient cues. PMID:24747659

  9. Effect of continuous and partial reinforcement on the acquisition and extinction of human conditioned fear.

    Science.gov (United States)

    Grady, Ashley K; Bowen, Kenton H; Hyde, Andrew T; Totsch, Stacie K; Knight, David C

    2016-02-01

    Extinction of Pavlovian conditioned fear in humans is a popular paradigm often used to study learning and memory processes that mediate anxiety-related disorders. Fear extinction studies often only pair the conditioned stimulus (CS) and unconditioned stimulus (UCS) on a subset of acquisition trials (i.e., partial reinforcement/pairing) to prolong extinction (i.e., partial reinforcement extinction effect; PREE) and provide more time to study the process. However, there is limited evidence that the partial pairing procedures typically used during fear conditioning actually extend the extinction process, while there is strong evidence these procedures weaken conditioned response (CR) acquisition. Therefore, determining conditioning procedures that support strong CR acquisition and that also prolong the extinction process would benefit the field. The present study investigated 4 separate CS-UCS pairing procedures to determine methods that support strong conditioning and that also exhibit a PREE. One group (C-C) of participants received continuous CS-UCS pairings; a second group (C-P) received continuous followed by partial CS-UCS pairings; a third group (P-C) received partial followed by continuous CS-UCS pairings; and a fourth group (P-P) received partial CS-UCS pairings during acquisition. A strong skin conductance CR was expressed by C-C and P-C groups but not by C-P and P-P groups at the end of the acquisition phase. The P-C group maintained the CR during extinction. In contrast, the CR extinguished quickly within the C-C group. These findings suggest that partial followed by continuous CS-UCS pairings elicit strong CRs and prolong the extinction process following human fear conditioning. (PsycINFO Database Record PMID:26692449

  10. Resting cerebral metabolism correlates with skin conductance and functional brain activation during fear conditioning.

    Science.gov (United States)

    Linnman, Clas; Zeidan, Mohamed A; Pitman, Roger K; Milad, Mohammed R

    2012-02-01

    We investigated whether resting brain metabolism can be used to predict autonomic and neuronal responses during fear conditioning in 20 healthy humans. Regional cerebral metabolic rate for glucose was measured via positron emission tomography at rest. During conditioning, autonomic responses were measured via skin conductance, and blood oxygen level dependent signal was measured via functional magnetic resonance imaging. Resting dorsal anterior cingulate metabolism positively predicted differentially conditioned skin conductance responses. Midbrain and insula resting metabolism negatively predicted midbrain and insula functional reactivity, while dorsal anterior cingulate resting metabolism positively predicted midbrain functional reactivity. We conclude that resting metabolism in limbic areas can predict some aspects of psychophysiological and neuronal reactivity during fear learning. PMID:22207247

  11. Differentiating the contributions of NMDA receptor-mediated synaptic plasticity in basal and lateral nuclei of the amygdala during Pavlovian fear conditioning

    OpenAIRE

    Sterlace, Sarah Rose

    2014-01-01

    Fear and the development of conditional fear are critical for survival. However, mal-adaptations in the fear system lead to psychiatric disorders such as Post-Traumatic Stress Disorder and anxiety disorders, such as specific phobias. Pavlovian fear conditioning in rodents allows for the study of the neural circuitry and biological mechanisms the underlie fear learning and memory. The basolateral amygdala complex, containing the lateral (LA) and basal (BA) nuclei, are critical for cued and c...

  12. Classical Conditioning with Pulsed Integrated Neural Networks: Circuits and System

    DEFF Research Database (Denmark)

    Lehmann, Torsten

    1998-01-01

    In this paper we investigate on-chip learning for pulsed, integrated neural networks. We discuss the implementational problems the technology imposes on learning systems and we find that abiologically inspired approach using simple circuit structures is most likely to bring success. We develop a...... suitable learning algorithm -- a continuous-time version of a temporal differential Hebbian learning algorithm for pulsed neural systems with non-linear synapses -- as well as circuits for the electronic implementation. Measurements from an experimental CMOS chip are presented. Finally, we use our test...... chip to solve simple classical conditioning tasks, thus verifying the design methodologies put forward in the paper....

  13. Within-session analysis of the extinction of pavlovian fear-conditioning using robust regression

    Directory of Open Access Journals (Sweden)

    Vargas-Irwin, Cristina

    2010-06-01

    Full Text Available Traditionally , the analysis of extinction data in fear conditioning experiments has involved the use of standard linear models, mostly ANOVA of between-group differences of subjects that have undergone different extinction protocols, pharmacological manipulations or some other treatment. Although some studies report individual differences in quantities such as suppression rates or freezing percentages, these differences are not included in the statistical modeling. Withinsubject response patterns are then averaged using coarse-grain time windows which can overlook these individual performance dynamics. Here we illustrate an alternative analytical procedure consisting of 2 steps: the estimation of a trend for within-session data and analysis of group differences in trend as main outcome. This procedure is tested on real fear-conditioning extinction data, comparing trend estimates via Ordinary Least Squares (OLS and robust Least Median of Squares (LMS regression estimates, as well as comparing between-group differences and analyzing mean freezing percentage versus LMS slopes as outcomes

  14. Genetics of PTSD: Fear Conditioning as a Model for Future Research.

    Science.gov (United States)

    Amstadter, Ananda B; Nugent, Nicole R; Koenen, Karestan C

    2009-06-01

    In the last decade, the number of publications in psychiatric genetics has nearly tripled but little attention has been paid to the role of genetic factors in the etiology of posttraumatic stress disorder (PTSD). The present review summarizes the current state of genetic research on PTSD. First, we outline information regarding genetic influences provided by family investigations and by twin studies. Second, we propose the fear-conditioning model of PTSD as a framework for the nomination of candidate genes that may be related to the disorder. Third, we review lines of evidence from three neurobiological systems involved in fear conditioning, and we summarize published investigations of genetic variants studied in association with PTSD in these three systems. Finally, we review gene-by-environment interaction research, a promising novel approach to genetic research in PTSD. PMID:19779593

  15. Genetics of PTSD: Fear Conditioning as a Model for Future Research

    OpenAIRE

    Amstadter, Ananda B.; Nugent, Nicole R.; Koenen, Karestan C.

    2009-01-01

    In the last decade, the number of publications in psychiatric genetics has nearly tripled but little attention has been paid to the role of genetic factors in the etiology of posttraumatic stress disorder (PTSD). The present review summarizes the current state of genetic research on PTSD. First, we outline information regarding genetic influences provided by family investigations and by twin studies. Second, we propose the fear-conditioning model of PTSD as a framework for the nomination of c...

  16. Sex Differences and Chronic Stress Effects on the Neural Circuitry Underlying Fear Conditioning and Extinction

    OpenAIRE

    Farrell, Mollee R.; SENGELAUB, DALE R.; Wellman, Cara L.

    2013-01-01

    There are sex differences in the rates of many stress-sensitive psychological disorders such as post traumatic stress disorder (PTSD). As medial prefrontal cortex and amygdala are implicated in many of these disorders, understanding differential stress effects in these regions may shed light on the mechanisms underlying sex-dependent expression of disorders like depression and anxiety. Prefrontal cortex and amygdala are key regions in the neural circuitry underlying fear conditioning and exti...

  17. Developmental Effects of Acute, Chronic, and Withdrawal from Chronic Nicotine on Fear Conditioning

    OpenAIRE

    Portugal, George S.; Wilkinson, Derek S.; Turner, Jill R.; Blendy, Julie A.; Gould, Thomas J.

    2012-01-01

    Pre-adolescence and adolescence are developmental periods associated with increased vulnerability for tobacco addiction, and exposure to tobacco during these periods may lead to long-lasting changes in behavioral and neuronal plasticity. The present study examined the short- and long-term effects of nicotine and nicotine withdrawal on fear conditioning in pre-adolescent, adolescent, and adult mice, and potential underlying substrates that may mediate the developmental effects of nicotine, suc...

  18. THE IκB KINASE REGULATES CHROMATIN STRUCTURE DURING RECONSOLIDATION OF CONDITIONED FEAR MEMORIES

    OpenAIRE

    Lubin, Farah D.; Sweatt, J. David

    2007-01-01

    Previously formed memories are susceptible to disruption immediately after recall due to a necessity to be reconsolidated after retrieval. Protein translation mechanisms have been widely implicated as being necessary for memory reconsolidation, but gene transcription mechanisms have been much less extensively studied in this context. We found that retrieval of contextual conditioned fear memories activates the NF-κB pathway to regulate histone H3 phosphorylation and acetylation at specific ge...

  19. Classical and quantum initial conditions for Higgs inflation

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    Alberto Salvio

    2015-11-01

    Full Text Available We investigate whether Higgs inflation can occur in the Standard Model starting from natural initial conditions or not. The Higgs has a non-minimal coupling to the Ricci scalar. We confine our attention to the regime where quantum Einstein gravity effects are small in order to have results that are independent of the ultraviolet completion of gravity. At the classical level we find no tuning is required to have successful Higgs inflation, provided the initial homogeneity condition is satisfied. On the other hand, at the quantum level we obtain that the renormalization for large non-minimal coupling requires an additional degree of freedom, unless a tuning of the initial values of the running parameters is made. In order to see that this effect may change the predictions we finally include such degree of freedom in the field content and show that Starobinsky's R2 inflation dominates over Higgs inflation.

  20. Classical and Quantum Initial Conditions for Higgs Inflation

    CERN Document Server

    Salvio, Alberto

    2015-01-01

    We investigate whether Higgs inflation can occur in the Standard Model starting from natural initial conditions or not. The Higgs has a non-minimal coupling to the Ricci scalar. We confine our attention to the regime where quantum Einstein gravity effects are small in order to have results that are independent of the ultraviolet completion of gravity. At the classical level we find no tuning is required to have a successful Higgs inflation, provided the initial homogeneity condition is satisfied. On the other hand, at the quantum level we obtain that the renormalization of the theory for large non-minimal coupling requires an additional degree of freedom that transforms Higgs inflation into Starobinsky $R^2$ inflation, unless a tuning of the initial values of the running parameters is made.

  1. Contextual change after fear acquisition affects conditioned responding and the time course of extinction learning – Implications for renewal research

    Directory of Open Access Journals (Sweden)

    Rachel eSjouwerman

    2015-12-01

    Full Text Available Context plays a central role in retrieving (fear memories. Accordingly, context manipulations are inherent to most return of fear (ROF paradigms (in particular renewal, involving contextual changes after fear extinction. Context changes are, however, also often embedded during earlier stages of ROF experiments such as context changes between fear acquisition and extinction (e.g. in ABC and ABA renewal. Previous studies using these paradigms have however focused exclusively on the context switch after extinction (i.e. renewal. Thus, the possibility of a general effect of a context switch on conditioned responding that may not be conditional to preceding extinction learning remains unstudied.Hence, the current study investigated the impact of a context switch between fear acquisition and extinction on immediate conditioned responding and on the time-course of extinction learning by using a multimodal approach. A group that underwent contextual change after fear conditioning (AB; n = 36 was compared with a group without a contextual change from acquisition to extinction (AA; n = 149, while measuring autonomic (skin conductance and fear potentiated startle measures and subjective fear ratings. Contextual change between fear acquisition and extinction had a pronounced effect on both immediate conditioned responding and on the time course of extinction learning in skin conductance responses and subjective fear ratings. This may have important implications for the mechanisms underlying and the interpretation of the renewal effect (i.e. contextual switch after extinction. Consequently, future studies should incorporate designs and statistical tests that disentangle general effects of contextual change from genuine ROF effects.

  2. Quantum Computer Condition: Stability, Classical Computation and Norms

    CERN Document Server

    Gilbert, G; Thayer, F J; Weinstein, Yu S; Gilbert, Gerald; Hamrick, Michael; Weinstein, Yaakov S.

    2005-01-01

    The Quantum Computer Condition (QCC) provides a rigorous and completely general framework for carrying out analyses of questions pertaining to fault-tolerance in quantum computers. In this paper we apply the QCC to the problem of fluctuations and systematic errors in the values of characteristic parameters in realistic systems. We show that fault-tolerant quantum computation is possible despite variations in these parameters. We also use the QCC to explicitly show that reliable classical computation can be carried out using as input the results of fault-tolerant, but imperfect, quantum computation. Finally, we consider the advantages and disadvantages of the superoperator and diamond norms in connection with application of the QCC to various quantum information-theoretic problems.

  3. CLASSICAL CONDITIONING OF THREE KINDS OF HUMOR IN PUBLICITY

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    CAROLINA M. CIFUENTES

    2006-01-01

    Full Text Available Effects of humor in advertisement published in Colombia were investigated in regards to brands,advertisement, purchase intention, recall and recognition.A simultaneous Classical Conditioning procedure was carried out, using Incongruous, Hostile and Allusivehumor associated to three brands. The procedure was applied to 30 university students. Results revealedthat the three kinds of humor work as unconditioning stimulus, generating positive attitudes towardsadvertisement and brand. Humor influences the purchase intention and recognition, but not the remembranceof brand when compared to neutral advertisement. Incongrous and Hostile Humor generate recognitionand positive attitude towards advertisement and brand. Allusions have a greater effect on purchaseintention than the other ones. Results corroborate the effectiveness of humor as an advertisement tool.

  4. Buchert coarse-graining and the classical energy conditions

    CERN Document Server

    Visser, Matt

    2015-01-01

    So-called "Buchert averaging" is actually a coarse-graining procedure, where fine detail is "smeared out" due to limited spatio-temporal resolution. For technical reasons, (to be explained herein), "averaging" is not really an appropriate term, and I shall consistently describe the process as a "coarse-graining". Because Einstein gravity is nonlinear the coarse-grained Einstein tensor is typically not equal to the Einstein tensor of the coarse-grained spacetime geometry. The discrepancy can be viewed as an "effective" stress-energy, and this "effective" stress-energy often violates the classical energy conditions. To keep otherwise messy technical issues firmly under control, I shall work with conformal-FLRW (CFLRW) cosmologies. These CFLRW-based models are particularly tractable, and are also particularly attractive observationally: the CMB is not distorted. In this CFLRW context one can prove some rigorous theorems regarding the interplay between Buchert coarse-graining, tracelessness of the effective stres...

  5. An Overview of Translationally Informed Treatments for Posttraumatic Stress Disorder: Animal Models of Pavlovian Fear Conditioning to Human Clinical Trials.

    Science.gov (United States)

    Bowers, Mallory E; Ressler, Kerry J

    2015-09-01

    Posttraumatic stress disorder manifests after exposure to a traumatic event and is characterized by avoidance/numbing, intrusive symptoms and flashbacks, mood and cognitive disruptions, and hyperarousal/reactivity symptoms. These symptoms reflect dysregulation of the fear system likely caused by poor fear inhibition/extinction, increased generalization, and/or enhanced consolidation or acquisition of fear. These phenotypes can be modeled in animal subjects using Pavlovian fear conditioning, allowing investigation of the underlying neurobiology of normative and pathological fear. Preclinical studies reveal a number of neurotransmitter systems and circuits critical for aversive learning and memory that have informed the development of therapies used in human clinical trials. In this review, we discuss the evidence for a number of established and emerging pharmacotherapies and device-based treatments for posttraumatic stress disorder that have been developed via a bench to bedside translational model. PMID:26238379

  6. Low levels of estradiol are associated with elevated conditioned responding during fear extinction and with intrusive memories in daily life.

    Science.gov (United States)

    Wegerer, Melanie; Kerschbaum, Hubert; Blechert, Jens; Wilhelm, Frank H

    2014-12-01

    Posttraumatic stress disorder (PTSD) can be conceptualized as a disorder of emotional memory showing strong (conditioned) responses to trauma reminders and intrusive memories among other symptoms. Women are at greater risk of developing PTSD than men. Recent studies have demonstrated an influence of ovarian steroid hormones in both fear conditioning and intrusive memory paradigms. However, although intrusive memories are considered non-extinguished emotional reactions to trauma reminders, none of the previous studies has investigated effects of ovarian hormones on fear conditioning mechanisms and intrusive memories in conjunction. This may have contributed to an overall inconsistent picture of the role of these hormones in emotional learning and memory. To remedy this, we exposed 37 healthy women with a natural menstrual cycle (during early follicular or luteal cycle phase) to a novel conditioned-intrusion paradigm designed to model real-life traumatic experiences. The paradigm included a differential fear conditioning procedure with short violent film clips as unconditioned stimuli. Intrusive memories about the film clips were assessed ambulatorily on subsequent days. Women with lower levels of estradiol displayed elevated differential conditioned skin conductance responding during fear extinction and showed stronger intrusive memories. The inverse relationship between estradiol and intrusive memories was at least partially accounted for by the conditioned responding observed during fear extinction. Progesterone levels were not associated with either fear acquisition/extinction or with intrusive memories. This suggests that lower levels of estradiol might promote stronger symptoms of PTSD through associative processes. PMID:25463649

  7. Odor fear conditioning modifies piriform cortex local field potentials both during conditioning and during post-conditioning sleep.

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    Dylan C Barnes

    Full Text Available BACKGROUND: Sleep plays an active role in memory consolidation. Sleep structure (REM/Slow wave activity [SWS] can be modified after learning, and in some cortical circuits, sleep is associated with replay of the learned experience. While the majority of this work has focused on neocortical and hippocampal circuits, the olfactory system may offer unique advantages as a model system for exploring sleep and memory, given the short, non-thalamic pathway from nose to primary olfactory (piriform cortex, and rapid cortex-dependent odor learning. METHODOLOGY/PRINCIPAL FINDINGS: We examined piriform cortical odor responses using local field potentials (LFPs from freely behaving Long-Evans hooded rats over the sleep-wake cycle, and the neuronal modifications that occurred within the piriform cortex both during and after odor-fear conditioning. We also recorded LFPs from naïve animals to characterize sleep activity in the piriform cortex and to analyze transient odor-evoked cortical responses during different sleep stages. Naïve rats in their home cages spent 40% of their time in SWS, during which the piriform cortex was significantly hypo-responsive to odor stimulation compared to awake and REM sleep states. Rats trained in the paired odor-shock conditioning paradigm developed enhanced conditioned odor evoked gamma frequency activity in the piriform cortex over the course of training compared to pseudo-conditioned rats. Furthermore, conditioned rats spent significantly more time in SWS immediately post-training both compared to pre-training days and compared to pseudo-conditioned rats. The increase in SWS immediately after training significantly correlated with the duration of odor-evoked freezing the following day. CONCLUSIONS/SIGNIFICANCE: The rat piriform cortex is hypo-responsive to odors during SWS which accounts for nearly 40% of each 24 hour period. The duration of slow-wave activity in the piriform cortex is enhanced immediately post-conditioning

  8. The α1 adrenoceptor antagonist prazosin enhances sleep continuity in fear-conditioned Wistar-Kyoto rats

    OpenAIRE

    Laitman, Benjamin M.; Gajewski, Nicholas D.; Mann, Graziella L.; KUBIN, Leszek; Morrison, Adrian R.; Ross, Richard J.

    2013-01-01

    Fragmentation of rapid eye movement sleep (REMS) is well described in individuals with posttraumatic stress disorder (PTSD) and likely has significant functional consequences. Fear-conditioned rodents may offer an attractive model of the changes in sleep that characterize PTSD. Following fear conditioning (FC), Wistar-Kyoto (WKY) rats, a strain known to be particularly stress-sensitive, have increased REMS fragmentation that can be quantified as a shift in the distribution of REMS episodes to...

  9. Limbic areas are functionally decoupled and visual cortex takes a more central role during fear conditioning in humans

    OpenAIRE

    Chrysa Lithari; Stephan Moratti; Nathan Weisz

    2016-01-01

    Going beyond the focus on isolated brain regions (e.g. amygdala), recent neuroimaging studies on fear conditioning point to the relevance of a network of mutually interacting brain regions. In the present MEG study we used Graph Theory to uncover changes in the architecture of the brain functional network shaped by fear conditioning. Firstly, induced power analysis revealed differences in local cortical excitability (lower alpha and beta power) between CS+ and CS− localized to somatosensory c...

  10. Neuropeptide Y input to the rat basolateral amygdala complex and modulation by conditioned fear.

    Science.gov (United States)

    Leitermann, Randy J; Rostkowski, Amanda B; Urban, Janice H

    2016-08-15

    Within the basolateral amygdaloid complex (BLA), neuropeptide Y (NPY) buffers against protracted anxiety and fear. Although the importance of NPY's actions in the BLA is well documented, little is known about the source(s) of NPY fibers to this region. The current studies identified sources of NPY projections to the BLA by using a combination of anatomical and neurochemical approaches. NPY innervation of the BLA was assessed in rats by examining the degree of NPY coexpression within interneurons or catecholaminergic fibers with somatostatin and tyrosine hydroxylase (TH) or dopamine β-hydroxylase (DβH), respectively. Numerous NPY(+) /somatostatin(+) and NPY(+) /somatostatin(-) fibers were observed, suggesting at least two populations of NPY fibers within the BLA. No colocalization was noted between NPY and TH or DβH immunoreactivities. Additionally, Fluorogold (FG) retrograde tracing with immunohistochemistry was used to identify the precise origin of NPY projections to the BLA. FG(+) /NPY(+) cells were identified within the amygdalostriatal transition area (AStr) and stria terminalis and scattered throughout the bed nucleus of the stria terminalis. The subpopulation of NPY neurons in the AStr also coexpressed somatostatin. Subjecting animals to a conditioned fear paradigm increased NPY gene expression within the AStr, whereas no changes were observed within the BLA or stria terminalis. Overall, these studies identified limbic regions associated with stress circuits providing NPY input to the BLA and demonstrated that a unique NPY projection from the AStr may participate in the regulation of conditioned fear. J. Comp. Neurol. 524:2418-2439, 2016. © 2016 Wiley Periodicals, Inc. PMID:26779765

  11. Effect of the coadministration of citalopram with mirtazapine or atipamezole on rat contextual conditioned fear

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    Masuda T

    2014-02-01

    Full Text Available Takahiro Masuda,1,2 Takeshi Inoue,1 Yan An,1 Naoki Takamura,1,3 Shin Nakagawa,1 Yuji Kitaichi,1 Tsukasa Koyama,1 Ichiro Kusumi1 1Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo Japan; 2Medical Affairs, Dainippon Sumitomo Pharma, Co, Ltd, Tokyo, Japan; 3Regenerative and Cellular Medicine Office, Dainippon Sumitomo Pharma, Co, Ltd, Osaka, Japan Background: Mirtazapine, a noradrenergic and specific serotonergic antidepressant, which blocks the α2-adrenergic autoreceptors and heteroreceptors, has shown anxiolytic properties in clinical trials and preclinical animal experiments. The addition of mirtazapine to selective serotonin reuptake inhibitors (SSRIs is clinically suggested to be more effective for anxiety disorders. In this study, we examined the combined effects of mirtazapine and citalopram, an SSRI, on the freezing behavior of rats, which was induced by contextual conditioned fear as an index of anxiety or fear. Methods: Male Sprague Dawley rats individually received footshocks in a shock chamber, and 24 hours later, they were given citalopram and/or mirtazapine injections. One hour after citalopram and 30 minutes after mirtazapine administration, freezing behavior was analyzed in the same shock chamber without shocks. Results: Mirtazapine decreased freezing in a dose-dependent manner, which is consistent with a previous report; it also enhanced an anxiolytic-like effect at a high dose (30 mg/kg of citalopram. Because mirtazapine blocks α2-adrenoreceptors, the combined effect of atipamezole, a selective α2 receptor antagonist, with citalopram was also examined. Similar to mirtazapine, atipamezole reduced freezing dose-dependently, but the enhancement of citalopram's effects by atipamezole was not clear when compared with mirtazapine. Conclusion: The present findings suggest that mirtazapine has an anxiolytic-like effect and may enhance the anxiolytic-like effect of SSRIs, but this enhancement may not be

  12. Long-term memory for pavlovian fear conditioning requires dopamine in the nucleus accumbens and basolateral amygdala.

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    Jonathan P Fadok

    Full Text Available The neurotransmitter dopamine (DA is essential for learning in a pavlovian fear conditioning paradigm known as fear-potentiated startle (FPS. Mice lacking the ability to synthesize DA fail to learn the association between the conditioned stimulus and the fear-inducing footshock. Previously, we demonstrated that restoration of DA synthesis to neurons of the ventral tegmental area (VTA was sufficient to restore FPS. Here, we used a target-selective viral restoration approach to determine which mesocorticolimbic brain regions receiving DA signaling from the VTA require DA for FPS. We demonstrate that restoration of DA synthesis to both the basolateral amygdala (BLA and nucleus accumbens (NAc is required for long-term memory of FPS. These data provide crucial insight into the dopamine-dependent circuitry involved in the formation of fear-related memory.

  13. Using the conditioned fear stress (CFS) animal model to understand the neurobiological mechanisms and pharmacological treatment of anxiety

    OpenAIRE

    Li, Xiaobai

    2012-01-01

    Summary The mechanisms underlying the etiology and pathophysiology of anxiety disorders — the most prevalent class of mental disorders — remain unclear. Over the last 30 years investigators have used the animal model of conditioned fear stress (CFS) to investigate the brain structures and neurotransmitter systems involved in aversive emotional learning and memory. Recent studies have focused on the neuronal circuitry and cellular mechanisms of fearful emotional experiences. This review descri...

  14. A psychological analysis of the effects of memory retrieval prior to extinction on the reacquisition of a conditioned fear association

    OpenAIRE

    Wood, Melissa Allison

    2010-01-01

    The successful reduction of fear is the aim of clinicians treating people with anxiety disorders such as post-traumatic stress disorder or phobias. Existing treatments for these conditions, however, require many treatment sessions and are prone to relapse. A new technique, first demonstrated in rats by Monfils, Cowansage, Klann, & LeDoux (2009) and later shown to be effective in humans (Schiller et al., 2010), provides a method of efficiently reducing fear in a manner which is resistant to va...

  15. Dissociation of learned helplessness and fear conditioning in mice: a mouse model of depression.

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    Dominic Landgraf

    Full Text Available The state of being helpless is regarded as a central aspect of depression, and therefore the learned helplessness paradigm in rodents is commonly used as an animal model of depression. The term 'learned helplessness' refers to a deficit in escaping from an aversive situation after an animal is exposed to uncontrollable stress specifically, with a control/comparison group having been exposed to an equivalent amount of controllable stress. A key feature of learned helplessness is the transferability of helplessness to different situations, a phenomenon called 'trans-situationality'. However, most studies in mice use learned helplessness protocols in which training and testing occur in the same environment and with the same type of stressor. Consequently, failures to escape may reflect conditioned fear of a particular environment, not a general change of the helpless state of an animal. For mice, there is no established learned helplessness protocol that includes the trans-situationality feature. Here we describe a simple and reliable learned helplessness protocol for mice, in which training and testing are carried out in different environments and with different types of stressors. We show that with our protocol approximately 50% of mice develop learned helplessness that is not attributable to fear conditioning.

  16. The role of "interoceptive" fear conditioning in the development of panic disorder.

    Science.gov (United States)

    De Cort, Klara; Griez, Eric; Büchler, Marjolein; Schruers, Koen

    2012-03-01

    More than 20% of the general population experience a panic attack at least once in their lives; however, only a minority goes on to develop panic disorder (PD). Conditioning mechanisms have been proposed to explain this evolution in persons who are susceptible to developing panic disorder upon a "traumatic" panic attack. According to preparedness theory, some cues are more likely to condition than others, namely, those referring to internal, bodily signals of danger. The aim of the present study was to test this theory in a differential conditioning paradigm, making use of scripts referring to different internal, bodily sensations as conditioned stimulus (CS) and inhalation of 35% CO(2) as unconditioned stimulus (UCS). Thirty-three healthy volunteers were assigned to three scripts conditions: "suffocation," "neutral," or "urgency." During acquisition, one of two versions of a particular script was always followed by an inhalation of 35% CO(2) (CS+) and the other by room air (CS-). Acquisition was followed by a test phase, where only inhalations of room air were administered. In line with our hypothesis, only participants in the suffocation condition exhibited a selective conditioning effect. They were more fearful and showed a significantly higher increase in tidal volume than participants in the two control conditions. Results are discussed with relation to interoceptive conditioning, preparedness, and the possible role of tidal volume in PD. PMID:22304891

  17. Immediate Extinction Causes a Less Durable Loss of Performance than Delayed Extinction following Either Fear or Appetitive Conditioning

    Science.gov (United States)

    Woods, Amanda M.; Bouton, Mark E.

    2008-01-01

    Five experiments with rat subjects compared the effects of immediate and delayed extinction on the durability of extinction learning. Three experiments examined extinction of fear conditioning (using the conditioned emotional response method), and two experiments examined extinction of appetitive conditioning (using the food-cup entry method). In…

  18. A NMDA receptor antagonist, MK-801 impairs consolidating extinction of auditory conditioned fear responses in a Pavlovian model.

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    Jun-Li Liu

    Full Text Available BACKGROUND: In auditory fear conditioning, repeated presentation of the tone in the absence of shock leads to extinction of the acquired fear responses. The glutamate N-methyl-D-aspartate receptor (NMDAR is thought to be involved in the extinction of the conditioned fear responses, but its detailed role in initiating and consolidating or maintaining the fear extinction memory is unclear. Here we investigated this issue by using a NMDAR antagonist, MK-801. METHODS/MAIN FINDINGS: The effects of immediate (beginning at 10 min after the conditioning and delayed (beginning at 24 h after conditioning extinctions were first compared with the finding that delayed extinction caused a better and long-lasting (still significant on the 20(th day after extinction depression on the conditioned fear responses. In a second experiment, MK-801 was intraperitoneally (i.p. injected at 40 min before, 4 h or 12 h after the delayed extinction, corresponding to critical time points for initiating, consolidating or maintaining the fear extinction memory. i.p. injection of MK-801 at either 40 min before or 4 h after delayed extinction resulted in an impairment of initiating and consolidating fear extinction memory, which caused a long lasting increased freezing score that was still significant on the 7th day after extinction, compared with extinction group. However, MK-801 administered at 12 h after the delayed extinction, when robust consolidation has been occurred and stabilized, did not affect the established extinction memory. Furthermore, the changed freezing behaviors was not due to an alteration in general anxiety levels, since MK-801 treatment had no effect on the percentage of open-arm time or open-arm entries in an Elevated Plus Maze (EPM task. CONCLUSIONS/SIGNIFICANCE: Our data suggested that the activation of NMDARs plays important role in initiation and consolidation but not maintenance of fear extinction memory. Together with the fact that NMDA receptor is

  19. Fear conditioning in an abdominal pain model: neural responses during associative learning and extinction in healthy subjects.

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    Joswin Kattoor

    Full Text Available Fear conditioning is relevant for elucidating the pathophysiology of anxiety, but may also be useful in the context of chronic pain syndromes which often overlap with anxiety. Thus far, no fear conditioning studies have employed aversive visceral stimuli from the lower gastrointestinal tract. Therefore, we implemented a fear conditioning paradigm to analyze the conditioned response to rectal pain stimuli using fMRI during associative learning, extinction and reinstatement. In N = 21 healthy humans, visual conditioned stimuli (CS(+ were paired with painful rectal distensions as unconditioned stimuli (US, while different visual stimuli (CS(- were presented without US. During extinction, all CSs were presented without US, whereas during reinstatement, a single, unpaired US was presented. In region-of-interest analyses, conditioned anticipatory neural activation was assessed along with perceived CS-US contingency and CS unpleasantness. Fear conditioning resulted in significant contingency awareness and valence change, i.e., learned unpleasantness of a previously neutral stimulus. This was paralleled by anticipatory activation of the anterior cingulate cortex, the somatosensory cortex and precuneus (all during early acquisition and the amygdala (late acquisition in response to the CS(+. During extinction, anticipatory activation of the dorsolateral prefrontal cortex to the CS(- was observed. In the reinstatement phase, a tendency for parahippocampal activation was found. Fear conditioning with rectal pain stimuli is feasible and leads to learned unpleasantness of previously neutral stimuli. Within the brain, conditioned anticipatory activations are seen in core areas of the central fear network including the amygdala and the anterior cingulate cortex. During extinction, conditioned responses quickly disappear, and learning of new predictive cue properties is paralleled by prefrontal activation. A tendency for parahippocampal activation during

  20. Systemic mifepristone blocks reconsolidation of cue-conditioned fear; propranolol prevents this effect.

    Science.gov (United States)

    Pitman, Roger K; Milad, Mohammed R; Igoe, Sarah A; Vangel, Mark G; Orr, Scott P; Tsareva, Alina; Gamache, Karine; Nader, Karim

    2011-08-01

    Reducing reconsolidation of reactivated traumatic memories may offer a novel pharmacological treatment for posttraumatic stress disorder (PTSD). Preclinical research is needed to identify candidate drugs. We evaluated the ability of postreactivation mifepristone (RU38486, a glucocorticoid antagonist), alone and in combination with propranolol (a beta-adrenergic blocker), both given systemically, to reduce cue-conditioned fear in rats. On Day 1, a 30-s tone conditioned stimulus (CS) was paired with an electric shock unconditioned stimulus (US). On Day 2, the CS was presented without the US (reactivation), and the freezing conditioned response (CR) was measured. This was immediately followed by subcutaneous injection of vehicle, mifepristone 30 mg/kg, propranolol 10 mg/kg, or both. On Day 3, the CR was again measured as a test of postreactivation long-term memory (PR-LTM). On Day 10, the CR was again measured to evaluate spontaneous recovery. On Day 11, the US was presented alone (reinstatement). On Day 12, the CR was again measured. A fifth group received mifepristone without the CS presentation (nonreactivation) on Day 2. A sixth group was tested four hours after the Day 2 mifepristone injection to measure postreactivation short-term memory. Postreactivation, but not nonreactivation, mifepristone produced a decrement in the CR that did not undergo spontaneous recovery and underwent only modest reinstatement. Mifepristone did not exert its effect when administered concurrently with propranolol. Postreactivation mifepristone did not impair short-term memory. Systemic mifepristone blocks the reconsolidation of cue-conditioned fear in rats. Concurrent administration of propranolol prevents this effect. Postreactivation mifepristone may be a promising treatment for PTSD, but not necessarily in combination with propranolol. PMID:21688892

  1. Revisiting classical silicate dissolution rate laws under hydrothermal conditions

    Science.gov (United States)

    Pollet-Villard, Marion; Daval, Damien; Saldi, Giuseppe; Knauss, Kevin; Wild, Bastien; Fritz, Bertrand

    2015-04-01

    In the context of geothermal energy, the relative intensities of primary mineral leaching and secondary mineral precipitation can affect porosity and permeability of the reservoir, thereby influencing its hydraulic performance and the efficiency of the geothermal power station. That is why the prediction of reaction kinetics of fluid/rock interactions represents a critical issue in this context. Moreover, in several geothermal systems such as the one of Soultz-sous-Forêts (Alsace, France), the circulation of aqueous fluids induces only modest modifications of their chemical composition. Therefore, fluid-rock interactions take place at close-to-equilibrium conditions, where the rate-affinity relations are poorly known and intensively debated [1]. To describe more precisely the dissolution processes, our strategy consists in investigating the dissolution of the main cleavages of K-spar minerals (one of the prevalent primary minerals in the reservoir of Soultz-sous-Forêts geothermal system) over a wide range of Gibbs free energy (ΔG) conditions. The aims are to decipher the impact of crystallographic orientation and microstructural surface modifications on the dissolution kinetics and to propose a relation between K-spar dissolution rate and ΔG. Our experimental work relies on a coupled approach which combines classical experiments of K-spar dissolution monitored by aqueous chemical analyses (ICP-AES) and innovative techniques of nm- to μm-scale characterization of solid surface (SEM, AFM, VSI) [2]. Our results confirm that K-spar dissolution is an anisotropic process: we measure a tenfold factor between the slowest and the fastest-dissolving surfaces. Moreover, the formation of etch pits on surfaces during their alteration has been evidenced on all of the different faces that have been studied. This complex evolution of the surface topography casts doubt of the relevance of a surface model based on shrinking particles and represents a possible cause of an

  2. Encoding of fear learning and memory in distributed neuronal circuits.

    Science.gov (United States)

    Herry, Cyril; Johansen, Joshua P

    2014-12-01

    How sensory information is transformed by learning into adaptive behaviors is a fundamental question in neuroscience. Studies of auditory fear conditioning have revealed much about the formation and expression of emotional memories and have provided important insights into this question. Classical work focused on the amygdala as a central structure for fear conditioning. Recent advances, however, have identified new circuits and neural coding strategies mediating fear learning and the expression of fear behaviors. One area of research has identified key brain regions and neuronal coding mechanisms that regulate the formation, specificity and strength of fear memories. Other work has discovered critical circuits and neuronal dynamics by which fear memories are expressed through a medial prefrontal cortex pathway and coordinated activity across interconnected brain regions. Here we review these recent advances alongside prior work to provide a working model of the extended circuits and neuronal coding mechanisms mediating fear learning and memory. PMID:25413091

  3. Consequences of adolescent ethanol exposure in male Sprague-Dawley rats on fear conditioning and extinction in adulthood

    Science.gov (United States)

    Broadwater, Margaret A.

    Some evidence suggests that adolescents are more vulnerable than adults to alcohol-induced cognitive deficits and that these deficits may persist into adulthood. Five experiments were conducted to assess long-term consequences of ethanol exposure on tone and context Pavlovian fear conditioning in male Sprague-Dawley rats. Experiment 1 examined age-related differences in sensitivity to ethanol-induced disruptions of fear conditioning to a pre-conditioning ethanol challenge. Experiments 2 examined fear conditioning 22 days after early-mid adolescent (P28-48) or adult (P70-90) exposure to 4 g/kg i.g. ethanol or water given every other day (total of 11 exposures). In Experiment 3, mid-late adolescents (P35-55) were exposed in the same manner to assess whether timing of ethanol exposure within the adolescent period would differentially affect later fear conditioning. Experiment 4 assessed the influence of prior adolescent or adult ethanol exposure on the disrupting effects of a pre-conditioning ethanol challenge. In Experiment 5, neurogenesis (doublecortin---DCX) and cholinergic (choline acetyltransferase---ChAT) markers were measured to assess potential long-term ethanol-induced changes in neural mechanisms important for learning and memory. Results indicated that the long-lasting behavioral effects of ethanol exposure varied depending on exposure age, with early-mid adolescent exposed animals showing attenuated context fear retention (a relatively hippocampal-dependent task), whereas mid-late adolescent and adult exposed animals showed slower context extinction (thought to be reliant on the mPFC). Early-mid adolescent ethanol-exposed animals also had significantly less DCX and ChAT expression than their water-exposed counterparts, possibly contributing to deficits in context fear. Tone fear was not influenced by prior ethanol exposure at any age. In terms of age differences in ethanol sensitivity, adolescents were less sensitive than adults to ethanol

  4. Reduced Electrodermal Fear Conditioning from Ages 3 to 8 Years Is Associated with Aggressive Behavior at Age 8 Years

    Science.gov (United States)

    Gao, Yu; Raine, Adrian; Venables, Peter H.; Dawson, Michael E.; Mednick, Sarnoff A.

    2010-01-01

    Background: Poor fear conditioning characterizes adult psychopathy and criminality, but it is not known whether it is related to aggressive/antisocial behavior in early childhood. Methods: Using a differential, partial reinforcement conditioning paradigm, electrodermal activity was recorded from 200 male and female children at ages 3, 4, 5, 6, and…

  5. Testing conditions in shock-based contextual fear conditioning influence both the behavioral responses and the activation of circuits potentially involved in contextual avoidance.

    Science.gov (United States)

    Viellard, Juliette; Baldo, Marcus Vinicius C; Canteras, Newton Sabino

    2016-12-15

    Previous studies from our group have shown that risk assessment behaviors are the primary contextual fear responses to predatory and social threats, whereas freezing is the main contextual fear response to physically harmful events. To test contextual fear responses to a predator or aggressive conspecific threat, we developed a model that involves placing the animal in an apparatus where it can avoid the threat-associated environment. Conversely, in studies that use shock-based fear conditioning, the animals are usually confined inside the conditioning chamber during the contextual fear test. In the present study, we tested shock-based contextual fear responses using two different behavioral testing conditions: confining the animal in the conditioning chamber or placing the animal in an apparatus with free access to the conditioning compartment. Our results showed that during the contextual fear test, the animals confined to the shock chamber exhibited significantly more freezing. In contrast, the animals that could avoid the conditioning compartment displayed almost no freezing and exhibited risk assessment responses (i.e., crouch-sniff and stretch postures) and burying behavior. In addition, the animals that were able to avoid the shock chamber had increased Fos expression in the juxtadorsomedial lateral hypothalamic area, the dorsomedial part of the dorsal premammillary nucleus and the lateral and dorsomedial parts of the periaqueductal gray, which are elements of a septo/hippocampal-hypothalamic-brainstem circuit that is putatively involved in mediating contextual avoidance. Overall, the present findings show that testing conditions significantly influence both behavioral responses and the activation of circuits involved in contextual avoidance. PMID:27544875

  6. Sex differences in the relationship between maternal fear of pain and children's conditioned pain modulation

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    Evans S

    2013-03-01

    Full Text Available Subhadra Evans, Laura C Seidman, Kirsten C Lung, Lonnie K Zeltzer, Jennie C TsaoPediatric Pain Program, Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USABackground: Parental behaviors, emotions, and cognitions are known to influence children's response to pain. However, prior work has not tested the association between maternal psychological factors and children's responses to a conditioned pain modulation (CPM task. CPM refers to the reduction in perceived pain intensity for a test stimulus following application of a conditioning stimulus to a remote area of the body, and is thought to reflect the descending inhibition of nociceptive signals.Methods: The present study examined sex differences in the association between maternal anxiety about pain and children's CPM responses in 133 healthy children aged 8–17 years. Maternal pain anxiety was assessed using the Pain Anxiety Symptoms Scale-20. In addition to the magnitude of CPM, children's anticipatory anxiety and pain-related fear of the CPM task were measured.Results: Sequential multiple linear regression revealed that even after controlling for child age and general maternal psychological distress, greater maternal pain anxiety was significantly related to greater CPM anticipatory anxiety and pain-related fear in girls, and to less CPM (ie, less pain inhibition in boys.Conclusion: The findings indicate sex-specific relationships between maternal pain anxiety and children's responses to a CPM task over and above that accounted for by the age of the child and the mother's general psychological distress.Keywords: diffuse noxious inhibitory controls, pediatric pain, mother-child relationship, cold pressor, pressure pain, laboratory pain

  7. Repeated exposure to conditioned fear stress increases anxiety and delays sleep recovery following exposure to an acute traumatic stressor

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    Benjamin N Greenwood

    2014-10-01

    Full Text Available Repeated stressor exposure can sensitize physiological responses to novel stressors and facilitate the development of stress-related psychiatric disorders including anxiety. Disruptions in diurnal rhythms of sleep-wake behavior accompany stress-related psychiatric disorders and could contribute to their development. Complex stressors that include fear-eliciting stimuli can be a component of repeated stress experienced by humans, but whether exposure to repeated fear can prime the development of anxiety and sleep disturbances is unknown. In the current study, adult male F344 rats were exposed to either control conditions or repeated contextual fear conditioning for 22 days followed by exposure to either no, mild (10, or severe (100 acute uncontrollable tail shock stress. Exposure to acute stress produced anxiety-like behavior as measured by a reduction in juvenile social exploration and exaggerated shock-elicited freezing in a novel context. Prior exposure to repeated fear enhanced anxiety-like behavior as measured by shock-elicited freezing, but did not alter social exploratory behavior. The potentiation of anxiety produced by prior repeated fear was temporary; exaggerated fear was present 1 day but not 4 days following acute stress. Interestingly, exposure to acute stress reduced REM and NREM sleep during the hours immediately following acute stress. This initial reduction in sleep was followed by robust REM rebound and diurnal rhythm flattening of sleep / wake behavior. Prior repeated fear extended the acute stress-induced REM and NREM sleep loss, impaired REM rebound, and prolonged the flattening of the diurnal rhythm of NREM sleep following acute stressor exposure. These data suggest that impaired recovery of sleep / wake behavior following acute stress could contribute to the mechanisms by which a history of prior repeated stress increases vulnerability to subsequent novel stressors and stress-related disorders.

  8. Increased skin conductance responses and neural activity during fear conditioning are associated with a repressive coping style

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    Tim eKlucken

    2015-06-01

    Full Text Available The investigation of individual differences in coping styles in response to fear conditioning is an important issue for a better understanding of the etiology and treatment of psychiatric disorders. It has been assumed that an avoidant (repressive coping style is characterized by increased emotion regulation efforts in context of fearful stimuli as compared to a more vigilant coping style. However, no study so far has investigated the neural correlates of fear conditioning of repressors and sensitizers.In the present fMRI study, 76 participants were classified as repressors or as sensitizers and were exposed to a fear conditioning paradigm, in which the CS+ predicted electrical stimulation, while another neutral stimulus (CS- did not. In addition, skin conductance responses (SCRs were measured continuously.As the main findings, we found increased neural activations in repressors as compared to sensitizers in the ventromedial prefrontal cortex and the anterior cingulate cortex during fear conditioning. In addition, elevated activity to the CS+ in amygdala, insula, occipital, and orbitofrontal cortex as well as conditioned SCRs were found in repressors.The present results demonstrate increased neural activations in structures linked to emotion down-regulation mechanisms like the ventromedial prefrontal cortex, which may reflect the increased coping effort in repressors. At the same time, repressors showed increased activations in arousal and evaluation-associated structures like the amygdala, the occipital cortex, and the orbitofrontal cortex, which is also mirrored in increased SCRs. The present results support recent assumptions about a two-process model of repression postulating a fast vigilant response to fearful stimuli, but also a second emotion down-regulating process.

  9. Infant rats can learn time intervals before the maturation of the striatum: evidence from odor fear conditioning

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    Julie eBoulanger Bertolus

    2014-05-01

    Full Text Available Interval timing refers to the ability to perceive, estimate and discriminate durations in the range of seconds to minutes. Very little is currently known about the ontogeny of interval timing throughout development. On the other hand, even though the neural circuit sustaining interval timing is a matter of debate, the striatum has been suggested to be an important component of the system and its maturation occurs around the third post-natal week in rats. The global aim of the present study was to investigate interval timing abilities at an age for which striatum is not yet mature. We used odor fear conditioning, as it can be applied to very young animals. In odor fear conditioning, an odor is presented to the animal and a mild footshock is delivered after a fixed interval. Adult rats have been shown to learn the temporal relationships between the odor and the shock after a few associations. The first aim of the present study was to assess the activity of the striatum during odor fear conditioning using 2-Deoxyglucose autoradiography during development in rats. The data showed that although fear learning was displayed at all tested ages, activation of the striatum was observed in adults but not in juvenile animals. Next, we assessed the presence of evidence of interval timing in ages before and after the inclusion of the striatum into the fear conditioning circuit. We used an experimental setup allowing the simultaneous recording of freezing and respiration that have been demonstrated to be sensitive to interval timing in adult rats. This enabled the detection of duration-related temporal patterns for freezing and/or respiration curves in infants as young as 12 days post-natal during odor-fear conditioning. This suggests that infants are able to encode time durations as well as and as quickly as adults while their striatum is not yet functional. Alternative networks possibly sustaining interval timing in infant rats are discussed.

  10. Dynamic competition between large-scale functional networks differentiates fear conditioning and extinction in humans.

    Science.gov (United States)

    Marstaller, Lars; Burianová, Hana; Reutens, David C

    2016-07-01

    The high evolutionary value of learning when to respond to threats or when to inhibit previously learned associations after changing threat contingencies is reflected in dedicated networks in the animal and human brain. Recent evidence further suggests that adaptive learning may be dependent on the dynamic interaction of meta-stable functional brain networks. However, it is still unclear which functional brain networks compete with each other to facilitate associative learning and how changes in threat contingencies affect this competition. The aim of this study was to assess the dynamic competition between large-scale networks related to associative learning in the human brain by combining a repeated differential conditioning and extinction paradigm with independent component analysis of functional magnetic resonance imaging data. The results (i) identify three task-related networks involved in initial and sustained conditioning as well as extinction, and demonstrate that (ii) the two main networks that underlie sustained conditioning and extinction are anti-correlated with each other and (iii) the dynamic competition between these two networks is modulated in response to changes in associative contingencies. These findings provide novel evidence for the view that dynamic competition between large-scale functional networks differentiates fear conditioning from extinction learning in the healthy brain and suggest that dysfunctional network dynamics might contribute to learning-related neuropsychiatric disorders. PMID:27079532

  11. Memory formation for trace fear conditioning requires ubiquitin-proteasome mediated protein degradation in the prefrontal cortex.

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    David S Reis

    2013-10-01

    Full Text Available The cellular mechanisms supporting plasticity during memory consolidation have been a subject of considerable interest. De novo protein and mRNA synthesis in several brain areas are critical, and more recently protein degradation, mediated by the ubiquitin-proteasome system (UPS, has been shown to be important. Previous work clearly establishes a relationship between protein synthesis and protein degradation in the amygdala, but it is unclear whether cortical mechanisms of memory consolidation are similar to those in the amygdala. Recent work demonstrating a critical role for prefrontal cortex (PFC in the acquisition and consolidation of fear memory allows us to address this question. Here we use a PFC-dependent fear conditioning protocol to determine whether UPS mediated protein degradation is necessary for memory consolidation in PFC. Groups of rats were trained with auditory delay or trace fear conditioning and sacrificed 60 min after training. PFC tissue was then analyzed to quantify the amount of polyubiquinated protein. Other animals were trained with similar procedures but were infused with either a proteasome inhibitor (clasto-lactacystin β-lactone or a translation inhibitor (anisomycin in the PFC immediately after training. Our results show increased UPS-mediated protein degradation in the PFC following trace but not delay fear conditioning. Additionally, post-training proteasome or translation inhibition significantly impaired trace but not delay fear memory when tested the next day. Our results further support the idea that the PFC is critical for trace but not delay fear conditioning highlight the role of UPS-mediated degradation as critical for synaptic plasticity.

  12. c-Jun-N-terminal kinase 1 is necessary for nicotine-induced enhancement of contextual fear conditioning.

    Science.gov (United States)

    Leach, Prescott T; Kenney, Justin W; Gould, Thomas J

    2016-08-01

    Acute nicotine enhances hippocampus-dependent learning. Identifying how acute nicotine improves learning will aid in understanding how nicotine facilitates the development of maladaptive memories that contribute to drug-seeking behaviors, help development of medications to treat disorders associated with cognitive decline, and advance understanding of the neurobiology of learning and memory. The effects of nicotine on learning may involve recruitment of signaling through the c-Jun N-terminal kinase family (JNK 1-3). Learning in the presence of acute nicotine increases the transcription of mitogen-activated protein kinase 8 (MAPK8, also known as JNK1), likely through a CREB-dependent mechanism. The functional significance of JNK1 in the effects of acute nicotine on learning, however, is unknown. The current studies undertook a backward genetic approach to determine the functional contribution JNK1 protein makes to nicotine-enhanced contextual fear conditioning. JNK1 wildtype (WT) and knockout (KO) mice were administered acute nicotine prior to contextual and cued fear conditioning. 24h later, mice were evaluated for hippocampus-dependent (contextual fear conditioning) and hippocampus-independent (cued fear conditioning) memory. Nicotine selectively enhanced contextual conditioning in WT mice, but not in KO mice. Nicotine had no effect on hippocampus-independent learning in either genotype. JNK1 KO and WT mice given saline showed similar levels of learning. These data suggest that JNK1 may be recruited by nicotine and is functionally necessary for the acute effects of nicotine on learning and memory. PMID:27235579

  13. Cholinergic Modulation during Acquisition of Olfactory Fear Conditioning Alters Learning and Stimulus Generalization in Mice

    Science.gov (United States)

    Pavesi, Eloisa; Gooch, Allison; Lee, Elizabeth; Fletcher, Max L.

    2013-01-01

    We investigated the role of cholinergic neurotransmission in olfactory fear learning. Mice receiving pairings of odor and foot shock displayed fear to the trained odor the following day. Pretraining injections of the nicotinic antagonist mecamylamine had no effect on subsequent freezing, while the muscarinic antagonist scopolamine significantly…

  14. Modulation of Gene Expression in Contextual Fear Conditioning in the Rat

    Science.gov (United States)

    Macchi, Monica; Ciampini, Cristina; Bernardi, Rodolfo; Baldi, Elisabetta; Bucherelli, Corrado; Brunelli, Marcello; Scuri, Rossana

    2013-01-01

    In contextual fear conditioning (CFC) a single training leads to long-term memory of context-aversive electrical foot-shocks association. Mid-temporal regions of the brain of trained and naive rats were obtained 2 days after conditioning and screened by two-directional suppression subtractive hybridization. A pool of differentially expressed genes was identified and some of them were randomly selected and confirmed with qRT-PCR assay. These transcripts showed high homology for rat gene sequences coding for proteins involved in different cellular processes. The expression of the selected transcripts was also tested in rats which had freely explored the experimental apparatus (exploration) and in rats to which the same number of aversive shocks had been administered in the same apparatus, but temporally compressed so as to make the association between painful stimuli and the apparatus difficult (shock-only). Some genes resulted differentially expressed only in the rats subjected to CFC, others only in exploration or shock-only rats, whereas the gene coding for translocase of outer mitochondrial membrane 20 protein and nardilysin were differentially expressed in both CFC and exploration rats. For example, the expression of stathmin 1 whose transcripts resulted up regulated was also tested to evaluate the transduction and protein localization after conditioning. PMID:24278235

  15. Sex differences in the neurobiology of fear conditioning and extinction: a preliminary fMRI study of shared sex differences with stress-arousal circuitry

    OpenAIRE

    Lebron-Milad Kelimer; Abbs Brandon; Milad Mohammed R; Linnman Clas; Rougemount-Bücking Ansgar; Zeidan Mohammed A; Holt Daphne J; Goldstein Jill M

    2012-01-01

    Abstract Background The amygdala, hippocampus, medial prefrontal cortex (mPFC) and brain-stem subregions are implicated in fear conditioning and extinction, and are brain regions known to be sexually dimorphic. We used functional magnetic resonance imaging (fMRI) to investigate sex differences in brain activity in these regions during fear conditioning and extinction. Methods Subjects were 12 healthy men comparable to 12 healthy women who underwent a 2-day experiment in a 3 T MR scanner. Fear...

  16. Regulation of amygdalar PKA by β-arrestin-2/phosphodiesterase-4 complex is critical for fear conditioning

    OpenAIRE

    Li, Yuting; Li, Haohong; Liu, Xing; Bao, Guobin; Tao, Yezheng; Wu, Ziyan; Xia, Peng; Wu, Chunfu; Li, Baoming; Ma, Lan

    2009-01-01

    β-arrestins, key regulators of receptor signaling, are highly expressed in the central nervous system, but their roles in brain physiology are largely unknown. Here we show that β-arrestin-2 is critically involved in the formation of associative fear memory and amygdalar synaptic plasticity. In response to fear conditioning, β-arrestin-2 translocates to amygdalar membrane where it interacts with PDE-4, a cAMP-degrading enzyme, to inhibit PKA activation. Arrb2−/− mice exhibit impaired conditio...

  17. Histone Modifications around Individual BDNF Gene Promoters in Prefrontal Cortex Are Associated with Extinction of Conditioned Fear

    Science.gov (United States)

    Bredy, Timothy W.; Wu, Hao; Crego, Cortney; Zellhoefer, Jessica; Sun, Yi E.; Barad, Mark

    2007-01-01

    Extinction of conditioned fear is an important model both of inhibitory learning and of behavior therapy for human anxiety disorders. Like other forms of learning, extinction learning is long-lasting and depends on regulated gene expression. Epigenetic mechanisms make an important contribution to persistent changes in gene expression; therefore,…

  18. Trace and Contextual Fear Conditioning Require Neural Activity and NMDA Receptor-Dependent Transmission in the Medial Prefrontal Cortex

    Science.gov (United States)

    Gilmartin, Marieke R.; Helmstetter, Fred J.

    2010-01-01

    The contribution of the medial prefrontal cortex (mPFC) to the formation of memory is a subject of considerable recent interest. Notably, the mechanisms supporting memory acquisition in this structure are poorly understood. The mPFC has been implicated in the acquisition of trace fear conditioning, a task that requires the association of a…

  19. D-Cycloserine Does Not Facilitate Fear Extinction by Reducing Conditioned Stimulus Processing or Promoting Conditioned Inhibition to Contextual Cues

    Science.gov (United States)

    Baker, Kathryn D.; McNally, Gavan P.; Richardson, Rick

    2012-01-01

    The NMDA receptor partial agonist d-cycloserine (DCS) enhances the extinction of learned fear in rats and exposure therapy in humans with anxiety disorders. Despite these benefits, little is known about the mechanisms by which DCS promotes the loss of fear. The present study examined whether DCS augments extinction retention (1) through reductions…

  20. Multimodal assessment of long-term memory recall and reinstatement in a combined cue and context fear conditioning and extinction paradigm in humans.

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    Jan Haaker

    Full Text Available Learning to predict danger via associative learning processes is critical for adaptive behaviour. After successful extinction, persisting fear memories often emerge as returning fear. Investigation of return of fear phenomena, e.g. reinstatement, have only recently began and to date, many critical questions with respect to reinstatement in human populations remain unresolved. Few studies have separated experimental phases in time even though increasing evidence shows that allowing for passage of time (and consolidation between experimental phases has a major impact on the results. In addition, studies have relied on a single psychophysiological dimension only (SCRs/SCL or FPS which hampers comparability between different studies that showed both differential or generalized return of fear following a reinstatement manipulation. In 93 participants, we used a multimodal approach (fear-potentiated startle, skin conductance responses, fear ratings to asses fear conditioning (day 1, extinction (day 2 as well as delayed memory recall and reinstatement (day 8 in a paradigm that probed contextual and cued fear intra-individually. Our findings show persistence of conditioning and extinction memory over time and demonstrate that reinstated fear responses were qualitatively different between dependent variables (subjective fear ratings, FPS, SCRs as well as between cued and contextual CSs. While only the arousal-related measurement (SCRs showed increasing reactions following reinstatement to the cued CSs, no evidence of reinstatement was observed for the subjective ratings and fear-related measurement (FPS. In contrast, for contextual CSs, reinstatement was evident as differential and generalized reinstatement in fear ratings as well as generally elevated physiological fear (FPS and arousal (SCRs related measurements to all contextual CSs (generalized non-differential reinstatement. Returning fear after reinstatement likely depends on a variety of variables

  1. The L-Type Voltage-Gated Calcium Channel Ca[subscript v]1.3 Mediates Consolidation, but Not Extinction, of Contextually Conditioned Fear in Mice

    Science.gov (United States)

    McKinney, Brandon C.; Murphy, Geoffrey G.

    2006-01-01

    Using pharmacological techniques, it has been demonstrated that both consolidation and extinction of Pavlovian fear conditioning are dependent to some extent upon L-type voltage-gated calcium channels (LVGCCs). Although these studies have successfully implicated LVGCCs in Pavlovian fear conditioning, they do not provide information about the…

  2. Induction of c-Fos expression in the mammillary bodies, anterior thalamus and dorsal hippocampus after fear conditioning.

    Science.gov (United States)

    Conejo, Nélida M; González-Pardo, Héctor; López, Matías; Cantora, Raúl; Arias, Jorge L

    2007-09-14

    The aim of the present study was to provide further evidence on the role of particular subdivisions of the mammillary bodies, anterior thalamus and dorsal hippocampus to contextual and auditory fear conditioning. We used c-Fos expression as a marker of neuronal activation to compare rats that received tone-footshock pairings in a distinctive context (conditioned group) to rats being exposed to both the context and the auditory CS without receiving footshocks (unconditioned group), and naïve rats that were only handled. Fos immunoreactivity was significantly increased only in the anterodorsal thalamic nucleus and the lateral mammillary nucleus of the conditioned group. However, the dorsal hippocampus showed the highest density of c-Fos positive nuclei in the naïve group as compared to the other groups. Together, our data support previous studies indicating a particular involvement of the mammillary bodies and anterior thalamus in fear conditioning. PMID:17683804

  3. The protein kinase KIS impacts gene expression during development and fear conditioning in adult mice.

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    Valérie Manceau

    Full Text Available The brain-enriched protein kinase KIS (product of the gene UHMK1 has been shown to phosphorylate the human splicing factor SF1 in vitro. This phosphorylation in turn favors the formation of a U2AF(65-SF1-RNA complex which occurs at the 3' end of introns at an early stage of spliceosome assembly. Here, we analyzed the effects of KIS knockout on mouse SF1 phosphorylation, physiology, adult behavior, and gene expression in the neonate brain. We found SF1 isoforms are differently expressed in KIS-ko mouse brains and fibroblasts. Re-expression of KIS in fibroblasts restores a wild type distribution of SF1 isoforms, confirming the link between KIS and SF1. Microarray analysis of transcripts in the neonate brain revealed a subtle down-regulation of brain specific genes including cys-loop ligand-gated ion channels and metabolic enzymes. Q-PCR analyses confirmed these defects and point to an increase of pre-mRNA over mRNA ratios, likely due to changes in splicing efficiency. While performing similarly in prepulse inhibition and most other behavioral tests, KIS-ko mice differ in spontaneous activity and contextual fear conditioning. This difference suggests that disregulation of gene expression due to KIS inactivation affects specific brain functions.

  4. Ablation of mouse adult neurogenesis alters olfactory bulb structure and olfactory fear conditioning

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    Matthew Valley

    2009-11-01

    Full Text Available Adult neurogenesis replenishes olfactory bulb (OB interneurons throughout the life of most mammals, yet during this constant fl ux it remains unclear how the OB maintains a constant structure and function. In the mouse OB, we investigated the dynamics of turnover and its impact on olfactory function by ablating adult neurogenesis with an x-ray lesion to the subventricular zone (SVZ. Regardless of the magnitude of the lesion to the SVZ, we found no change in the survival of young adult born granule cells (GCs born after the lesion, and a gradual decrease in the population of GCs born before the lesion. After a lesion producing a 96% reduction of incoming adult born GCs to the OB, we found a diminished behavioral fear response to conditioned odor cues but not to audio cues. Interestingly, despite this behavioral defi cit and gradual anatomical changes, we found no electrophysiological changes in the GC population assayed in vivo through dendro-dendritic synaptic plasticity and odor-evoked local fi eld potential oscillations. These data indicate that turnover in the granule cell layer is generally decoupled from the rate of adult neurogenesis, and that OB adult neurogenesis plays a role in a wide behavioral system extending beyond the OB.

  5. Abnormal fear conditioning and amygdala processing in an animal model of autism

    OpenAIRE

    Markram, Kamila; Rinaldi, Tania; La Mendola, Deborah; Sandi, Carmen; Markram, Henry

    2008-01-01

    A core feature of autism spectrum disorders is the impairment in social interactions. Among other brain regions, a deficit in amygdala processing has been suggested to underlie this impairment, but whether the amygdala is processing fear abnormally in autism, is yet not clear. We used the valproic acid (VPA) rat model of autism to (a) screen for autism-like symptoms in rats, (b) test for alterations in amygdala-dependent fear processing, and (c) evaluate neuronal reactivity and synaptic plast...

  6. Nicotinic Receptors in the Dorsal and Ventral Hippocampus Differentially Modulate Contextual Fear Conditioning

    OpenAIRE

    Kenney, Justin W.; Raybuck, Jonathan D.; Gould, Thomas J.

    2012-01-01

    Nicotine administration alters various forms of hippocampus-dependent learning and memory. Increasing work has found that the dorsal and ventral hippocampus differentially contribute to multiple behaviors. Thus, the present study examined whether the effects of nicotine in the dorsal and ventral hippocampus have distinct influences on contextual fear learning in male C57BL/6J mice. Direct infusion of nicotine into the dorsal hippocampus resulted in an enhancement of contextual fear learning, ...

  7. The influence of acute stress on the regulation of conditioned fear

    OpenAIRE

    Raio, Candace M.; Phelps, Elizabeth A.

    2014-01-01

    Fear learning and regulation is a prominent model for describing the pathogenesis of anxiety disorders and stress-related psychopathology. Fear expression can be modulated using a number of regulatory strategies, including extinction, cognitive emotion regulation, avoidance strategies and reconsolidation. In this review, we examine research investigating the effects of acute stress and stress hormones on these regulatory techniques. We focus on what is known about the impact of stress on the ...

  8. Trace and contextual fear conditioning require neural activity and NMDA receptor-dependent transmission in the medial prefrontal cortex

    OpenAIRE

    Gilmartin, Marieke R.; Helmstetter, Fred J.

    2010-01-01

    The contribution of the medial prefrontal cortex (mPFC) to the formation of memory is a subject of considerable recent interest. Notably, the mechanisms supporting memory acquisition in this structure are poorly understood. The mPFC has been implicated in the acquisition of trace fear conditioning, a task that requires the association of a conditional stimulus (CS) and an aversive unconditional stimulus (UCS) across a temporal gap. In both rat and human subjects, frontal regions show increase...

  9. Stress before Puberty Exerts a Sex- and Age-Related Impact on Auditory and Contextual Fear Conditioning in the Rat

    Directory of Open Access Journals (Sweden)

    Maria Toledo-Rodriguez

    2007-01-01

    Full Text Available Adolescence is a period of major physical, hormonal, and psychological changes. It is also characterized by a significant increase in the incidence of psychopathologies and this increase is gender-specific. Stress during adolescence is associated with the development of psychiatric disorders later in life. In this study, we evaluated the impact of psychogenic stress (exposure to predator odor followed by placement on an elevated platform experienced before puberty (days 28–30 on fear memories and hormonal response of male and female rats during adolescence and early adulthood. Stress before puberty impacted in a sex- and age-specific way on the responses to auditory and contextual fear conditioning in adolescence and adulthood: (a increased conditioned fear to the tone in males during adolescence but not during adulthood; (b impaired extinction to the tone in adult males; and (c reduced freezing responses to the context in adolescent females. Stress before puberty did not influence the corticosterone levels 30 minutes after an additional stressor given in adulthood. These results indicate that stress experienced prior to puberty can exert a sex-related differential impact on fear-related behaviors displayed by individuals during late adolescence and early adulthood.

  10. Pre-test metyrapone impairs memory recall in fear conditioning tasks: lack of interaction with β-adrenergic activity

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    Mariella B.L. Careaga

    2015-03-01

    Full Text Available Cognitive processes, such as learning and memory, are essential for our adaptation to environmental changes and consequently for survival. Numerous studies indicate that hormones secreted during stressful situations, such as glucocorticoids (GCs, adrenaline and noradrenaline, regulate memory functions, modulating aversive memory consolidation and retrieval, in an interactive and complementary way. Thus, the facilitatory effects of GCs on memory consolidation as well as their suppressive effects on retrieval are substantially explained by this interaction. On the other hand, low levels of GCs are also associated with negative effects on memory consolidation and retrieval and the mechanisms involved are not well understood. The present study sought to investigate the consequences of blocking the rise of GCs on fear memory retrieval in multiple tests, assessing the participation of β-adrenergic signaling on this effect. Metyrapone (GCs synthesis inhibitor, administered 90 min before the first test of contextual or auditory fear conditioning, negatively affected animals’ performances, but this effect did not persist on a subsequent test, when the conditioned response was again expressed. This result suggested that the treatment impaired fear memory retrieval during the first evaluation. The administration immediately after the first test did not affect the animals’ performances in contextual fear conditioning, suggesting that the drug did not interfere with processes triggered by memory reactivation. Moreover, metyrapone effects were independent of β-adrenergic signaling, since concurrent administration with propranolol, a β-adrenergic antagonist, did not modify the effects induced by metyrapone alone. These results demonstrate that pre-test metyrapone administration led to negative effects on fear memory retrieval and this action was independent of a β-adrenergic signaling.

  11. Classical Belief Conditioning and its Generalization to DSm Theory

    Czech Academy of Sciences Publication Activity Database

    Daniel, Milan

    2008-01-01

    Roč. 2, č. 4 (2008), s. 267-279. ISSN 1752-8917 R&D Projects: GA AV ČR 1ET100300419 Institutional research plan: CEZ:AV0Z10300504 Keywords : belief functions * Dempster-Shafer theory * belief conditioning * DSm theory * overlapping elements * hyper-power set * DSm model Subject RIV: BA - General Mathematics http://www.worldacademicunion.com/journal/jus/jusVol02No4paper04.pdf

  12. Classical Belief Conditioning and its Generalization to DSm Theory

    Czech Academy of Sciences Publication Activity Database

    Daniel, Milan

    San Luis Obispo : California Polytechnic State University, 2007 - (Lee, T.; Liu, Y.; Zhao, X.), s. 596-603 ISSN 1539-2023. - (Series of Information & Management Sciences. 6). [International Conference on Information and Management Sciences /6./. Lhasa (CN), 01.06.2007-06.06.2007] R&D Projects: GA AV ČR 1ET100300419 Institutional research plan: CEZ:AV0Z10300504 Keywords : belief functions * Dempster-Shafer theory * belief conditioning * DSm theory * overlapping elements * hyper-power set * DSm model Subject RIV: BA - General Mathematics

  13. Differences in Memory Development among C57BL/6NCrl, 129S2/SvPasCrl, and FVB/NCrl Mice after Delay and Trace Fear Conditioning

    OpenAIRE

    March, Amelia; Borchelt, David; Golde, Todd; Janus, Christopher

    2014-01-01

    Fear-conditioning testing paradigms have been used to study differences in memory formation between inbred mouse strains, including numerous mouse models of human diseases. In this study, we characterized the conditioned fear memory of 3 inbred strains: C57BL/6NCrl, 129S2/SvPasCrl, and FVB/NCrl, obtained from Charles River Laboratories. We used 2 training paradigms: delay conditioning, in which an unconditional stimulus coterminates with the presentation of a conditional stimulus, and trace c...

  14. Like Extinction, Latent Inhibition of Conditioned Fear in Mice Is Blocked by Systemic Inhibition of L-Type Voltage-Gated Calcium Channels

    Science.gov (United States)

    Blouin, Ashley M.; Cain, Chris K.; Barad, Mike

    2004-01-01

    Having recently shown that extinction of conditioned fear depends on L-type voltage-gated calcium channels (LVGCCs), we have been seeking other protocols that require this unusual induction mechanism. We tested latent inhibition (LI) of fear, because LI resembles extinction except that cue exposures precede, rather than follow, cue-shock pairing.…

  15. Activation of NF-κB in Basolateral Amygdala Is Required for Memory Reconsolidation in Auditory Fear Conditioning

    OpenAIRE

    Si, Jijian; Yang, Jianli; Xue, Lifen; Yang, Chenhao; Luo, Yixiao; Shi, Haishui; Lu, Lin

    2012-01-01

    Posttraumatic stress disorder (PTSD) is characterized by acute and chronic changes in the stress response, manifested as conditioned fear memory. Previously formed memories that are susceptible to disruption immediately after retrieval undergo a protein synthesis-dependent process to become persistent, termed reconsolidation, a process that is regulated by many distinct molecular mechanisms that control gene expression. Increasing evidence supports the participation of the transcription facto...

  16. Reduced Gamma Range Activity at REM Sleep Onset and Termination in Fear-Conditioned Wistar-Kyoto Rats

    OpenAIRE

    Laitman, Benjamin M.; DaSilva, Jamie K.; Ross, Richard J.; Tejani-Butt, Shanaz; Morrison, Adrian R.

    2011-01-01

    Recent investigations of rapid eye movement sleep (REMS) continuity have emphasized the importance of transitions both into and out of REMS. We have previously reported that, compared to Wistar rats (WIS), Wistar-Kyoto rats (WKY) responded to fear conditioning (FC) with more fragmented REMS. Gamma oscillations in the electroencephalogram (EEG) are synchronized throughout the brain in periods of focused attention, and such synchronization of cell assemblies in the brain may represent a tempora...

  17. Blocking of orexin receptors in the paraventricular nucleus of the thalamus has no effect on conditioned fear

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    Yonghui Li

    2015-06-01

    Full Text Available The paraventricular nucleus of the thalamus (PVT projects to the central nucleus of the amygdala and recent experimental evidence indicates a role for the PVT in conditioned fear. Furthermore, the PVT contains a high density of orexin receptors and fibers and acute injections of orexin antagonist into the PVT produce anxiolytic effects. The present study was done to determine if administration of a dual orexin receptor antagonist (DORA in the region of the PVT interfered with the expression of conditioned fear in rats exposed to cued and contextual conditioning paradigms. Infusion of 0.5 µl of the DORA N-biphenyl-2-yl-1-{[(1-methyl-1H-benzimidazol-2yl sulfanyl] acetyl}-L-prolinamide at a concentration of 0.1, 1.0, and 10 nmol had no effect on the freezing produced by exposing rats to an auditory cue or the context associated with foot shock. In contrast, the 1.0 and 10 nmol doses were anxiolytic in the social interaction test. The results of the present study do not support a role for orexin receptors in the PVT in the expression of learned fear. The finding that the 1.0 and 10 nmol doses of DORA in the PVT region were anxiolytic in the social interaction test is consistent with other studies indicating a role for orexins in the PVT in anxiety-like behaviors.

  18. CB1 Cannabinoid Receptors Modulate Kinase and Phosphatase Activity during Extinction of Conditioned Fear in Mice

    Science.gov (United States)

    Kamprath, Kornelia; Hermann, Heike; Lutz, Beat; Marsicano, Giovanni; Cannich, Astrid; Wotjak, Carsten T.

    2004-01-01

    Cannabinoid receptors type 1 (CB1) play a central role in both short-term and long-term extinction of auditory-cued fear memory. The molecular mechanisms underlying this function remain to be clarified. Several studies indicated extracellular signal-regulated kinases (ERKs), the phosphatidylinositol 3-kinase with its downstream effector AKT, and…

  19. Neuronal Correlates of Fear Conditioning in the Bed Nucleus of the Stria Terminalis

    Science.gov (United States)

    Haufler, Darrell; Nagy, Frank Z.; Pare, Denis

    2013-01-01

    Lesion and inactivation studies indicate that the central amygdala (CeA) participates in the expression of cued and contextual fear, whereas the bed nucleus of the stria terminalis (BNST) is only involved in the latter. The basis for this functional dissociation is unclear because CeA and BNST form similar connections with the amygdala and…

  20. Equality conditions for internal entropies of certain classical and quantum models

    CERN Document Server

    Gmeiner, Peter

    2011-01-01

    Mathematical models use information from past observations to generate predictions about the future. If two models make identical predictions the one that needs less information from the past to do this is preferred. It is already known that certain classical models (certain Hidden Markov Models called \\epsilon-machines which are often optimal classical models) are not in general the preferred ones. We extend this result and show that even optimal classical models (models with minimal internal entropy) in general are not the best possible models (called ideal models). Instead of optimal classical models we can construct quantum models which are significantly better but not yet the best possible ones (i.e. they have a strictly smaller internal entropy). In this paper we show conditions when the internal entropies between classical models and specific quantum models coincide. Furthermore it turns out that this situation appears very rarely. An example shows that our results hold only for the specific quantum mo...

  1. Increases in the numerical density of GAT-1 positive puncta in the barrel cortex of adult mice after fear conditioning.

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    Ewa Siucinska

    Full Text Available Three days of fear conditioning that combines tactile stimulation of a row of facial vibrissae (conditioned stimulus, CS with a tail shock (unconditioned stimulus, UCS expands the representation of "trained" vibrissae, which can be demonstrated by labeling with 2-deoxyglucose in layer IV of the barrel cortex. We have also shown that functional reorganization of the primary somatosensory cortex (S1 increases GABAergic markers in the hollows of "trained" barrels of the adult mouse. This study investigated how whisker-shock conditioning (CS+UCS affected the expression of puncta of a high-affinity GABA plasma membrane transporter GAT-1 in the barrel cortex of mice 24 h after associative learning paradigm. We found that whisker-shock conditioning (CS+UCS led to increase expression of neuronal and astroglial GAT-1 puncta in the "trained" row compared to controls: Pseudoconditioned, CS-only, UCS-only and Naïve animals. These findings suggest that fear conditioning specifically induces activation of systems regulating cellular levels of the inhibitory neurotransmitter GABA.

  2. Paradoxical mineralocorticoid receptor-mediated effect in fear memory encoding and expression of rats submitted to an olfactory fear conditioning task.

    Science.gov (United States)

    Souza, Rimenez R; Dal Bó, Silvia; de Kloet, E Ronald; Oitzl, Melly S; Carobrez, Antonio P

    2014-04-01

    There is general agreement that the substantial modification in memory and motivational states exerted by corticosteroids after a traumatic experience is mediated in complementary manner by the mineralocorticoid (MR) and glucocorticoid (GR) receptors. Here we tested the hypothesis that pharmacological manipulation of MR activity would affect behavioral strategy and information storage in an olfactory fear conditioning (OFC) task. Male Wistar rats were submitted to the OFC with different training intensities. We observed that following high intensity OFC acquisition, a set of defensive coping strategies, which includes avoidance and risk assessment behaviors, was elicited when subjects were exposed to the conditioned stimulus (CS) 48 h later. In addition, following either OFC acquisition or retrieval (CS-I test) a profound corticosterone secretion was also detected. Systemic administration of the MR antagonist spironolactone altered the behavioral coping style irrespective the antagonist was administered 60 min prior to the acquisition or before the retrieval session. Surprisingly, the MR agonist fludrocortisone given 60 min prior to acquisition or retrieval of OFC had similar effects as the antagonist. In addition, post-training administration of fludrocortisone, following a weak training procedure, facilitated the consolidation of OFC. Fludrocortisone rather than spironolactone reduced serum corticosterone levels, suggesting that, at least in part, the effects of the MR agonist may derive from additional GR-mediated HPA-axis suppression. In conclusion, the present study suggests the involvement of the MR in the fine-tuning of behavioral adaptation necessary for optimal information storage and expression, as revealed by the marked alterations in the risk assessment behavior. PMID:24296155

  3. On the physical meaning of the gauge conditions of Classical Electromagnetism : the hydrodynamics analogue viewpoint

    OpenAIRE

    Rousseaux, Germain

    2003-01-01

    Based on an analogy between Fluid Mechanics and Electromagnetism, we claim that the gauge conditions of Classical Electromagnetism are not equivalent contrary to the common belief. These "gauges" are usually considered as mathematical conditions that one must specify in order to solve any electromagnetic problem. Here, the author shows that these conditions are physical constraints which can be interpreted as electromagnetic continuity equations. As a consequence, light cannot be considered a...

  4. Maternal condition reduces fear behaviors but not the endocrine response to an emotional threat in virgin female rats.

    Science.gov (United States)

    Agrati, D; Zuluaga, M J; Fernández-Guasti, A; Meikle, A; Ferreira, A

    2008-01-01

    Lactating dams and maternal virgin females are less fearful in behavioral tests compared with non-maternal animals, suggesting that maternal condition per se reduces the negative value of threatening stimuli. In addition, lactating females exhibit a diminished hypothalamic-pituitary-adrenal response to potential environmental threats. Can the maternal condition, independently of the endocrine profile of lactation, promote a reduction in the behavioral as well as in the endocrine response to an emotional stressor? To answer this question, anxiety-related and fear behaviors as well as the levels of corticosterone were evaluated in response to a bright-lit open field-loud noise model in maternal and non-maternal non-ovariectomized virgin females and lactating dams in the presence of the pups. Maternal animals, both lactating and virgin, presented an increased exploration of the bright-lit open field and a significant reduction of fear behaviors, indicated by the decreased flight and immobility responses to the subsequent activation of a loud noise, in comparison to non-maternal virgins. Interestingly, maternal virgin females, as non-maternal rats, showed high corticosterone plasma levels, in contrast to the lower endocrine response exhibited by lactating dams when confronted to this threat. Present results suggest that maternal condition allows females to take risks when caring for their young, a behavioral strategy that is independent of the reduced hypothalamic-pituitary-adrenal axis response characteristic of lactation. This evidence points towards a clear dissociation in the mechanisms regulating behavioral and endocrine responses to emotional stressors during motherhood. PMID:18021777

  5. Long-Term Memory Deficits in Pavlovian Fear Conditioning in Ca2+/Calmodulin Kinase Kinase α-Deficient Mice▿

    OpenAIRE

    Blaeser, Frank; Sanders, Matthew J.; Truong, Nga; Ko, Shanelle; Wu, Long Jun; Wozniak, David F.; Fanselow, Michael S.; Zhuo, Min; Chatila, Talal A.

    2006-01-01

    Signaling by the Ca2+/calmodulin kinase (CaMK) cascade has been implicated in neuronal gene transcription, synaptic plasticity, and long-term memory consolidation. The CaM kinase kinase α (CaMKKα) isoform is an upstream component of the CaMK cascade whose function in different behavioral and learning and memory paradigms was analyzed by targeted gene disruption in mice. CaMKKα mutants exhibited normal long-term spatial memory formation and cued fear conditioning but showed deficits in context...

  6. Rapid Activation of Glucocorticoid Receptors in the Prefrontal Cortex Mediates the Expression of Contextual Conditioned Fear in Rats.

    Science.gov (United States)

    Reis, Fernando M C V; Almada, Rafael C; Fogaça, Manoela V; Brandão, Marcus L

    2016-06-01

    The aim of the present study was to investigate the role of glucocorticoids in medial prefrontal cortex (mPFC) activity and the expression of contextual conditioned fear (freezing). Rats were pretreated with vehicle or metyrapone, a corticosterone synthesis blocker, and exposed to a context previously paired with footshocks. Freezing and Fos-protein expression in different mPFC regions were assessed. Exposure to the aversive context led to increased freezing and Fos expression in the prelimbic (PrL), anterior cingulate areas 1 and 2 (Cg1/Cg2). Pretreatment with metyrapone decreased freezing and Fos expression in these areas. Administration of spironolactone, an MR antagonist, in the PrL before the test decreased freezing. Pretreatment with RU38486, a glucocorticoid receptor (GR) antagonist, reduced this effect of spironolactone, suggesting that the effects of this MR antagonist may be attributable to a redirection of endogenous corticosterone actions to GRs. Consistent with this result, the decrease in freezing that was induced by intra-PrL injections of corticosterone was attenuated by pretreatment with RU38486 but not spironolactone. These findings indicate that corticosterone release during aversive conditioning influences mPFC activity and the retrieval of conditioned fear memory indicating the importance of balance between MR:GR-mediated effects in this brain region in this process. PMID:25976757

  7. Limbic but not non-limbic kindling impairs conditioned fear and promotes plasticity of NPY and its Y2 receptor.

    Science.gov (United States)

    Botterill, J J; Guskjolen, A J; Marks, W N; Caruncho, H J; Kalynchuk, L E

    2015-11-01

    Epileptic seizures negatively affect cognition. However, the mechanisms that contribute to cognitive impairments after seizures are largely unknown. Here, we examined the effects of long-term kindling (i.e., 99 stimulations) of limbic (basolateral amygdala, dorsal hippocampus) and non-limbic (caudate nucleus) brain sites on conditioned fear and hippocampal plasticity. We first showed that kindling had no effect on acquisition of a hippocampal-dependent trace fear-conditioning task but limbic kindling impaired the retrieval of these fear memories. To determine the relationship between memory and hippocampal neuronal activity, we examined the expression of Fos protein 90 min after memory retrieval (i.e., 4 days after the last kindling stimulation). We found that limbic kindling, but not non-limbic kindling, decreased Fos expression in the granule cell layer, hilus, CA3 pyramidal cell layer, and CA1 pyramidal cell layer. Next, to investigate a mechanism that could contribute to dampen hippocampal neuronal activity in limbic-kindled rats, we focused on the endogenous anticonvulsant neuropeptide Y (NPY), which is expressed in a subset of GABAergic interneurons and can prevent glutamate release through interactions with its Y2 receptor. We found that limbic kindling significantly decreased the number of NPY-immunoreactive cells in several hippocampal subfields despite minimal staining of the neurodegenerative marker Fluoro-Jade B. However, we also noted that limbic kindling enhanced NPY immunoreactivity throughout the mossy fiber pathway. In these same regions, we observed limbic kindling-induced de novo expression of the NPY Y2 receptor. These novel findings demonstrate the site-specific effects of kindling on cognition and NPY plasticity, and they provide evidence that altered hippocampal NPY after limbic seizures coincides with dampened neural activity and cognitive impairments. PMID:25146309

  8. The importance of the context in the hippocampus and brain related areas throughout the performance of a fear conditioning task.

    Science.gov (United States)

    Arias, Natalia; Méndez, Marta; Arias, Jorge L

    2015-11-01

    The importance context has been broadly studied in the management of phobias and in the drug addiction literature. The way in which changes to a context influence behavior after the simple acquisition of a passive avoidance task remains unclear. The hippocampus has long been implicated in the contextual and spatial processing required for contextual fear, but its role in encoding the aversive component of a contextual fear memory is still inconclusive. Our work tries to elucidate whether a change in context, represented as differences in the load of the stimuli, is critical for learning about the context-shock association and whether this manipulation of the context could be linked to any change in metabolic brain activity requirements. For this purpose, we used an avoidance conditioning task. Animals were divided into three different experimental conditions. In one group, acquisition was performed in an enriched stimuli environment and retention was performed in a typically lit chamber (the PA-ACQ-CONTX group). In another group, acquisition was performed in the typically lit chamber and retention was undertaken in the highly enriched chamber (the PA-RET-CONTX group). Finally, for the control group, PA-CN-CONTX, acquisition, and retention were performed in the enriched stimuli environment. Our results showed that the PA-ACQ-CONTX group had longer escape latencies and poorer retention than the PA-RET-CONTX and PA-CN-CONTX groups after 24 h of acquisition under contextual changes. To study metabolic brain activity, histochemical labelling of cytochrome c-oxidase (CO) was performed. CO results suggested a neural circuit including the hippocampus, amygdala, thalamus, parahippocampal cortices, and mammillary nuclei that is involved in the learning and memory processes that enable context-dependent behavior. These results highlight how dysfunction in this network may be involved in the contextualization of fear associations that underlie several forms of psychopathology

  9. A Temporal-Specific and Transient cAMP Increase Characterizes Odorant Classical Conditioning

    Science.gov (United States)

    Cui, Wen; Smith, Andrew; Darby-King, Andrea; Harley, Carolyn W.; McLean, John H.

    2007-01-01

    Increases in cyclic adenosine monophosphate (cAMP) are proposed to initiate learning in a wide variety of species. Here, we measure changes in cAMP in the olfactory bulb prior to, during, and following a classically conditioned odor preference trial in rat pups. Measurements were taken up to the point of maximal CREB phosphorylation in olfactory…

  10. Analysis of extinction acquisition to attenuated tones in prenatally stressed and non-stressed offspring following auditory fear conditioning.

    Science.gov (United States)

    Salm, A K; Lally, B E; Borysiewicz, E; Fil, D; Konat, G

    2015-02-01

    Stimulus generalization occurs when stimuli with characteristics similar to a previously conditioned stimulus (CS) become able to evoke a previously conditioned response. Experimental data (Lissek et al., 2005) indicate that patients with post-traumatic stress disorder (PTSD), more often show stimulus generalization following fear conditioning when tested under laboratory conditions. Factors surrounding this observation may contribute to two common features of PTSD: 1) hyper-responsiveness to sensory stimuli reminiscent of those associated with the original trauma, and 2) resistance of PTSD to extinction-based therapies. Adverse early experience is considered a risk factor for the later development of PTSD and in the present experiments we hypothesized that stimulus generalization would occur in an animal model of adverse early experience, the prenatally stressed (PS) rat. Adult PS and control (CON) rats underwent extensive pre-habituation to a conditioning chamber followed by conventional auditory fear conditioning. The next day both groups began an extinction regimen where a series of quieter (attenuated), CSs were administered prior to the full 75 dB training CS. When tested in this manner, PS rats froze at significantly lower tone amplitudes than did CON offspring on the first day of extinction training. This suggests that the PS rats had stimulus-generalized the CS to lower decibel tones. In addition to this finding, we also observed that PS rats froze more often and longer during three ensuing days of extinction training to attenuated tones. Group differences vanished when PS and CON rats were extinguished under conventional conditions. Thus, it appears that the two extinction regimens differed in their aversive cue saliency for the PS vs. CON rats. Follow-up prefrontal cortex transcriptome probing suggests that cholinergic and dopaminergic alterations may be involved. PMID:25449394

  11. Is disgust sensitive to classical conditioning as indexed by facial electromyography and behavioural responses?

    Science.gov (United States)

    Borg, Charmaine; Bosman, Renske C; Engelhard, Iris; Olatunji, Bunmi O; de Jong, Peter J

    2016-06-01

    Earlier studies provided preliminary support for the role of classical conditioning as a pathway of disgust learning, yet this evidence has been limited to self-report. This study included facial electromyographical (EMG) measurements (corrugator and levator muscles) and a behavioural approach task to assess participants' motivation-to-eat the actual food items (conditioned stimuli, CS). Food items served as CS and film excerpts of a woman vomiting served as unconditioned stimuli (US). Following acquisition the CS+ (neutral CS paired with US disgust) was rated as more disgusting and less positive. Notably, the conditioned response was transferred to the actual food items as evidenced by participants' reported lowered willingness-to-eat. Participants also showed heightened EMG activity in response to the CS+ which seemed driven by the corrugator indexing a global negative affect. These findings suggest that classical conditioning as a pathway of disgust learning can be reliably observed in subjective but not in disgust-specific physiological responding. PMID:25818005

  12. The influence of classical-conditioning procedures on subsequent attention to the conditioned brand

    OpenAIRE

    Janiszewski, C; Warlop, Luk

    1993-01-01

    Three experiments are used to investigate the influence of conditioning procedures on attention to a conditioned stimulus. In experiment 1, scenes presented in a sequence that is consistent with prescribed conditioning procedures are shown to encourage attention to the advertised brands in subsequent product displays. Experiment 2 suggests that differential attention to conditioned brands can be attributed to the signaling properties the brand acquires as a consequence of conditioning. Eviden...

  13. Apomorphine-induced pecking in pigeons classically conditioned to environmental cues

    OpenAIRE

    Delius, Juan; Lindenblatt, Ulrike

    1987-01-01

    The dopamine agonist apomorphine elicits protracted pecking when injected systemically (1 mg/kg) into pigeons. In two experiments it was investigated whether apomorphine would function as an unconditioned stimulus in the classical conditioning of pecking in these animals. An experimental design based on a differentiation procedure was used so that possible pseudoconditioning effects were controlled. Two differently coloured test chambers served as negative (CS-) and positive conditioned (CS+)...

  14. Effects of β-Estradiol on Enhanced Conditioned Fear Induced by Single Prolonged Stress and Shock in Rats

    Directory of Open Access Journals (Sweden)

    Ali Rashidy-Pour

    2012-02-01

    Full Text Available Introduction:This study examined the effects of administration of subcutaneous β-estradiol on PTSD-like symptoms (the enhanced conditioned fear response, CFR that induced by a single-prolonged stress (SPS and shock in rats. Methods: Adult male Wistar rats were exposed to SPS procedure: restraint for 2 h, forced swim for 20 min, and ether anesthesia. Then the rats were placed in fear conditioning system and received 1 mA electric foot shock for 4 s. Following, stressed rats injected with β-estradiol (600 μg/kg or sesame oil. For CFR testing, 24 h later animals were re-exposed to the shock chamber for 3-min without further shock application. Percent of freezing was scored. Following testing, the animals were anesthetized and their brains were removed for histological examination (cell count of the hippocampus that stained with cresyl violet. Results: Our results indicated that rats who received electric shock after the SPS exhibited the CFR. β-estradiol significantly reduced the CFR in the SPS rats as compared with control rats. No significant differences were found in cell count in different regions of the hippocampus between experimental groups. Discussion: Our findings indicated that β-estradiol administration after SPS prevents the enhanced CFR in an animal model of PTSD, suggesting a possible role for β-estradiol in the prevention of PTSD

  15. Infusion of lidocaine into the dorsal hippocampus before or after the shock training phase impaired conditioned freezing in a two-phase training task of contextual fear conditioning.

    Science.gov (United States)

    Chang, Shih-Dar; Chen, Der-Yow; Liang, K C

    2008-02-01

    Learning in a contextual fear conditioning task involves forming a context representation and associating it with a shock. The dorsal hippocampus (DH) is implicated in representing the context, but whether it also has a role in associating the context and shock is unclear. To address this issue, male Wistar rats were trained on the task by a two-phase training paradigm, in which rats learned the context representation on day 1 and then reactivated it to associate with the shock on day 2; conditioned freezing was tested on day 3. Lidocaine was infused into the DH at various times in each of the two training sessions. Results showed that intra-DH infusion of lidocaine shortly before or after the context training session on day 1 impaired conditioned freezing, attesting to the DH involvement in context representation. Intra-DH infusion of lidocaine shortly before or after the shock training session on day 2 also impaired conditioned freezing. This deficit was reproduced by infusing lidocaine or APV (alpha-amino-5-phosphonovaleric acid) into the DH after activation of the context memory but before shock administration. The deficit was not due to drug-induced state-dependency, decreased shock sensitivity or reconsolidation failure of the contextual memory. These results suggest that in contextual fear conditioning integrity of the DH is required for memory processing of not only context representation but also context-shock association. PMID:17825588

  16. Switching from Contextual to Tone Fear Conditioning and Vice Versa: The Key Role of the Glutamatergic Hippocampal-Lateral Septal Neurotransmission

    Science.gov (United States)

    Calandreau, Ludovic; Desgranges, Bertrand; Jaffard, Robert; Desmedt, Aline

    2010-01-01

    The aim of the present experiment was to directly assess the role of the glutamatergic hippocampal-lateral septal (HPC-LS) neurotransmission in tone and contextual fear conditioning. We found that pretraining infusion of glutamatergic acid into the lateral septum promotes tone conditioning and concomitantly disrupts contextual conditioning.…

  17. Involvement of dopaminergic and cholinergic systems in social isolation-induced deficits in social affiliation and conditional fear memory in mice.

    Science.gov (United States)

    Okada, R; Fujiwara, H; Mizuki, D; Araki, R; Yabe, T; Matsumoto, K

    2015-07-23

    Post-weaning social isolation rearing (SI) in rodents elicits various behavioral abnormalities including attention deficit hyperactivity disorder-like behaviors. In order to obtain a better understanding of SI-induced behavioral abnormalities, we herein investigated the effects of SI on social affiliation and conditioned fear memory as well as the neuronal mechanism(s) underlying these effects. Four-week-old male mice were group-housed (GH) or socially isolated for 2-4 weeks before the experiments. The social affiliation test and fear memory conditioning were conducted at the age of 6 and 7 weeks, respectively. SI mice were systemically administered saline or test drugs 30 min before the social affiliation test and fear memory conditioning. Contextual and auditory fear memories were elucidated 1 and 4 days after fear conditioning. Social affiliation and contextual and auditory fear memories were weaker in SI mice than in GH mice. Methylphenidate (MPH), an inhibitor for dopamine transporters, ameliorated the SI-induced social affiliation deficit and the effect was attenuated by SCH23390, a D1 receptor antagonist, but not by sulpiride, a D2 receptor antagonist. On the other hand, tacrine, an acetylcholinesterase inhibitor, had no effect on this deficit. In contrast, tacrine improved SI-induced deficits in fear memories in a manner that was reversed by the muscarinic receptor antagonist scopolamine, while MPH had no effect on memory deficits. Neurochemical studies revealed that SI down-regulated the expression levels of the phosphorylated forms of neuro-signaling proteins, calmodulin-dependent kinase II (p-CaMKII), and cyclic AMP-responsive element binding protein (p-CREB), as well as early growth response protein-1 (Egr-1) in the hippocampus. The administration of MPH or tacrine before fear conditioning had no effect on the levels of the phosphorylated forms of the neuro-signaling proteins elucidated following completion of the auditory fear memory test; however

  18. Classical conditioning of sexual arousal in women and men: effects of varying awareness and biological relevance of the conditioned stimulus.

    Science.gov (United States)

    Hoffmann, Heather; Janssen, Erick; Turner, Stefanie L

    2004-02-01

    Classical conditioning of sexual arousal has previously been demonstrated in human males but not in females. This study explored the role of classical (Pavlovian) conditioning in the activation of genital sexual arousal in both women and men, and assessed the effects of varying conditioned stimulus (CS) duration (subliminal/conscious) and relevance (sexually relevant/irrelevant). Twenty-seven female and 29 male participants received either subliminal or conscious presentations of a photograph of either a sexually relevant (abdomen of the opposite sex) or irrelevant (gun) CS+, which was followed by the unconditioned stimulus (US-erotic film clip). A CS-, a stimulus not paired with the US, was also included in the 11 conditioning trials. Ten participants were assigned to a control group that received unpaired presentations of the CS+, CS-, and the US. Both women and men showed more evidence of conditioning to the abdomen than to the gun when the CS was presented subliminally. When consciously perceived CSs were used, however, gender differences emerged. Men again showed the expected cue-to-consequence specificity but women showed the opposite effect, that is, conditioned arousal to the sexually irrelevant rather than to the relevant CS. The latter finding may be due to increased autonomic nervous system arousal associated with the irrelevant CS (gun). Skin conductance responses indicated more general arousal to the gun than to the male abdomen in women. This is the first study to compare the effects of a subliminal and conscious CS and to find classical conditioning of sexual arousal in women. PMID:14739689

  19. Absence of verbal recall or memory for symptom acquisition in fear and trauma exposure: A conceptual case for fear conditioning and learned nonuse in assessment and treatment

    OpenAIRE

    A. Ronald Seifert, PhD

    2012-01-01

    Absence of memory or verbal recall for symptom acquisition in fear and trauma exposure, as well as absence of successful coping behavior for life events, is associated with a number of diagnoses, including traumatic brain injury, posttraumatic stress disorder, pain, and anxiety. The difficulty with diagnosis and treatment planning based on the absence of recall, memory, and successful coping behavior is threefold: (1) these assessments do not distinguish between disruption of behavior and lac...

  20. Conditioned fear and startle magnitude: effects of different footshock or backshock intensities used in training.

    Science.gov (United States)

    Davis, M; Astrachan, D I

    1978-04-01

    In Experiment 1 four groups of rats received 30 light-shock pairings using footshock intensities of either .2, .4, .8, or 1.6 mA. One day later all rats were tested for startle by presenting tones in the presence or absence of the light CS. Potentiated startle (the difference between startle on light-tone vs tone-alone trials) was nonmonotonically related to the shock intensity used in training, with the greatest potentiation at intermediate shock levels. Experiment 3 demonstrated a similar relationship when backshocks instead of footshocks were used. In Experiment 2 rats were trained with either a moderate or high shock and then given an extended extinction-test session 1 day later. The moderate-shock group showed a gradual decline in potentiated startle over extinction. The high-shock group showed a nonmonotonic extinction curve where potentiation progressively increased toward the middle of extinction and dissipated thereafter. The results suggest that acoustic startle bears an inverted U-shaped relationship to fear and are discussed in relation to other studies concerned with this issue. PMID:670892

  1. Sex differences in the neurobiology of fear conditioning and extinction: a preliminary fMRI study of shared sex differences with stress-arousal circuitry

    Directory of Open Access Journals (Sweden)

    Lebron-Milad Kelimer

    2012-04-01

    Full Text Available Abstract Background The amygdala, hippocampus, medial prefrontal cortex (mPFC and brain-stem subregions are implicated in fear conditioning and extinction, and are brain regions known to be sexually dimorphic. We used functional magnetic resonance imaging (fMRI to investigate sex differences in brain activity in these regions during fear conditioning and extinction. Methods Subjects were 12 healthy men comparable to 12 healthy women who underwent a 2-day experiment in a 3 T MR scanner. Fear conditioning and extinction learning occurred on day 1 and extinction recall occurred on day 2. The conditioned stimuli were visual cues and the unconditioned stimulus was a mild electric shock. Skin conductance responses (SCR were recorded throughout the experiment as an index of the conditioned response. fMRI data (blood-oxygen-level-dependent [BOLD] signal changes were analyzed using SPM8. Results Findings showed no significant sex differences in SCR during any experimental phases. However, during fear conditioning, there were significantly greater BOLD-signal changes in the right amygdala, right rostral anterior cingulate (rACC and dorsal anterior cingulate cortex (dACC in women compared with men. In contrast, men showed significantly greater signal changes in bilateral rACC during extinction recall. Conclusions These results indicate sex differences in brain activation within the fear circuitry of healthy subjects despite similar peripheral autonomic responses. Furthermore, we found that regions where sex differences were previously reported in response to stress, also exhibited sex differences during fear conditioning and extinction.

  2. Fear Extinction in Rodents

    OpenAIRE

    Chang, Chun-hui; Knapska, Ewelina; Orsini, Caitlin A.; Rabinak, Christine A.; Zimmerman, Joshua M; Maren, Stephen

    2009-01-01

    Pavlovian conditioning paradigms have become important model systems for understanding the neuroscience of behavior. In particular, studies of the extinction of Pavlovian fear responses are yielding important information about the neural substrates of anxiety disorders in humans. These studies are germane to understanding the neural mechanisms underlying behavioral interventions that suppress fear, including exposure therapy. This chapter described detailed behavioral protocols for examining ...

  3. Maternal separation enhances conditioned fear and decreases the mRNA levels of the neurotensin receptor 1 gene with hypermethylation of this gene in the rat amygdala.

    Directory of Open Access Journals (Sweden)

    Hiroyuki Toda

    Full Text Available Stress during postnatal development is associated with an increased risk for depression, anxiety disorders, and substance abuse later in life, almost as if mental illness is able to be programed by early life stressors. Recent studies suggest that such "programmed" effects can be caused by epigenetic regulation. With respect to conditioned fear, previous studies have indicated that early life stress influences its development in adulthood, whereas no potential role of epigenetic regulation has been reported. Neurotensin (NTS is an endogenous neuropeptide that has receptors densely located in the amygdala and hippocampus. Recently, NTS systems have constituted an emerging target for the treatment of anxiety. The aim of the present work is to clarify whether the NTS system is involved in the disturbance of conditioned fear in rats stressed by maternal separation (MS. The results showed that MS enhanced freezing behaviors in fear-conditioned stress and reduced the gene expression of NTS receptor (NTSR 1 but not of NTS or NTSR2 in the amygdalas of adult rats. The microinjection of a NTSR1 antagonist into the amygdala increased the percentage of freezing in conditioned fear, whereas the microinjection of NTSR1 agonist decreased freezing. These results suggest that NTSR1 in the amygdala may play a role in the effects of MS on conditioned fear stress in adult rats. Moreover, MS increased DNA methylation in the promoter region of NTSR1 in the amygdala. Taken together, MS may leave epigenetic marks in the NTSR1 gene in the amygdala, which may enhance conditioned fear in adulthood. The MS-induced alternations of DNA methylation in the promoter region of NTSR1 in the amygdala may be associated with vulnerability to the development of anxiety disorders and depression in adulthood.

  4. The Amygdala Is Not Necessary for Unconditioned Stimulus Inflation after Pavlovian Fear Conditioning in Rats

    Science.gov (United States)

    Rabinak, Christine A.; Orsini, Caitlin A.; Zimmerman, Joshua M.; Maren, Stephen

    2009-01-01

    The basolateral complex (BLA) and central nucleus (CEA) of the amygdala play critical roles in associative learning, including Pavlovian conditioning. However, the precise role for these structures in Pavlovian conditioning is not clear. Recent work in appetitive conditioning paradigms suggests that the amygdala, particularly the BLA, has an…

  5. Conditions for the quantum-to-classical transition: trajectories versus phase-space distributions.

    Science.gov (United States)

    Greenbaum, Benjamin D; Jacobs, Kurt; Sundaram, Bala

    2007-09-01

    We contrast two sets of conditions that govern the transition in which classical dynamics emerges from the evolution of a quantum system. The first was derived by considering the trajectories seen by an observer (dubbed the "strong" transition) [Bhattacharya et al., Phys. Rev. Lett. 85, 4852 (2000)], and the second by considering phase-space densities (the "weak" transition) [Greenbaum et al., Chaos 15, 033302 (2005)]. On the face of it these conditions appear rather different. We show, however, that in the semiclassical regime, in which the action of the system is large compared to h, and the measurement noise is small, they both offer an essentially equivalent local picture. Within this regime, the weak conditions dominate while in the opposite regime where the action is not much larger than h, the strong conditions dominate. PMID:17930329

  6. Conditions for equality between entanglement-assisted and unassisted classical capacities of a quantum channel

    CERN Document Server

    Shirokov, M E

    2011-01-01

    Both necessary and sufficient conditions of coincidence of the entanglement-assisted capacity with the Holevo capacity of a quantum channel are obtained. By using these conditions the equality between these capacities as well as the strict inequality between them are proved for several classes of quantum channel. In particular, it is shown that coincidence of the entanglement-assisted capacity with the Holevo capacity of a quantum channel implies that the $\\chi$-essential part of this channel is entanglement-breaking (the $\\chi$-essential part is defined as a restriction of a channel obtained by discarding all states useless for transmission of classical information). The above conditions and their corollaries are extended to quantum channels with linear constraints. By using these conditions it is shown that the question of coincidence of the entanglement-assisted capacity with the Holevo capacity of a constrained channel depends on the form of the constraint.

  7. When Two Paradigms Meet: Does Evaluative Learning Extinguish in Differential Fear Conditioning?

    Science.gov (United States)

    Blechert, Jens; Michael, Tanja; Williams, S. Lloyd; Purkis, Helena M.; Wilhelm, Frank H.

    2008-01-01

    Contemporary theories of Pavlovian conditioning propose a distinction between signal learning (SL), in which a conditioned stimulus (CS) becomes a predictor for a biologically significant unconditioned stimulus (US), and evaluative learning (EL), in which the valence of the US is transferred to the CS. This distinction is based largely on the…

  8. Fear conditioning of SCR but not the startle reflex requires conscious discrimination of threat and safety

    NARCIS (Netherlands)

    D. Sevenster; T. Beckers; M. Kindt

    2014-01-01

    There is conflicting evidence as to whether awareness is required for conditioning of the skin conductance response (SCR). Recently, Schultz and Helmstetter (2010) reported SCR conditioning in contingency unaware participants by using difficult to discriminate stimuli. These findings are in stark co

  9. Enhanced fear expression in a psychopathological mouse model of trait anxiety: pharmacological interventions.

    Directory of Open Access Journals (Sweden)

    Simone B Sartori

    Full Text Available The propensity to develop an anxiety disorder is thought to be determined by genetic and environmental factors. Here we investigated the relationship between a genetic predisposition to trait anxiety and experience-based learned fear in a psychopathological mouse model. Male CD-1 mice selectively bred for either high (HAB, or normal (NAB anxiety-related behaviour on the elevated plus maze were subjected to classical fear conditioning. During conditioning both mouse lines showed increased fear responses as assessed by freezing behaviour. However, 24 h later, HAB mice displayed more pronounced conditioned responses to both a contextual or cued stimulus when compared with NAB mice. Interestingly, 6 h and already 1 h after fear conditioning, freezing levels were high in HAB mice but not in NAB mice. These results suggest that trait anxiety determines stronger fear memory and/or a weaker ability to inhibit fear responses in the HAB line. The enhanced fear response of HAB mice was attenuated by treatment with either the α(2,3,5-subunit selective benzodiazepine partial agonist L-838,417, corticosterone or the selective neurokinin-1 receptor antagonist L-822,429. Overall, the HAB mouse line may represent an interesting model (i for identifying biological factors underlying misguided conditioned fear responses and (ii for studying novel anxiolytic pharmacotherapies for patients with fear-associated disorders, including post-traumatic stress disorder and phobias.

  10. Trace classical conditioning in rainbow trout (Oncorhynchus mykiss): what do they learn?

    Science.gov (United States)

    Nordgreen, Janicke; Janczak, Andrew Michael; Hovland, Anne Lene; Ranheim, Birgit; Horsberg, Tor Einar

    2010-03-01

    There are two main memory systems: declarative and procedural memory. Knowledge of these two systems in fish is scarce, and controlled laboratory studies are needed. Trace classical conditioning is an experimentally tractable model of declarative memory. We tested whether rainbow trout (Oncorhynchus mykiss) can learn by trace conditioning and form stimulus-stimulus, as opposed to stimulus-response, associations. We predicted that rainbow trout trained by trace conditioning would show appetitive behaviour (conditioned response; CR) towards the conditioned stimulus (CS; light), and that the CR would be sensitive to devaluation of the unconditioned stimulus (US; food). The learning group (L, N = 14) was trained on a CS + US contingency schedule with a trace interval of 3.4 s. The control group (CtrL, N = 4) was kept on a completely random schedule. The fish that learnt were further trained as either an experimental (L, N = 6) or a memory control (CtrM, N = 3) group. The L group had the US devalued. The CtrM group received only food. No fish in the CtrL group, but nine fish from the L group conditioned to the light. When tested, five L fish changed their CRs after US devaluation, indicating learning by stimulus-stimulus association of the light with the food. CtrM fish retained their original CRs. To the best of our knowledge, this experiment is the first to show that rainbow trout can learn by trace classical conditioning. The results indicate that the fish learnt by 'facts-learning' rather than by reflex acquisition in this study. PMID:19657682

  11. Synaptically released zinc gates long-term potentiation in fear conditioning pathways

    OpenAIRE

    Kodirov, Sodikdjon A.; Takizawa, Shuichi; Joseph, Jamie; Kandel, Eric R.; Shumyatsky, Gleb P.; Bolshakov, Vadim Y.

    2006-01-01

    The functional role of releasable Zn2+ in the central nervous system remains unknown. Here we show that zinc transporter 3 (ZnT-3), which maintains a high concentration of Zn2+ in synaptic vesicles and serves as a marker for zinc-containing neurons, is enriched in the lateral nucleus of the amygdala and in the temporal area 3 of the auditory cortex, an area that conveys information about the auditory conditioned stimulus to the lateral nucleus of the amygdala, but not in other conditioned sti...

  12. Role of the hippocampus in contextual memory after classical aversive conditioning in pigeons (C. livia

    Directory of Open Access Journals (Sweden)

    Reis F.

    1999-01-01

    Full Text Available We investigated the effects of hippocampal lesions with ibotenic acid (IBO on the memory of the sound-context-shock association during reexposure to the conditioning context. Twenty-nine adult pigeons were assigned to a non-lesioned control group (CG, N = 7, a sham-lesioned group (SG, N = 7, a hippocampus-lesioned experimental group (EG, N = 7, and to an unpaired nonlesioned group (tone-alone exposure (NG, N = 8. All pigeons were submitted to a 20-min session in the conditioning chamber with three associations of sound (1000 Hz, 85 dB, 1 s and shock (10 mA, 1 s. Experimental and sham lesions were performed 24 h later (EG and SG when EG birds received three bilateral injections (anteroposterior (A, 4.5, 5.25 and 7.0 of IBO (1 µl and 1 µg/µl and SG received one bilateral injection (A, 5.25 of PBS. The animals were reexposed to the training context 5 days after the lesion. Behavior was videotaped for 20 min and analyzed at 30-s intervals. A significantly higher percent rating of immobility was observed for CG (median, 95.1; range, 79.2 to 100.0 and SG (median, 90.0; range, 69.6 to 95.0 compared to EG (median, 11.62; range, 3.83 to 50.1 and NG (median, 7.33; range, 6.2 to 28.1 (P<0.001 in the training context. These results suggest impairment of contextual fear in birds who received lesions one day after conditioning and a role for the hippocampus in the modulation of emotional aversive memories in pigeons.

  13. A Modified Counterconditioning Procedure Prevents the Renewal of Conditioned Fear in Rats

    Science.gov (United States)

    Thomas, Brian L.; Cutler, Marlo; Novak, Cheryl

    2012-01-01

    Two studies using an ABA design examined the Extinction and renewal of conditioned barpress suppression. Following lights-off and foot shock pairings in Context A, rats were placed in Context B and were given either a standard counterconditioning procedure where the lights-off CS was paired with a novel food US delivered freely or a modified…

  14. Conditional symmetries in axisymmetric quantum cosmologies with scalar fields and the fate of the classical singularities

    Science.gov (United States)

    Zampeli, Adamantia; Pailas, Theodoros; Terzis, Petros A.; Christodoulakis, T.

    2016-05-01

    In this paper, the classical and quantum solutions of some axisymmetric cosmologies coupled to a massless scalar field are studied in the context of minisuperspace approximation. In these models, the singular nature of the Lagrangians entails a search for possible conditional symmetries. These have been proven to be the simultaneous conformal symmetries of the supermetric and the superpotential. The quantization is performed by adopting the Dirac proposal for constrained systems, i.e. promoting the first-class constraints to operators annihilating the wave function. To further enrich the approach, we follow [1] and impose the operators related to the classical conditional symmetries on the wave function. These additional equations select particular solutions of the Wheeler-DeWitt equation. In order to gain some physical insight from the quantization of these cosmological systems, we perform a semiclassical analysis following the Bohmian approach to quantum theory. The generic result is that, in all but one model, one can find appropriate ranges of the parameters, so that the emerging semiclassical geometries are non-singular. An attempt for physical interpretation involves the study of the effective energy-momentum tensor which corresponds to an imperfect fluid.

  15. ApoE Isoform-Dependent Deficits in Extinction of Contextual Fear Conditioning

    OpenAIRE

    Olsen, Reid H. J.; Agam, Mati; Davis, Matthew James; Raber, Jacob

    2012-01-01

    The three major human apoE isoforms (apoE2, apoE3, and apoE4) are encoded by distinct alleles (ε2, ε3, and ε4). Compared to ε3, ε4 is associated with increased risk to develop Alzheimer’s disease (AD), cognitive impairments in Parkinson’s disease (PD), and other conditions. In contrast, a recent study indicated an increased susceptibility to the recurring and re-experiencing symptom cluster of Post Traumatic Stress Disorder (PTSD), as well as related memory impairments, in patients carrying a...

  16. Improvement of memory recall by quercetin in rodent contextual fear conditioning and human early-stage Alzheimer's disease patients.

    Science.gov (United States)

    Nakagawa, Toshiyuki; Itoh, Masanori; Ohta, Kazunori; Hayashi, Yuichi; Hayakawa, Miki; Yamada, Yasushi; Akanabe, Hiroshi; Chikaishi, Tokio; Nakagawa, Kiyomi; Itoh, Yoshinori; Muro, Takato; Yanagida, Daisuke; Nakabayashi, Ryo; Mori, Tetsuya; Saito, Kazuki; Ohzawa, Kaori; Suzuki, Chihiro; Li, Shimo; Ueda, Masashi; Wang, Miao-Xing; Nishida, Emika; Islam, Saiful; Tana; Kobori, Masuko; Inuzuka, Takashi

    2016-06-15

    Patients with Alzheimer's disease (AD) experience a wide array of cognitive deficits, which typically include the impairment of explicit memory. In previous studies, the authors reported that a flavonoid, quercetin, reduces the expression of ATF4 and delays memory deterioration in an early-stage AD mouse model. In the present study, the effects of long-term quercetin intake on memory recall were assessed using contextual fear conditioning in aged wild-type mice. In addition, the present study examined whether memory recall was affected by the intake of quercetin-rich onion (a new cultivar of hybrid onion 'Quergold') powder in early-stage AD patients. In-vivo analysis indicated that memory recall was enhanced in aged mice fed a quercetin-containing diet. Memory recall in early-stage AD patients, determined using the Revised Hasegawa Dementia Scale, was significantly improved by the intake of quercetin-rich onion (Quergold) powder for 4 weeks compared with the intake of control onion ('Mashiro' white onion) powder. These results indicate that quercetin might influence memory recall. PMID:27145228

  17. Repeated Exposure to Conditioned Fear Stress Increases Anxiety and Delays Sleep Recovery Following Exposure to an Acute Traumatic Stressor

    OpenAIRE

    Greenwood, Benjamin N.; Thompson, Robert S.; Opp, Mark R.; Fleshner, Monika

    2014-01-01

    Repeated stressor exposure can sensitize physiological responses to novel stressors and facilitate the development of stress-related psychiatric disorders including anxiety. Disruptions in diurnal rhythms of sleep–wake behavior accompany stress-related psychiatric disorders and could contribute to their development. Complex stressors that include fear-eliciting stimuli can be a component of repeated stress experienced by human beings, but whether exposure to repeated fear can prime the develo...

  18. Nonaware classical conditioning to pictorial facial stimuli in a between-groups paradigm.

    Science.gov (United States)

    Saban, S; Hugdahl, K

    1999-01-01

    The present experiment investigated the effects of aware and nonaware modes of extinction in classical conditioning to facial emotional stimuli. The subjects participated in three different experimental phases. In the first (habituation) phase they were presented with a 500 ms angry face. In the second (acquisition) phase, for half of the subjects the 500 ms face was paired with an aversive noise (experimental group) while for the other half of the subjects the face and the noise presentations were separated by 6-10 s intervals (sensitization control group). In the third (extinction) phase, these two groups were further divided into two subgroups. One subgroup of both the experimental and control group had the face stimulus presented for 30 ms, and immediately masked with a neutral picture. The other two subgroups had the face presented for 500 ms with no mask. The results showed that conditioning only occurred in the experimental subgroups which was indicated by a significant difference between skin conductance responses during habituation and corresponding responses during extinction. Secondly, comparing the experimental and control groups during the extinction phase, a significant conditioning effect was observed for both the aware and nonaware masked modes of extinction for the experimental group. The results suggest that conditioned autonomic responses may be elicited in a nonaware mode. PMID:10381162

  19. Association between oxidative stress and contextual fear conditioning in Carioca high- and low-conditioned freezing rats.

    Science.gov (United States)

    Hassan, Waseem; Gomes, Vitor de Castro; Pinton, Simone; Batista Teixeira da Rocha, Joao; Landeira-Fernandez, J

    2013-05-28

    We recently reported two novel breeding lines of rats known as Carioca high-and low-conditioned freezing (CHF and CLF), based on defensive freezing responses to contextual cues previously associated with electric footshock. The anxiety-like profile of these animals from the 7th generation was tested in the elevated plus maze. The results indicated that CHF animals presented a significantly more "anxious" phenotype compared with CLF animals. Animals from the 12th generation were used to evaluate the oxidative stress status of the cortex, hippocampus, and cerebellum. Reactive oxidative species (ROS) were evaluated using 2,7-dichlorofluorescin diacetate (DCFH-DA; a sensor of reactive oxygen species [ROS]), and the levels of malondialdehyde (MDA), an early marker of lipid peroxidation, were assessed. The results indicated that free radical concentrations and MDA levels were significantly higher in all three brain structures in CHF rats compared with CLF rats. Our data also showed that the hippocampus had the highest reactive species and MDA concentrations compared with the cortex and cerebellum in CHF rats. Animals from the 16th generation were used to evaluate the antioxidant enzyme activity of catalase (CAT) and glutathione peroxidase (GPx) within these three brain structures. The results indicated that CAT activity was lower in the cortex and hippocampus in CHF rats compared with CLF rats. No significant difference was observed in the cerebellum. The enzymatic activity of GPx was significantly decreased in all three structures in CHF rats compared with CLF rats. The hippocampus exhibited the highest GPx activity compared with the other two brain structures. These findings suggest the involvement of a redox system in these two bidirectional lines, and the hippocampus might be one of the prime brain structures involved in this state of oxidative stress imbalance. PMID:23566816

  20. Different Mechanisms of Fear Extinction Dependent on Length of Time since Fear Acquisition

    Science.gov (United States)

    Davis, Michael; Myers, Karyn M.; Ressler, Kerry J.

    2006-01-01

    Fear extinction is defined as a decline in conditioned fear responses (CRs) following nonreinforced exposure to a feared conditioned stimulus (CS). Behavioral evidence indicates that extinction is a form of inhibitory learning: Extinguished fear responses reappear with the passage of time (spontaneous recovery), a shift of context (renewal), and…

  1. Long-term memory of visually cued fear conditioning: roles of the neuronal nitric oxide synthase gene and cyclic AMP response element-binding protein.

    Science.gov (United States)

    Kelley, J B; Anderson, K L; Altmann, S L; Itzhak, Y

    2011-02-01

    Nitric oxide (NO) produced by neuronal nitric oxide synthase (nNOS) has a role in late-phase long-term potentiation (LTP) and long-term memory (LTM) formation. Our recent studies implicated NO signaling in contextual and auditory cued fear conditioning. The present study investigated the role of NO signaling in visually cued fear conditioning. First, visually cued fear conditioning was investigated in wild-type (WT) and nNOS knockout (KO) mice. Second, the effects of pharmacological modulators of NO signaling on the acquisition of visually cued fear conditioning were investigated. Third, plasma levels of corticosterone were measured to determine a relationship between physiological and behavioral responses to fear conditioning. Fourth, levels of extracellular signal-related kinase (ERK1/2) and cyclic AMP response element binding protein (CREB) phosphorylation, downstream of NO signaling, were determined in the amygdala as potential correlates of fear learning. Mice underwent single or multiple (4) spaced trainings that consisted of a visual cue (blinking light) paired with footshock. WT mice acquired cued and contextual LTM following single and multiple trainings. nNOS KO mice acquired neither cued nor contextual LTM following a single training; however, multiple trainings improved contextual but not cued LTM. The selective nNOS inhibitor S-methyl-thiocitrulline (SMTC) impaired cued and contextual LTM in WT mice. The NO donor molsidomine recovered contextual LTM but had no effect on cued LTM in nNOS KO mice. Re-exposure to the visual cue 24 h posttraining elicited freezing response and a marked increase in plasma corticosterone levels in WT but not nNOS KO mice. The expression of CREB phosphorylation (Ser-133) was significantly higher in naive nNOS KO mice than in WT counterparts, and pharmacological modulators of NO had significant effects on levels of CREB phosphorylation and expression. These findings suggest that visual cue-dependent LTM is impaired in nNOS KO

  2. The use of cognitive enhancers in animal models of fear extinction.

    Science.gov (United States)

    Kaplan, Gary B; Moore, Katherine A

    2011-08-01

    In anxiety disorders, such as posttraumatic stress disorders and phobias, classical conditioning pairs natural (unconditioned) fear-eliciting stimuli with contextual or discrete cues resulting in enduring fear responses to multiple stimuli. Extinction is an active learning process that results in a reduction of conditioned fear responses after conditioned stimuli are no longer paired with unconditioned stimuli. Fear extinction often produces incomplete effects and this highlights the relative permanence of bonds between conditioned stimuli and conditioned fear responses. The animal research literature is rich in its demonstration of cognitive enhancing agents that alter fear extinction. This review specifically examines the fear extinguishing effects of cognitive enhancers that act on gamma-aminobutyric acid (GABA), glutamatergic, cholinergic, adrenergic, dopaminergic, and cannabinoid signaling pathways. It also examines the effects of compounds that alter epigenetic and neurotrophic mechanisms in fear extinction. Of these cognitive enhancers, glutamatergic N-methyl d-aspartate (NMDA) receptor agonists, such as D-cycloserine, have enhanced fear extinction in a context-, dose- and time-dependent manner. Agents that function as glutamatergic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor agonists, alpha2-adrenergic receptor antagonists (such as yohimbine), neurotrophic factors (brain derived neurotrophic factor or BDNF) and histone deacetylase inhibitors (valproate and sodium butyrate) also improve fear extinction in animals. However, some have anxiogenic effects and their contextual and temporal effects need to be more reliably demonstrated. Various cognitive enhancers produce changes in cortico-amygdala synaptic plasticity through multiple mechanisms and these neural changes enhance fear extinction. We need to better define the changes in neural plasticity produced by these agents in order to develop more effective compounds. In the clinical

  3. Effects of Exercise and Environmental Complexity on Deficits in Trace and Contextual Fear Conditioning Produced by Neonatal Alcohol Exposure in Rats

    OpenAIRE

    Schreiber, W.B.; St. Cyr, S.A.; Jablonski, S A; Hunt, P S; Klintsova, A.Y.; Stanton, M.E.

    2012-01-01

    In rodents, voluntary exercise and environmental complexity increases hippocampal neurogenesis and reverses spatial learning and long-term potentiation deficits in animals prenatally exposed to alcohol. The present experiment extended these findings to neonatal alcohol exposure and to delay, trace, and contextual fear conditioning. Rats were administered either 5.25 g/kg/day alcohol via gastric intubation or received sham-intubations (SI) between Postnatal Day (PD) 4 and 9 followed by either ...

  4. Overexpression of Homer1a in the basal and lateral amygdala impairs fear conditioning and induces an autism-like social impairment

    OpenAIRE

    Banerjee, Anwesha; Luong, Jonathan A.; Ho, Anthony,; Saib, Aeshah O.; Ploski, Jonathan E.

    2016-01-01

    Background Autism spectrum disorders (ASDs) represent a heterogeneous group of disorders with a wide range of behavioral impairments including social and communication deficits. Apart from these core symptoms, a significant number of ASD individuals display higher levels of anxiety, and some studies indicate that a subset of ASD individuals have a reduced ability to be fear conditioned. Deciphering the molecular basis of ASD has been considerably challenging and it currently remains poorly un...

  5. Neuroleptic Drugs Revert the Contextual Fear Conditioning Deficit Presented by Spontaneously Hypertensive Rats: A Potential Animal Model of Emotional Context Processing in Schizophrenia?

    OpenAIRE

    Calzavara, Mariana Bendlin; Medrano, Wladimir Agostini; Levin, Raquel; Kameda, Sonia Regina; Andersen, Monica Levy; Tufik, Sergio; Silva, Regina Helena; Frussa-Filho, Roberto; Abílio, Vanessa Costhek

    2008-01-01

    Schizophrenia, bipolar disorder, and attention deficit/hyperactivity disorder (ADHD) present abnormalities in emotion processing. A previous study showed that the spontaneously hypertensive rats (SHR), a putative animal model of ADHD, present reduced contextual fear conditioning (CFC). The aim of the present study was to characterize the deficit in CFC presented by SHR. Adult male normotensive Wistar rats and SHR were submitted to the CFC task. Sensitivity of the animals to the shock and the ...

  6. Eyeblink Classical Conditioning and Post-Traumatic Stress Disorder – A Model Systems Approach

    OpenAIRE

    Schreurs, Bernard G.; Burhans, Lauren B.

    2015-01-01

    Not everyone exposed to trauma suffers flashbacks, bad dreams, numbing, fear, anxiety, sleeplessness, hyper-vigilance, hyperarousal, or an inability to cope, but those who do may suffer from post-traumatic stress disorder (PTSD). PTSD is a major physical and mental health problem for military personnel and civilians exposed to trauma. There is still debate about the incidence and prevalence of PTSD especially among the military, but for those who are diagnosed, behavioral therapy and drug tre...

  7. Classical conditioning mechanisms can differentiate between seeing and doing in rats.

    Science.gov (United States)

    Kutlu, Munir G; Schmajuk, Nestor A

    2012-01-01

    We show that the attentional-associative SLG model of classical conditioning, based on the 1996 research of Schmajuk, Lam, and Gray, correctly describes experimental results regarded as evidence of causal learning in rats: (a) interventions attenuate responding following common-cause training but do not interfere on subsequent responding during observation, and (b) interventions do not affect responding after direct-cause training or (c) causal-chain training. According to the model, responding to the weakly attended test stimulus is strongly inhibited by the intervention in the common-cause case. Instead, in the direct-cause and causal-chain cases, the strongly attended test stimulus becomes inhibitory, thereby overshadowing the inhibitory effect of interventions. Most importantly, the model predicted that with relatively few test trials (a) the 2008 results of Experiment 3 by Leising, Wong, Waldmann, and Blaisdell should be similar to those of Dwyer, Starns, and Honey's 2009 Experiment 1, showing that interventions equally affect responding after common-cause and direct-cause training; and (b) the 2006 results of Experiment 2a by Blaisdell, Sawa, Leising, and Waldmann should be similar to those of Dwyer, Starns, and Honey's 2009 Experiment 2, showing that interventions equally affect responding after common-cause and causal-chain training. When those data were made available to us, we confirmed those predictions. In agreement with the SLG associative model, but not with causal model theory, this evidence supports the notion that the attenuation of responding by interventions only following common-cause training is the consequence of well-known learning processes-latent inhibition, sensory preconditioning, conditioned inhibition, protection from extinction, and overshadowing. PMID:22229589

  8. Repeated elicitation of the acoustic startle reflex leads to sensitisation in subsequent avoidance behaviour and induces fear conditioning

    Directory of Open Access Journals (Sweden)

    Janik Vincent M

    2011-04-01

    Full Text Available Abstract Background Autonomous reflexes enable animals to respond quickly to potential threats, prevent injury and mediate fight or flight responses. Intense acoustic stimuli with sudden onsets elicit a startle reflex while stimuli of similar intensity but with longer rise times only cause a cardiac defence response. In laboratory settings, habituation appears to affect all of these reflexes so that the response amplitude generally decreases with repeated exposure to the stimulus. The startle reflex has become a model system for the study of the neural basis of simple learning processes and emotional processing and is often used as a diagnostic tool in medical applications. However, previous studies did not allow animals to avoid the stimulus and the evolutionary function and long-term behavioural consequences of repeated startling remain speculative. In this study we investigate the follow-up behaviour associated with the startle reflex in wild-captured animals using an experimental setup that allows individuals to exhibit avoidance behaviour. Results We present evidence that repeated elicitation of the acoustic startle reflex leads to rapid and pronounced sensitisation of sustained spatial avoidance behaviour in grey seals (Halichoerus grypus. Animals developed rapid flight responses, left the exposure pool and showed clear signs of fear conditioning. Once sensitised, seals even avoided a known food source that was close to the sound source. In contrast, animals exposed to non-startling (long rise time stimuli of the same maximum sound pressure habituated and flight responses waned or were absent from the beginning. The startle threshold of grey seals expressed in units of sensation levels was comparable to thresholds reported for other mammals (93 dB. Conclusions Our results demonstrate that the acoustic startle reflex plays a crucial role in mediating flight responses and strongly influences the motivational state of an animal beyond a short

  9. Effects of Storage Time and Condition on Mineral Contents of Grape Pekmez Produced by Vacuum and Classical Methods

    Directory of Open Access Journals (Sweden)

    B. Kayisoglu

    2006-01-01

    Full Text Available This study was conducted to investigate the effect of storage period and conditions on chemical properties of boiled grape juice (pekmez produced from the grape variety of Kınalı Yapıncak using classical and vacuum methods. Pekmez samples were stored in 250 cc volumed jars. Products obtained using two different production methods were stored for 10 months in room conditions and at +4 ºC temperature. Starting from the beginning of the storage, mineral analyses were repeated in every two months. Average copper, manganese, phosphorus, and sodium contents in pekmez samples produced by vacuum method were higher than by classical method at the end of storage period. But, calcium content in pekmez samples produced by classical method was higher than that of the other. Zinc, iron, and potassium contents in either vacuum method or classical method were not significantly different. In conclusion; in general, mineral contents were better in pekmez produced by vacuum method than classical method. Phosphor, sodium, potassium, calcium, copper, zinc and manganese contents were affected significantly by storage period, but iron was not. In addition, storage condition did not affect sodium, zinc and iron contents.

  10. Stress before Puberty Exerts a Sex- and Age-Related Impact on Auditory and Contextual Fear Conditioning in the Rat

    OpenAIRE

    2007-01-01

    Adolescence is a period of major physical, hormonal, and psychological changes. It is also characterized by a significant increase in the incidence of psychopathologies and this increase is gender-specific. Stress during adolescence is associated with the development of psychiatric disorders later in life. In this study, we evaluated the impact of psychogenic stress (exposure to predator odor followed by placement on an elevated platform) experienced before puberty (days 28–30) on fear m...

  11. Stress before Puberty Exerts a Sex- and Age-Related Impact on Auditory and Contextual Fear Conditioning in the Rat

    OpenAIRE

    Maria Toledo-Rodriguez; Carmen Sandi

    2007-01-01

    Adolescence is a period of major physical, hormonal, and psychological changes. It is also characterized by a significant increase in the incidence of psychopathologies and this increase is gender-specific. Stress during adolescence is associated with the development of psychiatric disorders later in life. In this study, we evaluated the impact of psychogenic stress (exposure to predator odor followed by placement on an elevated platform) experienced before puberty (days 28–30) on fear memori...

  12. Hippocampal Non-Theta-Contingent Eyeblink Classical Conditioning: A Model System for Neurobiological Dysfunction.

    Science.gov (United States)

    Cicchese, Joseph J; Berry, Stephen D

    2016-01-01

    Typical information processing is thought to depend on the integrity of neurobiological oscillations that may underlie coordination and timing of cells and assemblies within and between structures. The 3-7 Hz bandwidth of hippocampal theta rhythm is associated with cognitive processes essential to learning and depends on the integrity of cholinergic, GABAergic, and glutamatergic forebrain systems. Since several significant psychiatric disorders appear to result from dysfunction of medial temporal lobe (MTL) neurochemical systems, preclinical studies on animal models may be an important step in defining and treating such syndromes. Many studies have shown that the amount of hippocampal theta in the rabbit strongly predicts the acquisition rate of classical eyeblink conditioning and that impairment of this system substantially slows the rate of learning and attainment of asymptotic performance. Our lab has developed a brain-computer interface that makes eyeblink training trials contingent upon the explicit presence or absence of hippocampal theta. The behavioral benefit of theta-contingent training has been demonstrated in both delay and trace forms of the paradigm with a two- to fourfold increase in learning speed over non-theta states. The non-theta behavioral impairment is accompanied by disruption of the amplitude and synchrony of hippocampal local field potentials, multiple-unit excitation, and single-unit response patterns dependent on theta state. Our findings indicate a significant electrophysiological and behavioral impact of the pretrial state of the hippocampus that suggests an important role for this MTL system in associative learning and a significant deleterious impact in the absence of theta. Here, we focus on the impairments in the non-theta state, integrate them into current models of psychiatric disorders, and suggest how improvement in our understanding of neurobiological oscillations is critical for theories and treatment of psychiatric

  13. Pharmacological intervention of conditioned fear and its extinction%条件性恐惧消退的药理学干预

    Institute of Scientific and Technical Information of China (English)

    黄任之; 李则宣; 陈欢; 黄月胜; 丁立平

    2012-01-01

    Conditioned fear and its abnormal extinction are involved in the psychopathology of anxiety disorders, such as posttraumatic stress disorder (PTSD). Cognitive enhancing agents have been demonstrated to alter fear extinction in many animal research literatures. The present review has examined the pharmacological role of gamma-aminobutyric acid (GABA), glutamatergic, cholinergic, adrenergic, dopaminergic, and cannabinoid as well as compounds able to alter the epigenetic and neurotrophic mechanism in fear extinction, highlighting great hope for the future treatment of anxiety disorders with new agents based on the fear extinction.%条件性恐惧记忆及其消退的异常参与焦虑障碍如创伤后应激障碍的精神病理机制.大量的动物研究已经展示了药理学手段增强条件性恐惧消退的可能性;对此,本文从作用于gamma-氨基丁酸能、谷氨酸能、胆碱能、肾上腺素能、多巴胺能和大麻素能以及从改变表观遗传学和神经营养机制的药理学方面进行综述,表明临床上开发和使用药理学干预来增强基于消退原理的暴露疗法治疗焦虑障碍可能具有远大的前景.

  14. Are fear memories erasable? –reconsolidation of learned fear with fear relevant and fear-irrelevant stimuli

    Directory of Open Access Journals (Sweden)

    Armita Golkar

    2012-11-01

    Full Text Available Recent advances in the field of fear learning have demonstrated that a single reminder exposure prior to extinction training can prevent the return of extinguished fear by disrupting the process of reconsolidation. These findings have however proven hard to replicate in humans. Given the significant implications of preventing the return of fear, the purpose of the present study was to further study the prerequisites for the putative effects of disrupting reconsolidation. In two experiments, we assessed whether extinction training initiated within the reconsolidation time window could abolish the return of fear using fear-relevant (experiment 1 or fear-irrelevant (experiment 2 conditioned stimuli (CS. In both experiments, participants went through conditioning, extinction and reinstatement testing on three consecutive days, with one of two reinforced CS being reactivated 10 minutes prior to extinction. We found that a single reminder exposure prior to extinction training did not prevent the return of extinguished fear responding using either fear-relevant or fear-irrelevant CSs. Our findings point to the need to further study the specific parameters that enable disruption of reconsolidation.

  15. Effects of Paradigm and Inter-Stimulus Interval on Age Differences in Eyeblink Classical Conditioning in Rabbits

    Science.gov (United States)

    Woodruff-Pak, Diana S.; Seta, Susan E.; Roker, LaToya A.; Lehr, Melissa A.

    2007-01-01

    The aim of this study was to examine parameters affecting age differences in eyeblink classical conditioning in a large sample of young and middle-aged rabbits. A total of 122 rabbits of mean ages of 4 or 26 mo were tested at inter-stimulus intervals (ISIs) of 600 or 750 msec in the delay or trace paradigms. Paradigm affected both age groups…

  16. 条件性恐惧记忆消退返回的性别差异%Sex Differences in Extinction Return of Conditioned Fear Memory

    Institute of Scientific and Technical Information of China (English)

    孙楠; 魏艺铭; 李倩; 郑希付

    2012-01-01

    Posttraumatic stress disorder is a kind of anxiety disorder which developed after severe trauma. Conditioned fear model is the most emblematical model of posttraumatic stress disorder. At the present time, the most effective therapy is the exposure therapy which uses extinction training to repress the conditioned fear memory. However, some of the PTSD patients were having relapses after the exposure therapy, these relapses were later named as the extinction return.An experiment was designed to research for sex differences in the extinction return of conditioned fear memory. Forty normal students participated in the experiment, including 20 females and 20 males. Before the actual experiment, the participants had to attend the extinction training session; the participants were trained to consciously establish and extinguish the connection between neutral stimulus and repugnant stimulus. The experiment consisted of pre-exposure, acquisition, extinction, and test phases. The pre-exposure phase required the participants to understand the procedure. In the acquisition phase, the participants would acquire the conditioned fear response via the connection of the neutral stimulus and the repugnant stimulus. In the extinction, the neutral stimulus would be presented alone without the repugnant stimulus. Four hours later, test phase was to examine whether the extinction return would be found, and whether males or females performed differently on the acquisition and extinction of conditioned fear memory.The results were as following: (1) The participants were observed to have obvious extinction return overall when they were tested after 4 hours later during the extinction phase. (2)The extinction return in females was much more significant than in males. (3)The females tended to acquire the conditioned fear memory more effectively and extinguish more slowly than males. But the difference is not significant.The results of this study suggested that the extinction return was a

  17. Use of the ABA Fear Renewal Paradigm to Assess the Effects of Extinction with Co-Present Fear Inhibitors or Excitors: Implications for Theories of Extinction and for Treating Human Fears and Phobias

    Science.gov (United States)

    Thomas, Brian L.; Ayres, John J. B.

    2004-01-01

    In four experiments using albino rats in an ABA fear renewal paradigm, we studied conditioned fear in the A test context following extinction in Context B. Conditioned suppression of operant responding was the index of fear. In Experiments 1-3, we found that extinguishing a feared cue in compound with a putative conditioned inhibitor of fear led…

  18. Nicotine ameliorates NMDA receptor antagonist-induced deficits in contextual fear conditioning through high-affinity nicotinic acetylcholine receptors in the hippocampus.

    Science.gov (United States)

    André, Jessica M; Leach, Prescott T; Gould, Thomas J

    2011-03-01

    NMDA glutamate receptors (NMDARs) and nicotinic acetylcholine receptors (nAChRs) are both involved in learning and synaptic plasticity. Increasing evidence suggests processes mediated by these receptors may interact to modulate learning; however, little is known about the neural substrates involved in these interactive processes. The present studies investigated the effects of nicotine on MK-801 hydrogen maleate (MK-801) and DL-2-Amino-5-phosphonovaleric acid (APV)-induced disruption of contextual fear conditioning in male C57BL/6J mice, using direct drug infusion and selective nAChR antagonists to define the brain regions and the nAChR subtypes involved. Mice treated with MK-801 showed a deficit in contextual fear conditioning that was ameliorated by nicotine. Direct drug infusion demonstrated that the NMDAR antagonists disrupted hippocampal function and that nicotine acted in the dorsal hippocampus to ameliorate the deficit in learning. The high-affinity nAChR antagonist Dihydro-β-erythroidine hydrobromide (DhβE) blocked the effects of nicotine on MK-801-induced deficits while the α7 nAChR antagonist methyllycaconitine citrate salt hydrate (MLA) did not. These results suggest that NMDARs and nAChRs may mediate similar hippocampal processes involved in contextual fear conditioning. Furthermore, these results may have implications for developing effective therapeutics for the cognitive deficits associated with schizophrenia because a large subset of patients with schizophrenia exhibit cognitive deficits that may be related to NMDAR dysfunction and smoke at much higher rates than the healthy population, which may be an attempt to ameliorate cognitive deficits. PMID:21167848

  19. Accumulation of anthropogenic radionuclides in crops in conditions of water stream and classical hydroponics

    Energy Technology Data Exchange (ETDEWEB)

    Mayrapetyan, Khachatur; Hovsepyan, Albert; Daryadar, Mahsa; Alexanyan, Julietta; Tovmasyan, Anahit; Ghalachyan, Laura; Tadevosyan, Anna; Mayrapetyan, Stepan [Institute of Hydroponics Problems, NAS, Noragyugh 108, 0082, Yerevan (Armenia)

    2014-07-01

    Natural and artificial radionuclides (RN) dangerous for health are emitted into ecosystems because of human anthropogenic activities in the field of nuclear energetics. Biologically artificial RN {sup 90}Sr(T{sub 1/2}=28,6 years) and {sup 137}Cs (T{sub 1/2}=30,1 years)are very dangerous. Therefore obtaining radio-ecologically safe raw material of high quality is a very urgent problem now. Taking into account the above mentioned, in order to obtain ecologically safe raw material we carried out comparative radiochemical investigations on essential oil and medicinal plants peppermint(Mentha piperita L.) and sweet basil (Ocimum basilicum L.) grown in new water-stream (continuous, gully, cylindrical) and classical hydroponics, with the aim of revealing accumulation peculiarities of {sup 90}Sr and {sup 137}Cs. The results of experiments have shown that in classical hydroponics peppermint and sweet basil exceeded the same indices of water-stream hydroponics with {sup 90}Sr and {sup 137}Cs content 1,1-1,2; 1,2-1,3 and 1,5-1,8; 1,4-1,8 times, respectively. Moreover, sweet basil exceeded peppermint in water-stream hydroponics {sup 90}Sr 1,3-1,6; {sup 137}Cs 1,2-1,4 times and in classical hydroponics {sup 90}Sr 1,6; {sup 137}Cs 1,2 times. The content of controlled artificial RN in raw material did not exceed the allowed concentration limit (ACL). New water-stream hydroponics system worked out in Institute of Hydroponics Problems is a radio-ecologically more profitable method for producing raw material than classical hydroponics. At the same time water-stream hydroponics system in comparison with classical hydroponics promoted productivity (dry raw material) increase of peppermint and sweet basil 1,1-1,4 times. (authors)

  20. Immunization against social fear learning.

    Science.gov (United States)

    Golkar, Armita; Olsson, Andreas

    2016-06-01

    Social fear learning offers an efficient way to transmit information about potential threats; little is known, however, about the learning processes that counteract the social transmission of fear. In three separate experiments, we found that safety information transmitted from another individual (i.e., demonstrator) during preexposure prevented subsequent observational fear learning (Experiments 1-3), and this effect was maintained in a new context involving direct threat confrontation (Experiment 3). This protection from observational fear learning was specific to conditions in which information about both safety and danger was transmitted from the same demonstrator (Experiments 2-3) and was unaffected by increasing the number of the safety demonstrators (Experiment 3). Collectively, these findings demonstrate that observational preexposure can limit social transmission of fear. Future research is needed to better understand the conditions under which such effects generalize across individual demonstrators. (PsycINFO Database Record PMID:27077756

  1. Fear at the Great Wall

    Institute of Scientific and Technical Information of China (English)

    CHARLOTTE; SPIRES

    2011-01-01

    "i’m not going on anything that takes me more than two feet off the ground," Grace was saying.This was classic Grace: She has a morbid fear of—well, everything actually,but in this particular case it was her phobia of heights, heights and cable cars combined specifically.

  2. Fear at the Great Wall

    Institute of Scientific and Technical Information of China (English)

    CHARLOTTE SPIRES

    2011-01-01

    “I’m not going on anything that takes me more than two feet off the ground," Grace was saying.This was classic Grace:She has a morbid fear of-well,everything actually,but in this particular case it was her phobia of heights,heights and cable cars combined specifically.

  3. Arousal and Associative Processes in Reinstatement of Fear

    OpenAIRE

    Glenn, Daniel Erik

    2014-01-01

    This dissertation is a two-paper investigation of the basic associative and arousal-based processes involved in reinstatement of conditional fear. Clarifying the factors involved in reinstatement of fear--a behavioral phenomenon in which the experience of an aversive event following fear extinction produces a return of fear--provides a better understanding of the factors that contribute to the waxing and waning of untreated fear and the return of fear following exposure treatment. Shedding li...

  4. Placing prediction into the fear circuit

    OpenAIRE

    McNally, Gavan P.; Johansen, Joshua P.; Blair, Hugh T.

    2011-01-01

    Pavlovian fear conditioning depends on synaptic plasticity at amygdala neurons. Here we review recent electrophysiological, molecular, and behavioral evidence suggesting the existence of a distributed neural circuitry regulating amygdala synaptic plasticity during fear learning. This circuitry, which involves projections from the midbrain periaqueductal gray (PAG) region, can be linked to prediction error and expectation modulation of fear learning as described by associative and computationa...

  5. Learning in a simple biological system: a pilot study of classical conditioning of human macrophages in vitro

    Directory of Open Access Journals (Sweden)

    Nilsonne Gustav

    2011-11-01

    Full Text Available Abstract Recent advances in cell biology and gene regulation suggest mechanisms whereby associative learning could be performed by single cells. Therefore, we explored a model of classical conditioning in human macrophages in vitro. In macrophage cultures, bacterial lipopolysaccharide (LPS; unconditioned stimulus was paired once with streptomycin (conditioned stimulus. Secretion of interleukin-6 (IL-6 was used as response measure. At evocation, conditioning was not observed. Levels of IL-6 were higher only in those cultures that had been exposed to LPS in the learning phase (p's However, habituation was evident, with a 62% loss of the IL-6 response after three LPS presentations (p

  6. Hippocampal Arc (Arg3.1) expression is induced by memory recall and required for memory reconsolidation in trace fear conditioning.

    Science.gov (United States)

    Chia, Chester; Otto, Tim

    2013-11-01

    Mounting evidence suggests that long-lasting, protein synthesis-dependent changes in synaptic strength accompany both the initial acquisition and subsequent recall of specific memories. Within brain areas thought to be important for learning and memory, including the hippocampus, learning-related plasticity is likely mediated in part by NMDA receptor activation and experience-dependent changes in gene expression. In the present study, we examined the role of activity-regulated cytoskeletal-associated protein (Arc/Arg3.1) expression in the acquisition, recall, and reconsolidation of memory in a trace fear conditioning paradigm. First, we show that the expression of Arc protein in ventral hippocampus (VH) is dramatically enhanced by memory recall 24h after the acquisition of trace fear conditioning, and that both memory recall and the associated recall-induced enhancement of Arc expression are blocked by pre-training administration of 2-amino-5-phosphonovaleric acid (APV). Next, we show that while infusion of Arc antisense oligodeoxynucleotides (ODNs) into VH prior to testing had little effect on memory recall, it significantly reduced both Arc protein expression and freezing behavior during subsequent testing sessions. Collectively, these results suggest that Arc/Arg3.1 protein plays an important functional role in both the initial acquisition of hippocampal-dependent memory and the reconsolidation of these memories after recall. PMID:23872190

  7. Blocking glucocorticoid receptors at adolescent age prevents enhanced freezing between repeated cue-exposures after conditioned fear in adult mice raised under chronic early life stress.

    Science.gov (United States)

    Arp, J Marit; Ter Horst, Judith P; Loi, Manila; den Blaauwen, Jan; Bangert, Eline; Fernández, Guillén; Joëls, Marian; Oitzl, Melly S; Krugers, Harm J

    2016-09-01

    Early life adversity can have long-lasting impact on learning and memory processes and increase the risk to develop stress-related psychopathologies later in life. In this study we investigated (i) how chronic early life stress (ELS) - elicited by limited nesting and bedding material from postnatal day 2 to 9 - affects conditioned fear in adult mice and (ii) whether these effects can be prevented by blocking glucocorticoid receptors (GRs) at adolescent age. In adult male and female mice, ELS did not affect freezing behavior to the first tone 24h after training in an auditory fear-conditioning paradigm. Exposure to repeated tones 24h after training also resulted in comparable freezing behavior in ELS and control mice, both in males and females. However, male (but not female) ELS compared to control mice showed significantly more freezing behavior between the tone-exposures, i.e. during the cue-off periods. Intraperitoneal administration of the GR antagonist RU38486 during adolescence (on postnatal days 28-30) fully prevented enhanced freezing behavior during the cue-off period in adult ELS males. Western blot analysis revealed no effects of ELS on hippocampal expression of glucocorticoid receptors, neither at postnatal day 28 nor at adult age, when mice were behaviorally tested. We conclude that ELS enhances freezing behavior in adult mice in a potentially safe context after cue-exposure, which can be normalized by brief blockade of glucocorticoid receptors during the critical developmental window of adolescence. PMID:27246249

  8. Food fears

    International Nuclear Information System (INIS)

    Radurisation can give a new lease of shelf life to food and cut down contamination, but it is bound to cause problems - even among comparatively tame South African consumers. In this article the facts about radurization are discussed: the labelling of irradiated products, the problem of making a bad product good by using irradiation, consumer pressure, attitudes, fears and resistance. The economics of radurised foodstuffs are also discussed

  9. Sex- and dose-dependent effects of calcium ion irradiation on behavioral performance of B6D2F1 mice during contextual fear conditioning training

    Science.gov (United States)

    Raber, Jacob; Weber, Sydney J.; Kronenberg, Amy; Turker, Mitchell S.

    2016-06-01

    The space radiation environment includes energetic charged particles that may impact behavioral and cognitive performance. The relationship between the dose and the ionization density of the various types of charged particles (expressed as linear energy transfer or LET), and cognitive performance is complex. In our earlier work, whole body exposure to 28Si ions (263 MeV/n, LET = 78keV / μ m ; 1.6 Gy) affected contextual fear memory in C57BL/6J × DBA2/J F1 (B6D2F1) mice three months following irradiation but this was not the case following exposure to 48Ti ions (1 GeV/n, LET = 107keV / μ m ; 0.2 or 0.4 Gy). As an increased understanding of the impact of charged particle exposures is critical for assessment of risk to the CNS of astronauts during and following missions, in this study we used 40Ca ion beams (942 MeV/n, LET = 90keV / μm) to determine the behavioral and cognitive effects for the LET region between that of Si ions and Ti ions. 40Ca ion exposure reduced baseline activity in a novel environment in a dose-dependent manner, which suggests reduced motivation to explore and/or a diminished level of curiosity in a novel environment. In addition, exposure to 40Ca ions had sex-dependent effects on response to shock. 40Ca ion irradiation reduced the response to shock in female, but not male, mice. In contrast, 40Ca ion irradiation did not affect fear learning, memory, or extinction of fear memory for either gender at the doses employed in this study. Thus 40Ca ion irradiation affected behavioral, but not cognitive, performance. The effects of 40Ca ion irradiation on behavioral performance are relevant, as a combination of novelty and aversive environmental stimuli is pertinent to conditions experienced by astronauts during and following space missions.

  10. What ethologically based models have taught us about the neural systems underlying fear and anxiety

    Directory of Open Access Journals (Sweden)

    N.S. Canteras

    2012-04-01

    Full Text Available Classical Pavlovian fear conditioning to painful stimuli has provided the generally accepted view of a core system centered in the central amygdala to organize fear responses. Ethologically based models using other sources of threat likely to be expected in a natural environment, such as predators or aggressive dominant conspecifics, have challenged this concept of a unitary core circuit for fear processing. We discuss here what the ethologically based models have told us about the neural systems organizing fear responses. We explored the concept that parallel paths process different classes of threats, and that these different paths influence distinct regions in the periaqueductal gray - a critical element for the organization of all kinds of fear responses. Despite this parallel processing of different kinds of threats, we have discussed an interesting emerging view that common cortical-hippocampal-amygdalar paths seem to be engaged in fear conditioning to painful stimuli, to predators and, perhaps, to aggressive dominant conspecifics as well. Overall, the aim of this review is to bring into focus a more global and comprehensive view of the systems organizing fear responses.

  11. Mice lacking Ras-GRF1 show contextual fear conditioning but not spatial memory impairments: convergent evidence from two independently generated mouse mutant lines

    Directory of Open Access Journals (Sweden)

    Raffaele ed'Isa

    2011-12-01

    Full Text Available Ras-GRF1 is a neuronal specific guanine exchange factor that, once activated by both ionotropic and metabotropic neurotransmitter receptors, can stimulate Ras proteins, leading to long-term phosphorylation of downstream signaling. The two available reports on the behavior of two independently generated Ras-GRF1 deficient mouse lines provide contrasting evidence on the role of Ras-GRF1 in spatial memory and contextual fear conditioning. These discrepancies may be due to the distinct alterations introduced in the mouse genome by gene targeting in the two lines that could differentially affect expression of nearby genes located in the imprinted region containing the Ras-grf1 locus. In order to determine the real contribution of Ras-GRF1 to spatial memory we compared in Morris Water Maze learning the Brambilla’s mice with a third mouse line (GENA53 in which a nonsense mutation was introduced in the Ras-GRF1 coding region without additional changes in the genome and we found that memory in this task is normal. Also, we measured both contextual and cued fear conditioning, which were previously reported to be affected in the Brambilla’s mice, and we confirmed that contextual learning but not cued conditioning is impaired in both mouse lines. In addition, we also tested both lines for the first time in conditioned place aversion in the Intellicage, an ecological and remotely controlled behavioral test, and we observed normal learning. Finally, based on previous reports of other mutant lines suggesting that Ras-GRF1 may control body weight, we also measured this non-cognitive phenotype and we confirmed that both Ras-GRF1 deficient mutants are smaller than their control littermates. In conclusion, we demonstrate that Ras-GRF1 has no unique role in spatial memory while its function in contextual fear conditioning is likely to be due not only to its involvement in amygdalar functions but possibly to some distinct hippocampal connections specific to

  12. Enhanced discriminative fear learning of phobia-irrelevant stimuli in spider-fearful individuals

    Directory of Open Access Journals (Sweden)

    Carina eMosig

    2014-10-01

    Full Text Available Avoidance is considered as a central hallmark of all anxiety disorders. The acquisition and expression of avoidance which leads to the maintenance and exacerbation of pathological fear is closely linked to Pavlovian and operant conditioning processes. Changes in conditionability might represent a key feature of all anxiety disorders but the exact nature of these alterations might vary across different disorders. To date, no information is available on specific changes in conditionability for disorder-irrelevant stimuli in specific phobia (SP. The first aim of this study was to investigate changes in fear acquisition and extinction in spider-fearful individuals as compared to non-fearful participants by using the de novo fear conditioning paradigm. Secondly, we aimed to determine whether differences in the magnitude of context-dependent fear retrieval exist between spider-fearful and non-fearful individuals. Our findings point to an enhanced fear discrimination in spider-fearful individuals as compared to non-fearful individuals at both the physiological and subjective level. The enhanced fear discrimination in spider-fearful individuals was neither mediated by increased state anxiety, depression, nor stress tension. Spider-fearful individuals displayed no changes in extinction learning and/or fear retrieval. Surprisingly, we found no evidence for context-dependent modulation of fear retrieval in either group. Here we provide first evidence that spider-fearful individuals show an enhanced discriminative fear learning of phobia-irrelevant (de novo stimuli. Our findings provide novel insights into the role of fear acquisition and expression for the development and maintenance of maladaptive responses in the course of SP.

  13. Cdk5 Kinase Activity, Caspase-3 Expression and Synaptic Structural Plasticity in Infra-limbic Cortex of Rats with Conditioned Fear%条件性恐惧大鼠边缘下区Cdk5激酶活性、caspase-3表达以及突触结构的变化

    Institute of Scientific and Technical Information of China (English)

    李培培; 张丽丽; 韦美; 李敏

    2011-01-01

    Classical fear conditioning is a behavioral paradigm that is widely used to study the neuronal mechanisms of post-traumatic stress disorder. Previous studies have clearly identified the medial prefrontal cortex as a key brain area for fear memory traces, but the molecules involving are poorly understood. Recently, the neuronal cyclin dependent kinase 5 (Cdk5) has been implicated in both functional and structural plasticity through affecting ion channel conductance, dendritic spine formation. protein expressions and transcriptions in the postsynaptic neurons. Importantly, dysregulation of Cdk5 has been linked to cell apoptosis, which involves perturbation in synaptic function. How the kinase activity, expression of caspase-3 and synaptic structure have changed in infra-limbic cortex (IL) of conditioned fear? The present study is aimed to answer this question by two experiments.Male adult SD rats were randomly divided into fear group and naive group. Conditioned fear model of rats was established by tone paired foot shock. At the 2nd, 4th and 8th days after fear conditioning, the Cdk5 activity,and expressions of P35 or P25 and caspase-3 in IL area were studied by immunoprecipitation and kinase assay,Western blotting and immunnohistochemical assay. Then the change of synaptic structure at the 8th and 22nd days after conditioned fear was observed with electron microscopy. The results of our experiment 1 showed that Cdk5 activity and expressions of P25 and caspase-3 were all higher in fear group than naive group. In experiment 2, the postsynaptic density (PSD) was thinner in fear group than naive group at the 8th and 22nd days after fear conditioning, but the numerical densities of IL synapse was decreased in fear group at the 22nd day after fear conditioning.Our date suggested that at 8th days after conditioned fear established, the expression of P25 and Cdk5 activity in fear group were higher than naive group, which may lead to the change of synaptic structural

  14. Adolescent and adult rats differ in the amnesic effects of acute ethanol in two hippocampus-dependent tasks: Trace and contextual fear conditioning.

    Science.gov (United States)

    Hunt, Pamela S; Barnet, Robert C

    2016-02-01

    Experience-produced deficits in trace conditioning and context conditioning have been useful tools for examining the role of the hippocampus in learning. It has also been suggested that learning in these tasks is especially vulnerable to neurotoxic effects of alcohol during key developmental periods such as adolescence. In five experiments we systematically examined the presence and source of age-dependent vulnerability to the memory-disrupting effects of acute ethanol in trace conditioning and contextual fear conditioning. In Experiment 1a pre-training ethanol disrupted trace conditioning more strongly in adolescent (postnatal day, PD30-35) than adult rats (PD65-75). In Experiment 1b when pre-training ethanol was accompanied by pre-test ethanol no deficit in trace conditioning was observed in adolescents, suggesting that state-dependent retrieval failure mediated ethanol's disruption of trace conditioning at this age. Experiment 2a and b examined the effect of ethanol pretreatment on context conditioning. Here, adult but not adolescent rats were impaired in conditioned freezing to context cues. Experiment 2c explored state-dependency of this effect. Pre-training ethanol continued to disrupt context conditioning in adults even when ethanol was also administered prior to test. Collectively these findings reveal clear age-dependent and task-dependent vulnerabilities in ethanol's disruptive effects on hippocampus-dependent memory. Adolescents were more disrupted by ethanol in trace conditioning than adults, and adults were more disrupted by ethanol in context conditioning than adolescents. We suggest that adolescents may be more susceptible to changes in internal state (state-dependent retrieval failure) than adults and that ethanol disrupted performance in trace and context conditioning through different mechanisms. Relevance of these findings to theories of hippocampus function is discussed. PMID:26192910

  15. Neural correlates of the mother-to-infant social transmission of fear.

    Science.gov (United States)

    Chang, Da-Jeong; Debiec, Jacek

    2016-06-01

    Although clinical and basic studies show that parental trauma, fear, and anxiety may be transmitted to offspring, the neurobiology of this transmission is still not well understood. We recently demonstrated in an animal model that infant rats acquire threat responses to a distinct cue when a mother expresses fear to this cue in their presence. This ability to acquire maternal fear through social learning is present at birth and, as we previously reported, depends on the pup's amygdala. However, the remaining neural mechanisms underlying social fear learning (SFL) in infancy remain elusive. Here, by using [(14) C]2-deoxyglucose autoradiography, we show that the mother-to-infant transmission of fear in preweaning rats is associated with a significant increase of activity in the subregions of the lateral septum, nucleus accumbens, bed nucleus of stria terminalis, retrosplenial cortex, paraventricular nucleus of the thalamus, mediodorsal and intralaminar thalamic nuclei, medial and the lateral preoptic nuclei of the hypothalamus, and the lateral periaqueductal gray. In contrast to studies of adult SFL demonstrating the role of the anterior cingulate cortex and possibly the insular cortex or research of infant classical fear conditioning showing the role of the posterior piriform cortex, no changes of activation in these areas were observed. Our results indicate that the pup's exposure to maternal fear activates a number of areas involved in processing threat, stress, or pain. This pattern of activation suggests a unique set of neural mechanisms underlying SFL in the developing brain. © 2016 Wiley Periodicals, Inc. PMID:27091313

  16. [AMYGDALA: NEUROANATOMY AND NEUROPHYSIOLOGY OF FEAR].

    Science.gov (United States)

    Tsvetkov, E A; Krasnoshchekova, E I; Vesselkin, N P; Kharazova, A D

    2015-01-01

    This work describes neuroanatomical and neurophysiological mechanisms of Pavlovian fear conditioning, focusing on contributions of the amygdala, a subcortical nuclear group, to control of conditioned fear responses. The mechanisms of synaptic plasticity at projections to the amygdala and within amygdala were shown to mediate the formation and retention of fear memory. This work reviews current data on anatomical organization of the amygdala, as well as its afferent and efferent projections, in respect to the role of the amygdala in auditory fear conditioning during which acoustic signals serve as the conditioned stimulus. PMID:26983275

  17. Sensitization to apomorphine in pigeons : unaffected by latent inhibition but still due to classical conditioning

    OpenAIRE

    Wynne, Brigitte; Delius, Juan

    1995-01-01

    When administered apomorphine, pigeons exhibit protracted bouts of pecking behavior. This response is subject to sensitization, as it initially increases with repeated drug injections. The hypothesis is examined that the sensitization is due to a Pavlovian conditioning of the drug-induced pecking to the environment in which it first takes effect. In a first experiment, we attempted to suppress this conditioning by extensively pre-exposing the birds to the test environment and saline injection...

  18. Forming Competing Fear Learning and Extinction Memories in Adolescence Makes Fear Difficult to Inhibit

    Science.gov (United States)

    Baker, Kathryn D.; Richardson, Rick

    2015-01-01

    Fear inhibition is markedly impaired in adolescent rodents and humans. The present experiments investigated whether this impairment is critically determined by the animal's age at the time of fear learning or their age at fear extinction. Male rats (n = 170) were tested for extinction retention after conditioning and extinction at different ages.…

  19. Commentary about fear of movement

    OpenAIRE

    K. Meyer

    2010-01-01

    Chronic pain influences many aspects of a patient’s life and often results in physical disability. There are many concepts to explain this condition of disability. For example, several psychological variables like coping with pain, depression, hypervigilance, catastrophizing and fear avoidance are considered in literature to play an important role. In Vlaeyen’s model of fear avoidance, he proposes that in a first step negative affectivity and threatening illness information could trigger the ...

  20. Non-classical conditional probability and the quantum no-cloning theorem

    Science.gov (United States)

    Niestegge, Gerd

    2015-09-01

    The quantum mechanical no-cloning theorem for pure states is generalized and transfered to the quantum logics with a conditional probability calculus in a rather abstract, though simple and basic fashion without relying on a tensor product construction or finite dimension as required in other generalizations.

  1. Fear of Fear and the Anxiety Disorders.

    Science.gov (United States)

    Chambless, Dianne L.

    The fear of fear present in agoraphobics can be broken down into a fear of the body sensations associated with the panic attacks that plague agoraphobics and maladaptive thoughts about the possible consequences of panic. In a retrospective examination of clinical files, 32 agoraphobic patients were compared to 36 patients with simple social…

  2. Information about the model's unconditioned stimulus and response in vicarious classical conditioning.

    Science.gov (United States)

    Hygge, S

    1976-06-01

    Four groups with 16 observers each participated in a differential, vicarious conditioning experiment with skin conductance responses as the dependent variable. The information available to the observer about the model's unconditioned stimulus and response was varied in a 2 X 2 factorial design. Results clearly showed that information about the model's unconditioned stimulus (a high or low dB level) was not necessary for vicarious instigation, but that information about the unconditioned response (a high or low emotional aversiveness) was necessary. Data for conditioning of responses showed almost identical patterns to those for vicarious instigation. To explain the results, a distinction between factors necessary for the development and elicitation of vicariously instigated responses was introduced, and the effectiveness of information about the model's response on the elicitation of vicariously instigated responses was considered in terms of an expansion of Bandura's social learning theory. PMID:1271236

  3. Classical conditioning in borderline personality disorder: an fMRI study.

    Science.gov (United States)

    Krause-Utz, Annegret; Keibel-Mauchnik, Jana; Ebner-Priemer, Ulrich; Bohus, Martin; Schmahl, Christian

    2016-06-01

    Previous research suggests disturbed emotional learning and memory in borderline personality disorder (BPD). Studies investigating the neural correlates of aversive differential delay conditioning in BPD are currently lacking. We aimed to investigate acquisition, within-session extinction, between-session extinction recall, and reacquisition. We expected increased activation in the insula, amygdala, and anterior cingulate, and decreased prefrontal activation in BPD patients. During functional magnetic resonance imaging, 27 medication-free female BPD patients and 26 female healthy controls (HC) performed a differential delay aversive conditioning paradigm. An electric shock served as unconditioned stimulus, two neutral pictures as conditioned stimuli (CS+/CS-). Dependent variables were blood-oxygen-level-dependent response, skin conductance response (SCR), and subjective ratings (valence, arousal). No significant between-group differences in brain activation were found [all p(FDR) > 0.05]. Within-group comparisons for CS+unpaired > CS- revealed increased insula activity in BPD patients but not in HC during early acquisition; during late acquisition, both groups recruited fronto-parietal areas [p(FDR)  CS during extinction. During extinction recall, there was a trend for stronger SCR to CS+ > CS in BPD patients. Amygdala habituation to CS+paired (CS+ in temporal contingency with the aversive event) during acquisition was found in HC but not in patients. Our findings suggest altered temporal response patterns in terms of increased vigilance already during early acquisition and delayed extinction processes in individuals with BPD. PMID:25814470

  4. Molecular Specificity of Multiple Hippocampal Processes Governing Fear Extinction

    OpenAIRE

    Radulovic, Jelena; Tronson, Natalie C

    2010-01-01

    Over many years, fear extinction has been conceptualized as one dominant process, new inhibitory learning, which serves to dampen previously acquired fear. Here we present an alternative view, that brain region-specific processing of representations, expectations and emotional attributes of the fear-provoking event, recruits unique mechanisms that interdependently contribute to the conditioning and extinction of fear. The co-occurrence of these mechanisms within the fear circuit can thus be t...

  5. Omission of expected reward sensitizes the brain dopaminergic system of classically conditioned Atlantic salmon

    DEFF Research Database (Denmark)

    Vindas, M.A.; Höglund, Erik; Folkedal, O.;

    across treatments and generations is one particularly attractive feature of fish model systems. Both animal welfare considerations and fundamental scientific questions regarding the evolution of learning and memory have directed particular attention towards possible cognitive and emotional processes in....... There was also a general downregulation of dopamine receptor D1 gene expression in the telencephalon of OER groups, which suggests a coping mechanism in response to unbalanced DA metabolism. These results indicate that animals subjected to unpredictable reward conditions develop a senzitation of the DA...

  6. Synaptic Plasticity and NO-cGMP-PKG Signaling Coordinately Regulate ERK-Driven Gene Expression in the Lateral Amygdala and in the Auditory Thalamus Following Pavlovian Fear Conditioning

    Science.gov (United States)

    Ota, Kristie T.; Monsey, Melissa S.; Wu, Melissa S.; Young, Grace J.; Schafe, Glenn E.

    2010-01-01

    We have recently hypothesized that NO-cGMP-PKG signaling in the lateral nucleus of the amygdala (LA) during auditory fear conditioning coordinately regulates ERK-driven transcriptional changes in both auditory thalamic (MGm/PIN) and LA neurons that serve to promote pre- and postsynaptic alterations at thalamo-LA synapses, respectively. In the…

  7. Classicality condition on a system observable in a quantum measurement and a relative-entropy conservation law

    Science.gov (United States)

    Kuramochi, Yui; Ueda, Masahito

    2015-03-01

    We consider the information flow on a system observable X corresponding to a positive-operator-valued measure under a quantum measurement process Y described by a completely positive instrument from the viewpoint of the relative entropy. We establish a sufficient condition for the relative-entropy conservation law which states that the average decrease in the relative entropy of the system observable X equals the relative entropy of the measurement outcome of Y , i.e., the information gain due to measurement. This sufficient condition is interpreted as an assumption of classicality in the sense that there exists a sufficient statistic in a joint successive measurement of Y followed by X such that the probability distribution of the statistic coincides with that of a single measurement of X for the premeasurement state. We show that in the case when X is a discrete projection-valued measure and Y is discrete, the classicality condition is equivalent to the relative-entropy conservation for arbitrary states. The general theory on the relative-entropy conservation is applied to typical quantum measurement models, namely, quantum nondemolition measurement, destructive sharp measurements on two-level systems, a photon counting, a quantum counting, homodyne and heterodyne measurements. These examples except for the nondemolition and photon-counting measurements do not satisfy the known Shannon-entropy conservation law proposed by Ban [M. Ban, J. Phys. A: Math. Gen. 32, 1643 (1999), 10.1088/0305-4470/32/9/012], implying that our approach based on the relative entropy is applicable to a wider class of quantum measurements.

  8. Surface expression of hippocampal NMDA GluN2B receptors regulated by fear conditioning determines its contribution to memory consolidation in adult rats.

    Science.gov (United States)

    Sun, Yan-Yan; Cai, Wei; Yu, Jie; Liu, Shu-Su; Zhuo, Min; Li, Bao-Ming; Zhang, Xue-Han

    2016-01-01

    The number and subtype composition of N-methyl-d-aspartate receptor (NMDAR) at synapses determines their functional properties and role in learning and memory. Genetically increased or decreased amount of GluN2B affects hippocampus-dependent memory in the adult brain. But in some experimental conditions (e.g., memory elicited by a single conditioning trial (1 CS-US)), GluN2B is not a necessary factor, which indicates that the precise role of GluN2B in memory formation requires further exploration. Here, we examined the role of GluN2B in the consolidation of fear memory using two training paradigms. We found that GluN2B was only required for the consolidation of memory elicited by five conditioning trials (5 CS-US), not by 1 CS-US. Strikingly, the expression of membrane GluN2B in CA1was training-strength-dependently increased after conditioning, and that the amount of membrane GluN2B determined its involvement in memory consolidation. Additionally, we demonstrated the increases in the activities of cAMP, ERK, and CREB in the CA1 after conditioning, as well as the enhanced intrinsic excitability and synaptic efficacy in CA1 neurons. Up-regulation of membrane GluN2B contributed to these enhancements. These studies uncover a novel mechanism for the involvement of GluN2B in memory consolidation by its accumulation at the cell surface in response to behavioral training. PMID:27487820

  9. Surface expression of hippocampal NMDA GluN2B receptors regulated by fear conditioning determines its contribution to memory consolidation in adult rats

    Science.gov (United States)

    Sun, Yan-Yan; Cai, Wei; Yu, Jie; Liu, Shu-Su; Zhuo, Min; Li, Bao-Ming; Zhang, Xue-Han

    2016-01-01

    The number and subtype composition of N-methyl-d-aspartate receptor (NMDAR) at synapses determines their functional properties and role in learning and memory. Genetically increased or decreased amount of GluN2B affects hippocampus-dependent memory in the adult brain. But in some experimental conditions (e.g., memory elicited by a single conditioning trial (1 CS-US)), GluN2B is not a necessary factor, which indicates that the precise role of GluN2B in memory formation requires further exploration. Here, we examined the role of GluN2B in the consolidation of fear memory using two training paradigms. We found that GluN2B was only required for the consolidation of memory elicited by five conditioning trials (5 CS-US), not by 1 CS-US. Strikingly, the expression of membrane GluN2B in CA1was training-strength-dependently increased after conditioning, and that the amount of membrane GluN2B determined its involvement in memory consolidation. Additionally, we demonstrated the increases in the activities of cAMP, ERK, and CREB in the CA1 after conditioning, as well as the enhanced intrinsic excitability and synaptic efficacy in CA1 neurons. Up-regulation of membrane GluN2B contributed to these enhancements. These studies uncover a novel mechanism for the involvement of GluN2B in memory consolidation by its accumulation at the cell surface in response to behavioral training. PMID:27487820

  10. Classical entanglement

    OpenAIRE

    Danforth, Douglas G.

    2001-01-01

    Classical systems can be entangled. Entanglement is defined by coincidence correlations. Quantum entanglement experiments can be mimicked by a mechanical system with a single conserved variable and 77.8% conditional efficiency. Experiments are replicated for four particle entanglement swapping and GHZ entanglement.

  11. Fear Inhibition in High Trait Anxiety

    OpenAIRE

    Merel Kindt; Marieke Soeter

    2014-01-01

    Trait anxiety is recognized as an individual risk factor for the development of anxiety disorders but the neurobiological mechanisms remain unknown. Here we test whether trait anxiety is associated with impaired fear inhibition utilizing the AX+/BX- conditional discrimination procedure that allows for the independent evaluation of startle fear potentiation and inhibition of fear [1]. Sixty undergraduate students participated in the study - High Trait Anxious: n = 28 and Low Trait Anxious: n =...

  12. Understanding the breakdown of classic two-phase theory and spray atomization at engine-relevant conditions

    Science.gov (United States)

    Dahms, Rainer N.

    2016-04-01

    A generalized framework for multi-component liquid injections is presented to understand and predict the breakdown of classic two-phase theory and spray atomization at engine-relevant conditions. The analysis focuses on the thermodynamic structure and the immiscibility state of representative gas-liquid interfaces. The most modern form of Helmholtz energy mixture state equation is utilized which exhibits a unique and physically consistent behavior over the entire two-phase regime of fluid densities. It is combined with generalized models for non-linear gradient theory and for liquid injections to quantify multi-component two-phase interface structures in global thermal equilibrium. Then, the Helmholtz free energy is minimized which determines the interfacial species distribution as a consequence. This minimal free energy state is demonstrated to validate the underlying assumptions of classic two-phase theory and spray atomization. However, under certain engine-relevant conditions for which corroborating experimental data are presented, this requirement for interfacial thermal equilibrium becomes unsustainable. A rigorously derived probability density function quantifies the ability of the interface to develop internal spatial temperature gradients in the presence of significant temperature differences between injected liquid and ambient gas. Then, the interface can no longer be viewed as an isolated system at minimal free energy. Instead, the interfacial dynamics become intimately connected to those of the separated homogeneous phases. Hence, the interface transitions toward a state in local equilibrium whereupon it becomes a dense-fluid mixing layer. A new conceptual view of a transitional liquid injection process emerges from a transition time scale analysis. Close to the nozzle exit, the two-phase interface still remains largely intact and more classic two-phase processes prevail as a consequence. Further downstream, however, the transition to dense-fluid mixing

  13. The prelimbic cortex uses higher-order cues to modulate both the acquisition and expression of conditioned fear.

    Directory of Open Access Journals (Sweden)

    Melissa Judith Sharpe

    2015-01-01

    Full Text Available The prelimbic (PL cortex allows rodents to adapt their responding under changing experimental circumstances. In line with this, the PL cortex has been implicated in strategy set shifting, attentional set shifting, the resolution of response conflict, and the modulation of attention towards predictive stimuli. One interpretation of this research is that the PL cortex is involved in using information garnered from higher-order cues in the environment to modulate how an animal responds to environmental stimuli. However, data supporting this view of PL function in the aversive domain are lacking. In the following experiments, we attempted to answer two questions. Firstly, we wanted to investigate whether the role of the PL cortex in using higher-order cues to influence responding generalizes across appetitive and aversive domains. Secondly, as much of the research has focused on a role for the PL cortex in performance, we wanted to assess whether this region is also involved in the acquisition of hierarchal associations which facilitate an ability to use higher-order cues to modulate responding. In order to answer these questions, we assessed the impact of PL inactivation during both the acquisition and expression of a contextual bi-conditional discrimination. A contextual bi-conditional discrimination involves presenting two stimuli. In one context, one stimulus is paired with shock while the other is presented without shock. In another context, these contingencies are reversed. Thus, animals have to use the present contextual cues to disambiguate the significance of the stimulus and respond appropriately. We found that PL inactivation disrupted both the encoding and expression of these context-dependent associations. This supports a role for the PL cortex in allowing higher-order cues to modulate both learning about, and responding towards, different cues. We discuss these findings in the broader context of functioning in the medial prefrontal

  14. Immediate extinction promotes the return of fear.

    Science.gov (United States)

    Merz, Christian J; Hamacher-Dang, Tanja C; Wolf, Oliver T

    2016-05-01

    Accumulating evidence indicates that immediate extinction is less effective than delayed extinction in attenuating the return of fear. This line of fear conditioning research impacts the proposed onset of psychological interventions after threatening situations. In the present study, forty healthy men were investigated in a differential fear conditioning paradigm with fear acquisition in context A, extinction in context B, followed by retrieval testing in both contexts 24h later to test fear renewal. Differently coloured lights served as conditioned stimuli (CS): two CS (CS+) were paired with an electrical stimulation that served as unconditioned stimulus, the third CS was never paired (CS-). Extinction took place immediately after fear acquisition or 24h later. One CS+ was extinguished whereas the second CS+ remained unextinguished to control for different time intervals between fear acquisition and retrieval testing. Immediate extinction led to larger skin conductance responses during fear retrieval to both the extinguished and unextinguished CS relative to the CS-, indicating a stronger return of fear compared to delayed extinction. Taken together, immediate extinction is less potent than delayed extinction and is associated with a stronger renewal effect. Thus, the time-point of psychological interventions relative to the offset of threatening situations needs to be carefully considered to prevent relapses. PMID:26995309

  15. Memory suppression trades prolonged fear and sleep-dependent fear plasticity for the avoidance of current fear

    Science.gov (United States)

    Kuriyama, Kenichi; Honma, Motoyasu; Yoshiike, Takuya; Kim, Yoshiharu

    2013-07-01

    Sleep deprivation immediately following an aversive event reduces fear by preventing memory consolidation during homeostatic sleep. This suggests that acute insomnia might act prophylactically against the development of posttraumatic stress disorder (PTSD) even though it is also a possible risk factor for PTSD. We examined total sleep deprivation and memory suppression to evaluate the effects of these interventions on subsequent aversive memory formation and fear conditioning. Active suppression of aversive memory impaired retention of event memory. However, although the remembered fear was more reduced in sleep-deprived than sleep-control subjects, suppressed fear increased, and seemed to abandon the sleep-dependent plasticity of fear. Active memory suppression, which provides a psychological model for Freud's ego defense mechanism, enhances fear and casts doubt on the potential of acute insomnia as a prophylactic measure against PTSD. Our findings bring into question the role of sleep in aversive-memory consolidation in clinical PTSD pathophysiology.

  16. 消退训练对大鼠条件性恐惧行为及海马CA1区突触超微结构的影响%Effects of extinction training on conditioned fear behaviour and synaptic structure in hippocampal CA1 area in fear conditioned rats

    Institute of Scientific and Technical Information of China (English)

    张丽丽; 李培培; 李敏; 韦美; 彭李

    2012-01-01

    Objective To determine the effect of fear extinction training on the behaviours and the ultrastructure of hippocampal CA1 area in fear conditioned rats. Methods Forty male adult SD rats were randomly divided into native group (re =8), extinction control group (re = 16) and extinction group (re = 16). In 24 h after fear condition was established by reference instruction in the later 2 groups, extinction training was carried out in the extinction group and extinction retention test was performed in 7 and 21 d after fear extinction. The test was performed in 8 and 22 d in extinction control group. The changes of synaptic structure in CA1 of hippocampus were observed at 7 and 21 d after fear extinction. Results Compared with the extinction control group, the scores of extinction retention was significantly increased (P<0.01) at 7 and 21 d after extinction in the extinction group. There was no significant difference between extinction group and native group at 7 and 21 d. At 7 d after extinction training, the synaptic density was significantly higher in extinction group than that in the extinction control group (P <0.05 ) , and there was no difference among groups at 21 d. Compared with native group, the width of synaptic gap was significantly lower at 7 and 21 d after extinction training in extinction group ( P <0.01, 0. 05 ). At 21 d, the width of synaptic gap was significantly lower in the extinction group than that in the control group (P <0. 05). But there was no significant difference between the extinction control group and native group at 7 and 21 d after extinction. Compared with native group, at 7 and 21 d after extinction training, postsynaptic density (PSD) was significantly thicker in extinction group (P<0.01). And at 21 d, the density was significantly thicker in extinction group than that in the extinction control group (P < 0.05 ). There was no significant difference among the groups in active zone length. Conclusion Fear extinction training changes

  17. Neuroleptic drugs revert the contextual fear conditioning deficit presented by spontaneously hypertensive rats: a potential animal model of emotional context processing in schizophrenia?

    Science.gov (United States)

    Calzavara, Mariana Bendlin; Medrano, Wladimir Agostini; Levin, Raquel; Kameda, Sonia Regina; Andersen, Monica Levy; Tufik, Sergio; Silva, Regina Helena; Frussa-Filho, Roberto; Abílio, Vanessa Costhek

    2009-07-01

    Schizophrenia, bipolar disorder, and attention deficit/hyperactivity disorder (ADHD) present abnormalities in emotion processing. A previous study showed that the spontaneously hypertensive rats (SHR), a putative animal model of ADHD, present reduced contextual fear conditioning (CFC). The aim of the present study was to characterize the deficit in CFC presented by SHR. Adult male normotensive Wistar rats and SHR were submitted to the CFC task. Sensitivity of the animals to the shock and the CFC performance after repeated exposure to the task were investigated. Pharmacological characterization consisted in the evaluation of the effects of the following drugs administered previously to the acquisition of the CFC: pentylenetetrazole (anxiogenic) and chlordiazepoxide (anxiolytic); methylphenidate and amphetamine (used for ADHD); lamotrigine, carbamazepine, and valproic acid (mood stabilizers); haloperidol, ziprasidone, risperidone, amisulpride, and clozapine (neuroleptic drugs); metoclopramide and SCH 23390 (dopamine antagonists without antipsychotic properties); and ketamine (a psychotomimmetic). The effects of paradoxical sleep deprivation (that worsens psychotic symptoms) and the performance in a latent inhibition protocol (an animal model of schizophrenia) were also verified. No differences in the sensitivity to the shock were observed. The repeated exposure to the CFC task did not modify the deficit in CFC presented by SHR. Considering pharmacological treatments, only the neuroleptic drugs reversed this deficit. This deficit was potentiated by proschizophrenia manipulations. Finally, a deficit in latent inhibition was also presented by SHR. These findings suggest that the deficit in CFC presented by SHR could be a useful animal model to study abnormalities in emotional context processing related to schizophrenia. PMID:18281713

  18. Effects of chromium and chromium + vitamin C combination on metabolic, oxidative, and fear responses of broilers transported under summer conditions

    Science.gov (United States)

    Perai, A. H.; Kermanshahi, H.; Moghaddam, H. Nassiri; Zarban, A.

    2015-04-01

    A total of 240 female broilers (42 days old) were randomly assigned to four groups with six replicates and fed either a basal diet (two control groups) or a basal diet supplemented with either 1,200 μg Cr+3 from chromium (Cr) methionine/kg (Cr group) or 1,200 μg Cr+3 from Cr methionine plus 800 mg vitamin C (Vit C)/kg of diet (Cr + Vit C group). After 7 days on the dietary treatment, all groups except one of the controls were transported for 3 h under the summer conditions. Performance parameters were not influenced by dietary treatments. The plasma concentrations of insulin, triiodothyronine, triglyceride, and the ratio of triiodothyronine/thyroxin were decreased and the ratio of glucose/insulin was increased due to transport process. Road transportation also increased the plasma concentrations of protein, cholesterol, aspartate aminotransferase, and creatine kinase and decreased the concentration of low-density lipoprotein cholesterol in the Cr + Vit C group. The pretransport concentrations of insulin and triiodothyronine were highest in the Cr + Vit C group. The concentration of phosphorous was lower in the Cr group than that in the other groups after transport. No significant effects of dietary treatments were observed on the other biochemical parameters. Transport increased malondialdehyde concentration in the control group and did not change plasma total antioxidant capacity and erythrocyte glutathione peroxidase activity. Either in combination or alone, Cr increased plasma total antioxidant capacity (before transport P ≤ 0.05, after transport P = 0.07) but did not affect the concentration of malondialdehyde and activity of glutathione peroxidase. The duration of tonic immobility (TI) was similar between nontransported control chicks and transported chicks without any supplements. Pretreatment with Cr + Vit C significantly reduced the duration of TI.

  19. Classical Diophantine equations

    CERN Document Server

    1993-01-01

    The author had initiated a revision and translation of "Classical Diophantine Equations" prior to his death. Given the rapid advances in transcendence theory and diophantine approximation over recent years, one might fear that the present work, originally published in Russian in 1982, is mostly superseded. That is not so. A certain amount of updating had been prepared by the author himself before his untimely death. Some further revision was prepared by close colleagues. The first seven chapters provide a detailed, virtually exhaustive, discussion of the theory of lower bounds for linear forms in the logarithms of algebraic numbers and its applications to obtaining upper bounds for solutions to the eponymous classical diophantine equations. The detail may seem stark--- the author fears that the reader may react much as does the tourist on first seeing the centre Pompidou; notwithstanding that, Sprind zuk maintainsa pleasant and chatty approach, full of wise and interesting remarks. His emphases well warrant, ...

  20. NMDA receptors and fear extinction: implications for cognitive behavioral therapy

    OpenAIRE

    Davis, Michael

    2011-01-01

    Based primarily on studies that employ Pavlovian fear conditioning, extinction of conditioned fear has been found to be mediated by N-methyl-D-aspartate (NMDA) receptors in the amygdala and medial prefrontal cortex. This led to the discovery that an NMDA partial agonist, D-cycloserine, could facilitate fear extinction when given systemically or locally into the amygdala. Because many forms of cognitive behavioral therapy depend on fear extinction, this led to the successful use of D-cycloseri...

  1. Prefrontal NMDA receptors expressed in excitatory neurons control fear discrimination and fear extinction.

    Science.gov (United States)

    Vieira, Philip A; Corches, Alex; Lovelace, Jonathan W; Westbrook, Kevin B; Mendoza, Michael; Korzus, Edward

    2015-03-01

    N-methyl-D-aspartate receptors (NMDARs) are critically involved in various learning mechanisms including modulation of fear memory, brain development and brain disorders. While NMDARs mediate opposite effects on medial prefrontal cortex (mPFC) interneurons and excitatory neurons, NMDAR antagonists trigger profound cortical activation. The objectives of the present study were to determine the involvement of NMDARs expressed specifically in excitatory neurons in mPFC-dependent adaptive behaviors, specifically fear discrimination and fear extinction. To achieve this, we tested mice with locally deleted Grin1 gene encoding the obligatory NR1 subunit of the NMDAR from prefrontal CamKIIα positive neurons for their ability to distinguish frequency modulated (FM) tones in fear discrimination test. We demonstrated that NMDAR-dependent signaling in the mPFC is critical for effective fear discrimination following initial generalization of conditioned fear. While mice with deficient NMDARs in prefrontal excitatory neurons maintain normal responses to a dangerous fear-conditioned stimulus, they exhibit abnormal generalization decrement. These studies provide evidence that NMDAR-dependent neural signaling in the mPFC is a component of a neural mechanism for disambiguating the meaning of fear signals and supports discriminative fear learning by retaining proper gating information, viz. both dangerous and harmless cues. We also found that selective deletion of NMDARs from excitatory neurons in the mPFC leads to a deficit in fear extinction of auditory conditioned stimuli. These studies suggest that prefrontal NMDARs expressed in excitatory neurons are involved in adaptive behavior. PMID:25615540

  2. Involvement of the ipsilateral and contralateral cerebellum in the acquisition of unilateral classical eyeblink conditioning in guinea pigs

    Institute of Scientific and Technical Information of China (English)

    Bo HU; Xi LIN; Lushuai HUANG; Li YANG; Hua FENG; Jianfeng SUI

    2009-01-01

    Aim:The aim of this study was to evaluate the relative contributions of the ipsilateral and contralateral cerebellum to the acquisition of unilateral classical eyeblink conditioning (EBCC).Methods: The unilateral EBCC was achieved using a binaural tone conditioned stimulus (CS) paired with a left airpuff unconditioned stimulus (US).A high-resolution potentiometer was used to monitor eyeblink responses.Guinea pigs received one CS-US session followed by three CS-US sessions (sessions 2 to 4),during which microinjections of muscimol,a GABAA receptor agonist,were performed to reversibly inactivate the cerebellum unilaterally prior to training.To test whether any learning had occurred during these inactivation sessions,training was continued for six more CS-US sessions (sessions 5 to 10) without any inactivation.Results: Animals with inactivation of the left cerebellum had no signs of left conditioned response (CR) during sessions 2 to 4,and their CR acquisition during sessions 5 to 10 was not distinguishable from that of control animals during sessions 2 to 7.In contrast,animals with inactivation of the right cerebellum acquired left CRs during sessions 2 to 4,although their CR acquisition was significantly retarded during session 2.In addition,microinjections of muscimol into the right cerebellum did not affect left neuro-behavioral activity.Finally,microinjections of muscimol into either the left or the right cerebellum did not affect the performance of tone-airpuff evoked unconditioned response (UR).Conclusion: In contrast to the essential role of the ipsilateral cerebellum,the contralateral cerebellum is potentially involved in the acquisition of unilateral EBCC during the early stage of training.

  3. Fears and Phobias

    Science.gov (United States)

    ... the situation calls for. Many people have a fear of public speaking . Whether it's giving a report in class, speaking ... cloudy. A guy with social phobia experiences intense fear of public speaking or interacting, and may be afraid to answer ...

  4. A neurocomputational model of classical conditioning phenomena: a putative role for the hippocampal region in associative learning.

    Science.gov (United States)

    Moustafa, Ahmed A; Myers, Catherine E; Gluck, Mark A

    2009-06-18

    Some existing models of hippocampal function simulate performance in classical conditioning tasks using the error backpropagation algorithm to guide learning (Gluck, M.A., and Myers, C.E., (1993). Hippocampal mediation of stimulus representation: a computational theory. Hippocampus, 3(4), 491-516.). This algorithm is not biologically plausible because it requires information to be passed backward through layers of nodes and assumes that the environment provides information to the brain about what correct outputs should be. Here, we show that the same information-processing function proposed for the hippocampal region in the Gluck and Myers (1993) model can also be implemented in a network without using the backpropagation algorithm. Instead, our newer instantiation of the theory uses only (a) Hebbian learning methods which match more closely with synaptic and associative learning mechanisms ascribed to the hippocampal region and (b) a more plausible representation of input stimuli. We demonstrate here that this new more biologically plausible model is able to simulate various behavioral effects, including latent inhibition, acquired equivalence, sensory preconditioning, negative patterning, and context shift effects. In addition, the newer model is able to address some new phenomena including the effect of the number of training trials on blocking and overshadowing. PMID:19379717

  5. Trib3 is developmentally and nutritionally regulated in the brain but is dispensable for spatial memory, fear conditioning and sensing of amino acid-imbalanced diet.

    Directory of Open Access Journals (Sweden)

    Tiit Örd

    Full Text Available Tribbles homolog 3 (TRIB3 is a mammalian pseudokinase that is induced in neuronal cell cultures in response to cell death-inducing stresses, including neurotrophic factor deprivation. TRIB3 is an inhibitor of activating transcription factor 4 (ATF4, the central transcriptional regulator in the eukaryotic translation initiation factor 2α (eIF2α phosphorylation pathway that is involved in the cellular stress response and behavioral processes. In this article, we study the expression of Trib3 in the mouse brain, characterize the brain morphology of mice with a genetic ablation of Trib3 and investigate whether Trib3 deficiency alters eIF2α-dependent cognitive abilities. Our data show that the consumption of a leucine-deficient diet induces Trib3 expression in the anterior piriform cortex, the brain region responsible for detecting essential amino acid intake imbalance. However, the aversive response to leucine-devoid diet does not differ in Trib3 knockout and wild type mice. Trib3 deletion also does not affect long-term spatial memory and reversal learning in the Morris water maze and auditory or contextual fear conditioning. During embryonic development, Trib3 expression increases in the brain and persists in the early postnatal stadium. Neuroanatomical characterization of mice lacking Trib3 revealed enlarged lateral ventricles. Thus, although the absence of Trib3 does not alter the eIF2α pathway-dependent cognitive functions of several areas of the brain, including the hippocampus, amygdala and anterior piriform cortex, Trib3 may serve a role in other central nervous system processes and molecular pathways.

  6. The advances of fear

    International Nuclear Information System (INIS)

    This book treats of four sensible topics of the last decade - the nuclear industry, the cloning, Internet and the greenhouse effect - in order to analyze the irrational or organized fears among the public: what do we fear and why? How this fear is shown? Which questions need to be answered and how? (J.S.)

  7. A climate of fear

    DEFF Research Database (Denmark)

    Garner, Tom Alexander; Grimshaw, Mark Nicholas

    2011-01-01

    This paper proposes a framework that incorporates fear, acoustics, thought processing and digital game sound theory; with the potential to not only improve understanding of our relationship with fear, but also generate a foundation for reliable and significant manipulation of the fear experience....

  8. Phobias and preparedness: the selective, automatic, and encapsulated nature of fear.

    Science.gov (United States)

    Mineka, Susan; Ohman, Arne

    2002-11-15

    We describe evidence for an evolved module for fear elicitation and fear learning with four primary characteristics. First, it is preferentially activated by stimuli related to survival threats in evolutionary history. Thus, fear-relevant stimuli lead to superior conditioning of aversive associations compared with fear-irrelevant stimuli. Second, the module is automatically activated by fear-relevant stimuli, meaning that fear activation occurs before conscious cognitive analysis of the stimulus can occur. Third, the fear module is relatively impenetrable to conscious cognitive control, and fear conditioning with fear-relevant stimuli can occur even with subliminal conditioned stimuli. Fourth, the amygdala seems to be the central brain area dedicated to the fear module. Finally, we propose that there are two levels of fear conditioning, with an emotional level that is relatively independent of the cognitive contingency level, each mediated by different brain areas. PMID:12437934

  9. Ion association in concentrated NaCl brines from ambient to supercritical conditions: results from classical molecular dynamics simulations

    Directory of Open Access Journals (Sweden)

    Collings Matthew D

    2002-11-01

    Full Text Available Highly concentrated NaCl brines are important geothermal fluids; chloride complexation of metals in such brines increases the solubility of minerals and plays a fundamental role in the genesis of hydrothermal ore deposits. There is experimental evidence that the molecular nature of the NaCl–water system changes over the pressure–temperature range of the Earth's crust. A transition of concentrated NaCl–H2O brines to a "hydrous molten salt" at high P and T has been argued to stabilize an aqueous fluid phase in the deep crust. In this work, we have done molecular dynamic simulations using classical potentials to determine the nature of concentrated (0.5–16 m NaCl–water mixtures under ambient (25°C, 1 bar, hydrothermal (325°C, 1 kbar and deep crustal (625°C, 15 kbar conditions. We used the well-established SPCE model for water together with the Smith and Dang Lennard-Jones potentials for the ions (J. Chem. Phys., 1994, 100, 3757. With increasing temperature at 1 kbar, the dielectric constant of water decreases to give extensive ion-association and the formation of polyatomic (NanClmn-m clusters in addition to simple NaCl ion pairs. Large polyatomic (NanClmn-m clusters resemble what would be expected in a hydrous NaCl melt in which water and NaCl were completely miscible. Although ion association decreases with pressure, temperatures of 625°C are not enough to overcome pressures of 15 kbar; consequently, there is still enhanced Na–Cl association in brines under deep crustal conditions.

  10. Combined Neuropeptide S and D-Cycloserine Augmentation Prevents the Return of Fear in Extinction-Impaired Rodents: Advantage of Dual versus Single Drug Approaches

    Science.gov (United States)

    Maurer, Verena; Murphy, Conor; Schmuckermair, Claudia; Muigg, Patrick; Neumann, Inga D.; Whittle, Nigel

    2016-01-01

    Background: Despite its success in treating specific anxiety disorders, the effect of exposure therapy is limited by problems with tolerability, treatment resistance, and fear relapse after initial response. The identification of novel drug targets facilitating fear extinction in clinically relevant animal models may guide improved treatment strategies for these disorders in terms of efficacy, acceleration of fear extinction, and return of fear. Methods: The extinction-facilitating potential of neuropeptide S, D-cycloserine, and a benzodiazepine was investigated in extinction-impaired high anxiety HAB rats and 129S1/SvImJ mice using a classical cued fear conditioning paradigm followed by extinction training and several extinction test sessions to study fear relapse. Results: Administration of D-cycloserine improved fear extinction in extinction-limited, but not in extinction-deficient, rodents compared with controls. Preextinction neuropeptide S caused attenuated fear responses in extinction-deficient 129S1/SvImJ mice at extinction training onset and further reduced freezing during this session. While the positive effects of either D-cycloserine or neuropeptide S were not persistent in 129S1/SvImJ mice after 10 days, the combination of preextinction neuropeptide S with postextinction D-cycloserine rendered the extinction memory persistent and context independent up to 5 weeks after extinction training. This dual pharmacological adjunct to extinction learning also protected against fear reinstatement in 129S1/SvImJ mice. Conclusions: By using the potentially nonsedative anxiolytic neuropeptide S and the cognitive enhancer D-cycloserine to facilitate deficient fear extinction, we provide here the first evidence of a purported efficacy of a dual over a single drug approach. This approach may render exposure sessions less aversive and more efficacious for patients, leading to enhanced protection from fear relapse in the long term. PMID:26625894

  11. NR2A- and NR2B-Containing NMDA Receptors in the Prelimbic Medial Prefrontal Cortex Differentially Mediate Trace, Delay, and Contextual Fear Conditioning

    Science.gov (United States)

    Gilmartin, Marieke R.; Kwapis, Janine L.; Helmstetter, Fred J.

    2013-01-01

    Activation of "N"-methyl-D-aspartate receptors (NMDAR) in the prelimbic medial prefrontal cortex (PL mPFC) is necessary for the acquisition of both trace and contextual fear memories, but it is not known how specific NR2 subunits support each association. The NR2B subunit confers unique properties to the NMDAR and may differentially…

  12. Neonatal lesions of orbital frontal areas 11/13 in monkeys alter goal-directed behavior but spare fear conditioning and safety signal learning.

    Directory of Open Access Journals (Sweden)

    Andy M Kazama

    2014-03-01

    Full Text Available Recent studies in monkeys have demonstrated that damage to the lateral subfields of orbital frontal cortex (OFC areas 11/13 yields profound changes in flexible modulation of goal-directed behaviors and a lack in fear regulation. Yet, little consideration has been placed on its role in emotional and social development throughout life. The current study investigated the effects of neonatal lesions of the OFC on the flexible modulation of goal-directed behaviors and fear responses in monkeys. Infant monkeys received neonatal lesions of OFC areas 11/13 or sham-lesions during the first post-natal week. Modulation of goal-directed behaviors was measured with a devaluation task at 3-4 years and 6-7 years. Modulation of fear reactivity by safety signals was assessed with the AX+/BX- potentiated-startle paradigm at 6-7 years. Similar to adult-onset OFC lesions, selective neonatal lesions of OFC areas 11/13 yielded a failure to modulate behavioral responses guided by changes in reward value, but spared the ability to modulate fear responses in the presence of safety signals. These results suggest that these areas play a critical role in the development of behavioral adaptation during goal-directed behaviors, but not, or less so, in the development of the ability to process emotionally salient stimuli and to modulate emotional reactivity using environmental contexts, which could be supported by other OFC subfields, such as the most ventromedial subfields (i.e. areas 14/25. Given similar impaired decision-making abilities and spared modulation of fear followed both neonatal lesions of either OFC areas 11 and 13 or amygdala (Kazama et al., 2012; Kazama & Bachevalier, 2013, the present results suggest that interactions between these two neural structures play a critical role in the development of behavioral adaptation; an ability essential for the self-regulation of emotion and behavior that assures the maintenance of successful social relationships.

  13. Fear expression and return of fear following threat instruction with or without direct contingency experience.

    Science.gov (United States)

    Mertens, Gaëtan; Kuhn, Manuel; Raes, An K; Kalisch, Raffael; De Houwer, Jan; Lonsdorf, Tina B

    2016-08-01

    Prior research showed that mere instructions about the contingency between a conditioned stimulus (CS) and an unconditioned stimulus (US) can generate fear reactions to the CS. Little is known, however, about the extent to which actual CS-US contingency experience adds anything beyond the effect of contingency instructions. Our results extend previous studies on this topic in that it included fear potentiated startle as an additional dependent variable and examined return of fear (ROF) following reinstatement. We observed that CS-US pairings can enhance fear reactions beyond the effect of contingency instructions. Moreover, for all measures of fear, instructions elicited immediate fear reactions that could not be completely overridden by subsequent situational safety information. Finally, ROF following reinstatement for instructed CS+s was unaffected by actual experience. In summary, our results demonstrate the power of contingency instructions and reveal the additional impact of actual experience of CS-US pairings. PMID:25966279

  14. Blinded by fear? Prior exposure to fearful faces enhances attentional processing of task-irrelevant stimuli.

    Science.gov (United States)

    Berggren, Nick; Derakshan, Nazanin

    2013-01-01

    Threatening information has been shown to both capture attention and enhance sensory processing. Recent evidence has also suggested that exposure to fearful stimuli may enhance perceptual processing of subsequently presented information, as well as increase attentional capacity. However, these results are inconsistent with other findings that fearful stimuli reduce task-irrelevant distraction and improve selective attention. Here, we investigated the effect of prior exposure to fearful faces on performance in the Eriksen flanker task. Across experiments, fearful cues led to increased task-irrelevant distraction for items positioned across visual space, in contrast to other emotional expressions and inverted face items, and under conditions of attentional load. Findings support the view that fearful images enhance attentional capacity, allowing one to attend to as much visual information as possible when danger is implied. Conflicting findings on the effect of fear and selective attention are discussed. PMID:23510073

  15. Adolescent social defeat alters N-methyl-d-aspartic acid receptor expression and impairs fear learning in adulthood.

    Science.gov (United States)

    Novick, Andrew M; Mears, Mackenzie; Forster, Gina L; Lei, Yanlin; Tejani-Butt, Shanaz M; Watt, Michael J

    2016-05-01

    Repeated social defeat of adolescent male rats results in adult mesocortical dopamine hypofunction, impaired working memory, and increased contextual anxiety-like behavior. Given the role of glutamate in dopamine regulation, cognition, and fear and anxiety, we investigated potential changes to N-methyl-d-aspartic acid (NMDA) receptors following adolescent social defeat. As both NMDA receptors and mesocortical dopamine are implicated in the expression and extinction of conditioned fear, a separate cohort of rats was challenged with a classical fear conditioning paradigm to investigate whether fear learning is altered by adolescent defeat. Quantitative autoradiography was used to measure 3H-MK-801 binding to NMDA receptors in regions of the medial prefrontal cortex, caudate putamen, nucleus accumbens, amygdala and hippocampus. Assessment of fear learning was achieved using an auditory fear conditioning paradigm, with freezing toward the auditory tone used as a measure of conditioned fear. Compared to controls, adolescent social defeat decreased adult NMDA receptor expression in the infralimbic region of the prefrontal cortex and central amygdala, while increasing expression in the CA3 region of the hippocampus. Previously defeated rats also displayed decreased conditioned freezing during the recall and first extinction periods, which may be related to the observed decreases and increases in NMDA receptors within the central amygdala and CA3, respectively. The alteration in NMDA receptors seen following adolescent social defeat suggests that dysfunction of glutamatergic systems, combined with mesocortical dopamine deficits, likely plays a role in the some of the long-term behavioral consequences of social stressors in adolescence seen in both preclinical and clinical studies. PMID:26876136

  16. Role of the hippocampus in contextual modulation of fear extinction

    Institute of Scientific and Technical Information of China (English)

    Lingzhi Kong; Xihong Wu; Liang Li

    2008-01-01

    Fear extinction is an important form of emotional learning, and affects neural plasticity. Cue fear extinction is a classical form of inhibitory learning that can be used as an exposure-based treatment for phobia, because the long-term extinction memory produced during cue fear extinction can limit the over-expression of fear. The expression of this inhibitory memory partly depends on the context in which the extinction learning occurs. Studies such as transient inhibition, electrophysiology and brain imaging have proved that the hippocampus - an important structure in the limbic system - facilitates memory retrieval by contextual cues.Mediation of the hippocampus-medial prefrontal lobe circuit may be the neurobiological basis of this process.This article has reviewed the role of the hippocampus in the learning and retrieval of fear extinction.Contextual modulation of fear extinction may rely on a neural network consisting of the hippocampus, the medial prefrontal cortex and the amygdala.

  17. Scattering of H(D) from LiF(1 0 0) under fast grazing incidence conditions: To what extent is classical dynamics a useful tool?

    Energy Technology Data Exchange (ETDEWEB)

    Muzas, A.S. [Departamento de Química Módulo 13, Universidad Autónoma de Madrid, 28049 Madrid (Spain); Martín, F. [Departamento de Química Módulo 13, Universidad Autónoma de Madrid, 28049 Madrid (Spain); Instituto Madrileño de Estudios Avanzados en Nanociencia (IMDEA-nanociencia), Cantoblanco, 28049 Madrid (Spain); Díaz, C., E-mail: cristina.diaz@uam.es [Departamento de Química Módulo 13, Universidad Autónoma de Madrid, 28049 Madrid (Spain)

    2015-07-01

    Diffraction experiments of atoms and molecules under fast grazing incidence conditions have opened a new field in surface science. This experimental effort calls for complementary theoretical studies, which would allow a detailed analysis of experimental data. Here, we have analyzed the ability of classical dynamics simulations to reproduce experimental results. To perform this study, a DFT (density functional theory) based potential energy surface, describing the interaction between a H atom and a LiF(1 0 0) surface, has been computed. Diffraction probabilities have been simulated by means of a classical binning method. Our results have been found to be in qualitative good agreement with recent experimental measurements.

  18. Zinc Transporter 3 Is Involved in Learned Fear and Extinction, but Not in Innate Fear

    Science.gov (United States)

    Martel, Guillaume; Hevi, Charles; Friebely, Olivia; Baybutt, Trevor; Shumyatsky, Gleb P.

    2010-01-01

    Synaptically released Zn[superscript 2+] is a potential modulator of neurotransmission and synaptic plasticity in fear-conditioning pathways. Zinc transporter 3 (ZnT3) knock-out (KO) mice are well suited to test the role of zinc in learned fear, because ZnT3 is colocalized with synaptic zinc, responsible for its transport to synaptic vesicles,…

  19. Effects of rapid eye movement sleep deprivation on fear extinction recall and prediction error signaling.

    Science.gov (United States)

    Spoormaker, Victor I; Schröter, Manuel S; Andrade, Kátia C; Dresler, Martin; Kiem, Sara A; Goya-Maldonado, Roberto; Wetter, Thomas C; Holsboer, Florian; Sämann, Philipp G; Czisch, Michael

    2012-10-01

    In a temporal difference learning approach of classical conditioning, a theoretical error signal shifts from outcome deliverance to the onset of the conditioned stimulus. Omission of an expected outcome results in a negative prediction error signal, which is the initial step towards successful extinction and may therefore be relevant for fear extinction recall. As studies in rodents have observed a bidirectional relationship between fear extinction and rapid eye movement (REM) sleep, we aimed to test the hypothesis that REM sleep deprivation impairs recall of fear extinction through prediction error signaling in humans. In a three-day design with polysomnographically controlled REM sleep deprivation, 18 young, healthy subjects performed a fear conditioning, extinction and recall of extinction task with visual stimuli, and mild electrical shocks during combined functional magnetic resonance imaging (fMRI) and skin conductance response (SCR) measurements. Compared to the control group, the REM sleep deprivation group had increased SCR scores to a previously extinguished stimulus at early recall of extinction trials, which was associated with an altered fMRI time-course in the left middle temporal gyrus. Post-hoc contrasts corrected for measures of NREM sleep variability also revealed between-group differences primarily in the temporal lobe. Our results demonstrate altered prediction error signaling during recall of fear extinction after REM sleep deprivation, which may further our understanding of anxiety disorders in which disturbed sleep and impaired fear extinction learning coincide. Moreover, our findings are indicative of REM sleep related plasticity in regions that also show an increase in activity during REM sleep. PMID:21826762

  20. Effect of prolonged traumatic context exposure on conditioned fear response%延长创伤环境暴露时间对条件性恐惧表达的影响

    Institute of Scientific and Technical Information of China (English)

    安献丽; 梁璟; 郑伦; 李幼虹; 王文忠; 郑希耕

    2009-01-01

    Objective To understand the effect of immediately prolonged context exposure on cued conditioning.Methods Prolonged or not prolonged traumatic context exposure(rats stayed 90 minutes or 2 minutes in train context after the last light-shock trial,that was 90 min group or 2 min group respectively)immediately after visual Pavlov fear conditioning train to extinct the fear response to traumatic context.Results Results showed that contextual fear memory was an important factor modulating cued conditioned fear response of rats.In traumatic context,the fear response to conditioned light of 90 min group was marginally significant low compared with 2 min group[freezing levels were(19.531±6.073)%,(46.094±10.427)%respectively,P=0.085],and the decrease of fear expression of 90 min group could last at least 35 days[freezing levels were(21.094±4.897)%,(74.219±9.481)%respectively for groups,P<0.01].Conclusion Immediately prolonged context exposure transfer the traumatic context as a"safe occasion setter",then decreased the fear response to discrete conditioned cues.This suggests that immediately prolong the traumatic environment exposure time might be a favorable way to prevent posttraumatic stress disorder.%目的 明确延长创伤后创伤环境的暴露时间对单一线索条件性恐惧表达的影响.方法 灯光线索条件性恐惧训练后延长动物在训练环境中的停留时间.结果 创伤后延长环境暴露时间能够消除动物对环境的恐惧,使之不能自发恢复.并因此抑制了对单一线索的条件性恐惧反应,主要表现为在创伤环境中,延长暴露组动物对灯光线索的条件性恐惧反应低于非延长暴露组[恐惧水平分别为(19.531±6.073)%,(46.094±10.427)%],达到边缘显著水平(P=0.085),且这种恐惧下调可以持续至少35d[延长暴露组与非延长暴露组的恐惧水平分别为(21.094±4.897)%,(74.219±9.481)%,P<0.01].结论 延长创伤环境暴露时间改变了对创伤环境的"恐惧"

  1. Fear in horses

    OpenAIRE

    Christensen, Janne Winther

    2006-01-01

    Fear is generally considered to be an undesirable emotional state that may reduce welfare, growth and reproductive performance in animals. Fear in horses is additionally problematic, because fear reactions can cause serious injury to both horse and human. Horses are primarily used for sports and leisure for a large number of children and young women. Unfortunately, horse riding ranks as one of the most dangerous sports in terms of the number and seriousness of accidents, and the ability of a ...

  2. Attachment Without Fear

    OpenAIRE

    Bell, David C.

    2009-01-01

    John Bowlby hypothesized an attachment system that interacts with caregiving, exploration, and fear systems in the brain, with a particular emphasis on fear. Neurobiological research confirms many of his hypotheses and also raises some new questions. A psychological model based on this neurobiological research is presented here. The model extends conventional attachment theory by describing additional attachment processes independent of fear. In this model, the attachment elements of trust, o...

  3. Inhibition of cognitive reappraisal on the negative valence facilitates extinction in conditioned fear%认知重评对负性效价的抑制促进条件性恐惧消退

    Institute of Scientific and Technical Information of China (English)

    廖素群; 郑希付

    2016-01-01

    认知重评能有效降低个体对情感刺激的负性情绪体验,但指导性认知重评在恐惧记忆治疗中效果存在争议。本文将认知重评范式与辨别式条件恐惧反应范式结合,以效价和US预期值为指标,探讨指导性认知重评训练对恐惧情绪习得和消退的影响效果。以低认知重评能力个体为被试,在实验前24 h进行指导性认知重评训练。条件性恐惧任务为期2天,第一天完成条件性恐惧的习得和消退任务,第二天完成条件性恐惧的再消退任务。结果显示,经过重评训练后个体在条件性恐惧任务中的恐惧情绪效价显著较低,说明认知重评有效降低低认知重评能力个体在急性应激状态下的负性情绪体验。所有被试均成功完成辨别式条件性恐惧的习得和消退任务,因此重评训练并不削弱个体对危险或者安全信息的辨别能力。但在条件性恐惧的消退过程中,认知重评指导训练加快了恐惧消退,且24 h后测得的条件性恐惧程度显著较低,说明指导性重评提高了条件性恐惧记忆的消退效率,并减弱了条件性恐惧的消退返回。%The negative cognitive bias is common in affective disorder patients, which is resistance to treatment and recovery. Cognitive reappraisal is an emotion regulation strategy that involves the process of changing the emotion response by reinterpreting the meaning of the emotional stimulus. It has been shown that cognitive reappraisal decreases negative cognitive and emotion valance effectively. Conditioned fear is an important model of affective disorder. However, whether reappraisal changes the negative cognitive and emotion in the conditioned fear is controversial. Here, we investigate whether the short-term cognitive reappraisal training could change the process of conditioned fear for individuals with low reappraisal ability and further reveal the influence of cognitive reappraisal on the

  4. Acquisition of blood, injury, and needle fears and phobias.

    Science.gov (United States)

    Kleinknecht, R A

    1994-11-01

    The origins of fear and phobia of blood, injury, and injections were investigated in a sample of 128 fearful university students. Based on Mutilation Questionnaire scores, subjects were designated as common fear, high fear, or phobic. Ss reports of their onset experiences obtained from structured interviews were categorized into one or more acquisition pathways of conditioning, vicarious observation, and information. Of the 73% of Ss who recalled one or more onset experiences, 76% reported conditioning-like events as the primary pathway with the majority reporting fear-related UCSs. Vicarious experiences were reported as primary by 20% and 3% reported information as being primary in their fear onset. Severity of fear was unrelated to the pathway by which it was acquired, to whether the onset was recalled, and if recalled, whether it was due to a single or to multiple traumatic events. Results are discussed in terms of methodological problems of memory issues and means by which data are collected. PMID:7993325

  5. Timing of extinction relative to acquisition: A parametric analysis of fear extinction in humans

    NARCIS (Netherlands)

    S.D. Norrholm; B. Vervliet; T. Jovanovic; W. Boshoven; K.M. Myers; M. Davis; B.O. Rothbaum; E.J. Duncan

    2008-01-01

    Fear extinction is a reduction in conditioned fear following repeated exposure to the feared cue in the absence of any aversive event. Extinguished fear often reappears after extinction through spontaneous recovery. Animal studies suggest that spontaneous recovery can be abolished if extinction occu

  6. Memory suppression trades prolonged fear and sleep-dependent fear plasticity for the avoidance of current fear

    OpenAIRE

    Kenichi Kuriyama; Motoyasu Honma; Takuya Yoshiike; Yoshiharu Kim

    2013-01-01

    Sleep deprivation immediately following an aversive event reduces fear by preventing memory consolidation during homeostatic sleep. This suggests that acute insomnia might act prophylactically against the development of posttraumatic stress disorder (PTSD) even though it is also a possible risk factor for PTSD. We examined total sleep deprivation and memory suppression to evaluate the effects of these interventions on subsequent aversive memory formation and fear conditioning. Active suppress...

  7. Failure of classical traffic and transportation theory: The maximization of the network throughput maintaining free flow conditions in network

    CERN Document Server

    Kerner, Boris S

    2016-01-01

    We show that the minimization of travel times in a network as generally accepted in classical traffic and transportation theories deteriorates the traffic system through a considerable increase in the probability of traffic breakdown in the network. We introduce a network characteristic {\\it minimum network capacity} that shows that rather than the minimization of travel times in the network, the minimization of the probability of traffic breakdown in the network maximizes the network throughput at which free flow persists in the whole network.

  8. Olfactory instruction for fear: neural system analysis.

    Directory of Open Access Journals (Sweden)

    Newton Sabino Canteras

    2015-08-01

    Full Text Available Studies using cat odor have led to detailed mapping of neural sites engaged in innate and contextual fear responses. Here, we reviewed three lines of work examining the dynamics of the neural systems that organize innate and learned fear responses to cat odor. In the first, we explored the neural systems involved in innate fear responses and in the different stages of fear conditioning to cat odor (i.e., acquisition and expression, with a particular emphasis on the role of the dorsal premammillary nucleus (PMd and the dorsolateral periaqueductal gray (PAGdl as key sites that influence innate and contextual conditioning. In the second line of studies, we reviewed how chemical stimulation of these sites (i.e., the PMd and PAGdl may serve as a useful unconditioned stimulus in an olfactory fear conditioning paradigm; these experiments provide an interesting perspective for the understanding of learned fear to predator odor. Finally, in the third line of studies, we explored the fact that neutral odors that acquire an aversive valence in a shock-paired conditioning paradigm may mimic predator odor and mobilize elements of the hypothalamic predator-responsive circuit.

  9. Fifty million Frenchmen have few nuclear fears

    Energy Technology Data Exchange (ETDEWEB)

    DuPont, R.L.

    A psychiatrist examines why France chose the nuclear power option in 1974 and expects for it to generate 75% of its power by 1990 in contrast to the US rejection and fear of nuclear power. The fear dominating US media coverage since 1968 is classic phobic thinking. A comparison of US and French attitudes reveals that French nuclear plants are tourist attractions, accepted by residents as both safe and of economic benefit. Accidents are examined realistically in France without the what if drama given to US incidents. Some political problems have developed and recent anti-nuclear activities are taken seriously, but the opposition was not based on fear. Public acceptance in France is partly due to a lack of energy alternatives and a pragmatism that works against phobias. (DCK)

  10. Fifty million Frenchmen have few nuclear fears

    International Nuclear Information System (INIS)

    A psychiatrist examines why France chose the nuclear power option in 1974 and expects for it to generate 75% of its power by 1990 in contrast to the US rejection and fear of nuclear power. The fear dominating US media coverage since 1968 is classic phobic thinking. A comparison of US and French attitudes reveals that French nuclear plants are tourist attractions, accepted by residents as both safe and of economic benefit. Accidents are examined realistically in France without the what if drama given to US incidents. Some political problems have developed and recent anti-nuclear activities are taken seriously, but the opposition was not based on fear. Public acceptance in France is partly due to a lack of energy alternatives and a pragmatism that works against phobias

  11. Stressor controllability modulates fear extinction in humans

    OpenAIRE

    Hartley, Catherine A.; Gorun, Alyson; Reddan, Marianne C.; Ramirez, Franchesca; Phelps, Elizabeth A.

    2013-01-01

    Traumatic events are proposed to play a role in the development of anxiety disorders, however not all individuals exposed to extreme stress experience a pathological increase in fear. Recent studies in animal models suggest that the degree to which one is able to control an aversive experience is a critical factor determining its behavioral consequences. In this study, we examined whether stressor controllability modulates subsequent conditioned fear expression in humans. Participants were ra...

  12. Individual differences in recovery from traumatic fear

    OpenAIRE

    Holmes, Andrew; Singewald, Nicolas

    2012-01-01

    Although exposure to major psychological trauma is unfortunately common, risk for related neuropsychiatric conditions, such as post-traumatic stress disorder (PTSD), varies greatly among individuals. Fear extinction offers a tractable and translatable behavioral readout of individual differences in learned recovery from trauma. Studies in rodent substrains and subpopulations are providing new insights into neural system dysfunctions associated with impaired fear extinction. Rapid progress is ...

  13. Existence and uniqueness for one-phase Stefan problems of non-classical heat equations with temperature boundary condition at a fixed face

    Directory of Open Access Journals (Sweden)

    Adriana C. Briozzo

    2006-02-01

    Full Text Available We prove the existence and uniqueness, local in time, of a solution for a one-phase Stefan problem of a non-classical heat equation for a semi-infinite material with temperature boundary condition at the fixed face. We use the Friedman-Rubinstein integral representation method and the Banach contraction theorem in order to solve an equivalent system of two Volterra integral equations.

  14. Non-Markov scattering and condition of applicability of quasi-classical description of collisions in plasma

    International Nuclear Information System (INIS)

    It is shown that scattering of a probe particle in plasma is not always described by diffusion process due to non-Markov nature of pulse transmission. Three are three various states in particle braking by plasma: stages specific for short and long time intervals when scattering is of non-diffusion nature, and the stage of intermediate time intervals when scattering may be described by diffusion process. Mechanism responsible for non-diffusion nature of scattering during long time intervals results in a new term of application of the classical mechanics to describe collisions in plasma

  15. Classical antiparticles

    Energy Technology Data Exchange (ETDEWEB)

    Costella, J.P.; McKellar, B.H.J.; Rawlinson, A.A.

    1997-03-01

    We review how antiparticles may be introduced in classical relativistic mechanics, and emphasize that many of their paradoxical properties can be more transparently understood in the classical than in the quantum domain. (authors). 13 refs., 1 tab.

  16. An experimental demonstration that fear, but not disgust, is associated with return of fear in phobias.

    Science.gov (United States)

    Edwards, Sarah; Salkovskis, Paul M

    2006-01-01

    It has been suggested that disgust, rather than anxiety, may be important in some phobias. Correlational studies have been ambiguous, indicating either that disgust increases phobic anxiety or that phobic anxiety potentiates disgust. In the experimental study reported here, disgust and phobic anxiety were manipulated in the context of habituation to phobic stimuli. Spider fearful participants were randomly allocated to conditions in which neutral, disgusting, and phobic anxiety provoking stimuli were introduced into a video-based spider phobic habituation sequence. Exposure to the phobic stimulus resulted in a return of self-reported fear and disgust levels. However, exposure to disgusting stimulus increased disgust levels, but not anxiety levels. Results are most consistent with the hypothesis that fear enhances the disgust response in phobias, but that disgust alone does not enhance the fear response. Previously observed links between disgust and spider phobia may be a consequence of fear enhancing disgust. PMID:16325114

  17. Timing of Extinction Relative to Acquisition: A Parametric Analysis of Fear Extinction in Humans

    OpenAIRE

    Norrholm, Seth D.; Vervliet, Bram; Jovanovic, Tanja; Boshoven, William; Myers, Karyn M.; Davis, Michael; Rothbaum, Barbara; Duncan, Erica J.

    2008-01-01

    Fear extinction is a reduction in conditioned fear following repeated exposure to the feared cue in the absence of any aversive event. Extinguished fear often reappears after extinction through spontaneous recovery. Animal studies suggest that spontaneous recovery can be abolished if extinction occurs within minutes of acquisition. However, a limited number of human extinction studies have shown that short interval extinction does not prevent the return of fear. For this reason, we performed ...

  18. Fear Extinction Memory Consolidation Requires Potentiation of Pontine-Wave Activity during REM Sleep

    OpenAIRE

    Datta, Subimal; O'Malley, Matthew W .

    2013-01-01

    Sleep plays an important role in memory consolidation within multiple memory systems including contextual fear extinction memory, but little is known about the mechanisms that underlie this process. Here, we show that fear extinction training in rats, which extinguished conditioned fear, increased both slow-wave sleep and rapid-eye movement (REM) sleep. Surprisingly, 24 h later, during memory testing, only 57% of the fear-extinguished animals retained fear extinction memory. We found that the...

  19. An exploratory research : Fear and the need of security interplay as a business mechanism

    OpenAIRE

    Beltrán Alanis, Martha Alicia; Cruz Sánchez, Javier Arnulfo

    2011-01-01

    Background: Humanity builds and writes its history. Overtime the need of feeling secure has been present originated from an emotion, a condition and reaction: the fear of threats or danger. The impact of human fear over the humanity behaviour leads for searching ways of reducing such fear. Consequently, security companies have a potential opportunity for fulfilling this human need reducing the phenomenon of fear. Some organisations and companies discovered that human fear can be used as tool ...

  20. Intergenerational transmission of emotional trauma through amygdala-dependent mother-to-infant transfer of specific fear

    OpenAIRE

    Debiec, Jacek; Sullivan, Regina Marie

    2014-01-01

    Despite clinical evidence that specific fear is transmitted across generations, we have little understanding of mechanisms. Here, we model social transmission of mother-to-infant fear in rodents. We show that maternal fear responses to a conditioned fear odor are sufficient to induce robust fear learning throughout infancy, with robust retention. Assessment of mechanism showed that maternal fear expression increases pups’ stress hormone corticosterone and amygdala activation to induce this cu...

  1. THE FEAR OF FEAR CONCEPT - EVIDENCE IN FAVOR OF MULTIDIMENSIONALITY

    NARCIS (Netherlands)

    ARRINDELL, WA

    1993-01-01

    In recent years, questions have been raised regarding the dimensionality of existing measures of fear of fear. This is an important issue that needs to be addressed if the dimensions(s) of any scale purporting to assess fear of fear are to guide theory and research. One of the most widely used measu

  2. Fear load: The psychophysiological over-expression of fear as an intermediate phenotype associated with trauma reactions.

    Science.gov (United States)

    Norrholm, Seth Davin; Glover, Ebony M; Stevens, Jennifer S; Fani, Negar; Galatzer-Levy, Isaac R; Bradley, Bekh; Ressler, Kerry J; Jovanovic, Tanja

    2015-11-01

    Psychophysiological measures of fear expression provide observable intermediate phenotypes of fear-related symptoms. Research Domain Criteria (RDoC) advocate using neurobiological intermediate phenotypes that provide dimensional correlates of psychopathology. Negative Valence Systems in the RDoC matrix include the construct of acute threat, which can be measured on a physiological level using potentiation of the acoustic startle reflex assessed via electromyography recordings of the orbicularis oculi muscle. Impairments in extinction of fear-potentiated startle due to high levels of fear (termed fear load) during the early phases of extinction have been observed in posttraumatic stress disorder (PTSD). The goals of the current work were to examine dimensional associations between fear-related symptoms of PTSD and fear load variables to test their validity as an intermediate phenotype. We examined extinction of fear-potentiated startle in a cohort (n=269) of individuals with a broad range of civilian trauma exposure (range 0-13 traumatic events per person, mean=3.5). Based on previously reported findings, we hypothesized that fear load would be significantly associated with intrusion and fear memories of an index traumatic event. The results indicated that early extinction was correlated with intrusive thoughts (p=0.0007) and intense physiological reactions to trauma reminders (p=0.036). Degree of adult or childhood trauma exposure, and depression severity were not associated with fear load. After controlling for age, sex, race, income, level of prior trauma, and level of fear conditioning, fear load during extinction was still significantly predictive of intrusive thoughts (p=0.004). The significance of these findings is that they support dimensional associations with symptom severity rather than diagnostic category and, as such, fear load may emerge as a transdiagnostic intermediate phenotype expressed across fear-related disorders (e.g., specific phobia, social

  3. The Biology of Fear

    OpenAIRE

    Adolphs, Ralph

    2013-01-01

    Each of us has felt afraid, and we can all recognize fear in many animal species. Yet there is no consensus in the scientific study of fear. Some argue that “fear” is a psychological construct rather than discoverable through scientific investigation. Others argue that the term “fear” cannot properly be applied to animals because we cannot know whether they feel afraid. Studies in rodents show that there are highly specific brain circuits for fear, whereas findings from human neuroimaging see...

  4. In the vicious circle of fear

    International Nuclear Information System (INIS)

    Fear is the great driving force, the basic effect, without which there would be no adaption to new living conditions, and no provision for the future. But fear has a positive influence only as long as it does not gain the upper hand, for then it makes human beings blind and stifles activity. What is important, and will remain so, is the equilibrium between fear and courage, caution and the desire for action, optimism und pessimism. This equilibrium has now been disturbed in the western countries - and only here. Our present fears give rise to hardly any positive measures, but prevent provision for the future. We are threatened with failure due to the manipulated conversion of fear from the maintenance of life to an effect which destroys life. In this way we got into a vicious circle of fear: we must try to weaken the imagined dangers by emphasising the true conditions. The author discusses how the viscious circle can be broken. (orig.) 891 UA/orig. 892 MKO

  5. Oxytocin Facilitates Pavlovian Fear Learning in Males.

    Science.gov (United States)

    Eckstein, Monika; Scheele, Dirk; Patin, Alexandra; Preckel, Katrin; Becker, Benjamin; Walter, Annika; Domschke, Katharina; Grinevich, Valery; Maier, Wolfgang; Hurlemann, René

    2016-03-01

    In human evolution, social group living and Pavlovian fear conditioning have evolved as adaptive mechanisms promoting survival and reproductive success. The evolutionarily conserved hypothalamic peptide oxytocin is a key modulator of human sociality, but its effects on fear conditioning are still elusive. In the present randomized controlled study involving 97 healthy male subjects, we therefore employed functional magnetic resonance imaging and simultaneous skin conductance response (SCR) measures to characterize the modulatory influence of intranasal oxytocin (24 IU) on Pavlovian fear conditioning. We found that the peptide strengthened conditioning on both the behavioral and neural levels. Specifically, subjects exhibited faster task-related responses and enhanced SCRs to fear-associated stimuli in the late phase of conditioning, which was paralleled by heightened activity in cingulate cortex subregions in the absence of changes in amygdala function. This speaks against amygdalocentric views of oxytocin having pure anxiolytic-like effects. Instead, it suggests that the peptide enables extremely rapid and flexible adaptation to fear signals in social contexts, which may confer clear evolutionary advantages but could also elevate vulnerability for the pathological sequelae of interpersonal trauma. PMID:26272050

  6. Fear: The Teachers' Teacher.

    Science.gov (United States)

    Agne, Karen

    1996-01-01

    Looks at the effects of fear in the classroom and offers suggestions for teachers in dealing with the issue: self-acceptance, other-orientation, trust, patience, self-awareness, and journal writing. (JOW)

  7. The Fears of Adolescents

    Science.gov (United States)

    Bamber, James H.

    1974-01-01

    This study investigated the self-reported fears and some personality characteristics of a sample of 1112 adolescents ranging in age from 12 to 18 years (attending grammar and secondary schools in Northern Ireland). (CS)

  8. Effects of the swimming exercise on the consolidation and persistence of auditory and contextual fear memory.

    Science.gov (United States)

    Faria, Rodolfo Souza; Gutierres, Luís Felipe Soares; Sobrinho, Fernando César Faria; Miranda, Iris do Vale; Reis, Júlia Dos; Dias, Elayne Vieira; Sartori, Cesar Renato; Moreira, Dalmo Antonio Ribeiro

    2016-08-15

    Exposure to negative environmental events triggers defensive behavior and leads to the formation of aversive associative memory. Cellular and molecular changes in the central nervous system underlie this memory formation, as well as the associated behavioral changes. In general, memory process is established in distinct phases such as acquisition, consolidation, evocation, persistence, and extinction of the acquired information. After exposure to a particular event, early changes in involved neural circuits support the memory consolidation, which corresponds to the short-term memory. Re-exposure to previously memorized events evokes the original memory, a process that is considered essential for the reactivation and consequent persistence of memory, ensuring that long-term memory is established. Different environmental stimuli may modulate the memory formation process, as well as their distinct phases. Among the different environmental stimuli able of modulating memory formation is the physical exercise which is a potent modulator of neuronal activity. There are many studies showing that physical exercise modulates learning and memory processes, mainly in the consolidation phase of the explicit memory. However, there are few reports in the literature regarding the role of physical exercise in implicit aversive associative memory, especially at the persistence phase. Thus, the present study aimed to investigate the relationship between swimming exercise and the consolidation and persistence of contextual and auditory-cued fear memory. Male Wistar rats were submitted to sessions of swimming exercise five times a week, over six weeks. After that, the rats were submitted to classical aversive conditioning training by a pairing tone/foot shock paradigm. Finally, rats were evaluated for consolidation and persistence of fear memory to both auditory and contextual cues. Our results demonstrate that classical aversive conditioning with tone/foot shock pairing induced

  9. Dietary Cholesterol Concentration and Duration Degrade Long-Term Memory of Classical Conditioning of the Rabbit’s Nictitating Membrane Response

    Directory of Open Access Journals (Sweden)

    Bernard G. Schreurs

    2012-01-01

    Full Text Available A rabbit model of Alzheimer’s disease based on feeding a cholesterol diet for eight weeks shows sixteen hallmarks of the disease, including learning and memory changes. Although we have shown 2% cholesterol and copper in water can retard learning, other studies show feeding dietary cholesterol before learning can improve acquisition whereas feeding cholesterol after learning can degrade long-term memory. We explored this issue by manipulating cholesterol concentration and duration following classical trace conditioning of the rabbit’s nictitating membrane response and assessed conditioned responding after eight weeks on cholesterol. First, rabbits given trace classical conditioning followed by 0.5%, 1%, or 2% cholesterol for eight weeks showed body weight and serum cholesterol levels that were a function of dietary cholesterol. Although all concentrations of cholesterol showed some sign of retarding long-term memory, the level of memory retardation was correlated with serum cholesterol levels. Second, rabbits given trace conditioning followed by different durations of a 2% cholesterol diet combined with different durations of a 0% control diet for 8 weeks showed duration and timing of a 2% cholesterol diet were important in affecting recall. The data support the idea that dietary cholesterol may retard long-term memory.

  10. Classical eyeblink conditioning using electrical stimulation of caudal mPFC as conditioned stimulus is dependent on cerebellar interpositus nucleus in guinea pigs

    Institute of Scientific and Technical Information of China (English)

    Guang-yan WU; Juan YAO; Zheng-li FAN; Lang-qian ZHANG; Xuan LI; Chuang-dong ZHAO; Zhen-hua ZHOU; Jian-feng SUI

    2012-01-01

    Aim:To determine whether electrical stimulation of caudal medial prefrontal cortex (mPFC) as conditioned stimulus (CS) paired with airpuff unconditioned stimulus (US) was sufficient for establishing eyeblink conditioning in guinea pigs,and whether it was dependent on cerebellar interpositus nucleus.Methods:Thirty adult guinea pigs were divided into 3 conditioned groups,and trained on the delay eyeblink conditioning,short-trace eyeblink conditioning,and long-trace eyeblink conditioning paradigms,respectively,in which electrical stimulation of the right caudal mPFC was used as CS and paired with corneal airpuff US.A pseudo conditioned group of another 10 adult guinea pigs was given unpaired caudal mPFC electrical stimulation and the US.Muscimol (1 μg in 1 μL saline) and saline (1 μL) were infused into the cerebellar interpositus nucleus of the animals through the infusion cannula on d 11 and 12,respectively.Results:The 3 eyeblink conditioning paradigms have been successfully established in guinea pigs.The animals acquired the delay and short-trace conditioned responses more rapidly than long-trace conditioned responses.Muscimol infusion into the cerebellar interpositus nucleus markedly impaired the expression of the 3 eyeblink conditioned responses.Conclusion:Electrical stimulation of caudal mPFC is effective CS for establishing eyeblink conditioning in guinea pigs,and it is dependent on the cerebellar interpositus nucleus.

  11. Conceptual similarity promotes generalization of higher order fear learning

    OpenAIRE

    Dunsmoor, Joseph E.; White, Allison J.; LaBar, Kevin S.

    2011-01-01

    We tested the hypothesis that conceptual similarity promotes generalization of conditioned fear. Using a sensory preconditioning procedure, three groups of subjects learned an association between two cues that were conceptually similar, unrelated, or mismatched. Next, one of the cues was paired with a shock. The other cue was then reintroduced to test for fear generalization, as measured by the skin conductance response. Results showed enhanced fear generalization that correlated with trait a...

  12. Pathways of fear and anxiety in dentistry: A review

    OpenAIRE

    Carter, Ava Elizabeth; Carter, Geoff; Boschen, Mark; AlShwaimi, Emad; George, Roy

    2014-01-01

    The aim of this article was to analyze the theories underpinning dental fear, anxiety and phobias. To be included, articles must have been published between the years of 1949 and 2013 concerning fears and phobias within dentistry and/or psychiatry. Of 200 articles originally under review, 140 were included and reviewed by the authors.Five specific pathways relating to dental fear and anxiety were identified; Cognitive Conditioning, Informative, Visual Vicarious, Verbal Threat, and Parental. E...

  13. Fear of childbirth in pregnant women: External and internal factors.

    OpenAIRE

    Kashshapova, E. V.; Lopukhova, O. G.

    2015-01-01

    Fear of childbirth (FOC) is an important psychological problem that is studied worldwide because it affects the well-being of pregnant women. However, in Russia, this problem does not receive adequate attention among researchers. The purpose of the present study was to investigate the conditionality of fear of childbirth (FOC) in pregnant women by external and internal factors, which we assumed were the reasons for this fear. As external factors, we considered socio-demographic indicators (e....

  14. Fear of childbirth in pregnant women: external and internal factors

    OpenAIRE

    LOPUKHOVA OLGA G.; KASHSHAPOVA ELENA V.

    2015-01-01

    Fear of childbirth (FOC) is an important psychological problem that is studied worldwide because it affects the well-being of pregnant women. However, in Russia, this problem does not receive adequate attention among researchers. The purpose of the present study was to investigate the conditionality of fear of childbirth (FOC) in pregnant women by external and internal factors, which we assumed were the reasons for this fear. As external factors, we considered socio-demographic indicators (e....

  15. 女性生理周期对条件性恐惧习得和消退的影响%Influence of Female Menstrual Cycle on the Acquisition and Extinction of Conditioned Fear

    Institute of Scientific and Technical Information of China (English)

    金艳; 郑希付

    2015-01-01

    Animal studies have shown that estrogens exert important influence on the acquisition and extinction of conditioned fear, however, the gonadal hormone regulation of fear in human is not known. The purpose of the present study is to examine effects of female menstrual phases on the conditioned fear acquisition and extinction. Twenty female college students in luteal phase and 20 female college students in menses phase participated in the experiment. They were exposed to three conditions: 1) predictable aversive stimuli were signaled by a cue; 2) aversive stimuli were administered unpredictably; 3) no aversive stimuli were anticipated. Aversive unconditioned stimulus (US) expectancy was used to assess anxious responses to the threat cue and to contexts associated with each condition. The results showed that, at the acquisition stage, females in luteal phase (FL) showed higher US expectance for the conditioned context fear in N and P context than females in menses phase (FM); at the extinction stage, FL had a significantly higher US expectancy in N and P context compared to FM. In other words, the females of luteal phase acquired the conditioned context fear response more effectively and extinguished more slowly than females of menses phase. These data suggest that menstrual cycle can possibly influence the conditioned context fear responses in females. This phenomenon suggests that the gonadal hormone level of luteal phase may affect fear regulation.%动物研究显示, 雌激素调节条件性恐惧习得和消退, 但是, 人类的性激素对条件性恐惧习得和消退的影响还不太清楚.因此, 本研究以大学生为研究对象, 考察女性不同生理周期对条件性情境恐惧的习得和消退的影响.20名经前期和20名经期女被试暴露于3种情境下:无厌恶刺激情境(N)、可预测情境(P)和不可预测情境(U), 预测此 3 种情境下是否出现厌恶刺激.以在线索条件下和无线索条件下对厌恶刺激的主观

  16. Prefrontal neuronal assemblies temporally control fear behaviour.

    Science.gov (United States)

    Dejean, Cyril; Courtin, Julien; Karalis, Nikolaos; Chaudun, Fabrice; Wurtz, Hélène; Bienvenu, Thomas C M; Herry, Cyril

    2016-07-21

    Precise spike timing through the coordination and synchronization of neuronal assemblies is an efficient and flexible coding mechanism for sensory and cognitive processing. In cortical and subcortical areas, the formation of cell assemblies critically depends on neuronal oscillations, which can precisely control the timing of spiking activity. Whereas this form of coding has been described for sensory processing and spatial learning, its role in encoding emotional behaviour remains unknown. Fear behaviour relies on the activation of distributed structures, among which the dorsal medial prefrontal cortex (dmPFC) is known to be critical for fear memory expression. In the dmPFC, the phasic activation of neurons to threat-predicting cues, a spike-rate coding mechanism, correlates with conditioned fear responses and supports the discrimination between aversive and neutral stimuli. However, this mechanism does not account for freezing observed outside stimuli presentations, and the contribution of a general spike-time coding mechanism for freezing in the dmPFC remains to be established. Here we use a combination of single-unit and local field potential recordings along with optogenetic manipulations to show that, in the dmPFC, expression of conditioned fear is causally related to the organization of neurons into functional assemblies. During fear behaviour, the development of 4 Hz oscillations coincides with the activation of assemblies nested in the ascending phase of the oscillation. The selective optogenetic inhibition of dmPFC neurons during the ascending or descending phases of this oscillation blocks and promotes conditioned fear responses, respectively. These results identify a novel phase-specific coding mechanism, which dynamically regulates the development of dmPFC assemblies to control the precise timing of fear responses. PMID:27409809

  17. Generalisation of fear and avoidance along a semantic continuum.

    Science.gov (United States)

    Boyle, Sean; Roche, Bryan; Dymond, Simon; Hermans, Dirk

    2016-01-01

    Directly conditioned fear and avoidance readily generalises to dissimilar but conceptually related stimuli. Here, for the first time, we examined the conceptual/semantic generalisation of both fear and avoidance using real words (synonyms). Participants were first exposed to a differential fear conditioning procedure in which one word (e.g., "broth"; CS+) was followed with brief electric shock [unconditioned stimulus (US)] and another was not (e.g., "assist"; CS-). Next, an instrumental conditioning phase taught avoidance in the presence the CS+ but not the CS-. During generalisation testing, synonyms of the CS+ (e.g., "soup"; GCS+) and CS- (e.g., "help"; GCS-) were presented in the absence of shock. Conditioned fear and avoidance, measured via skin conductance responses, behavioural avoidance and US expectancy ratings, generalised to the semantically related, but not to the semantically unrelated, synonyms. Findings have implications for how natural language categories and concepts mediate the expansion of fear and avoidance repertoires in clinical contexts. PMID:25648156

  18. Young and Old Pavlovian Fear Memories Can Be Modified with Extinction Training during Reconsolidation in Humans

    Science.gov (United States)

    Steinfurth, Elisa C. K.; Kanen, Jonathan W.; Raio, Candace M.; Clem, Roger L.; Huganir, Richard L.; Phelps, Elizabeth A.

    2014-01-01

    Extinction training during reconsolidation has been shown to persistently diminish conditioned fear responses across species. We investigated in humans if older fear memories can benefit similarly. Using a Pavlovian fear conditioning paradigm we compared standard extinction and extinction after memory reactivation 1 d or 7 d following acquisition.…

  19. Visualization of Plasticity in Fear-Evoked Calcium Signals in Midbrain Dopamine Neurons

    Science.gov (United States)

    Gore, Bryan B.; Soden, Marta E.; Zweifel, Larry S.

    2014-01-01

    Dopamine is broadly implicated in fear-related processes, yet we know very little about signaling dynamics in these neurons during active fear conditioning. We describe the direct imaging of calcium signals of dopamine neurons during Pavlovian fear conditioning using fiber-optic confocal microscopy coupled with the genetically encoded calcium…

  20. The effect of positive mood induction on reducing reinstatement fear: Relevance for long term outcomes of exposure therapy

    OpenAIRE

    Zbozinek, Tomislav D.; Holmes, Emily A.; Craske, Michelle G.

    2015-01-01

    While exposure therapy is effective in treating anxiety, fear can return after exposure. Return of fear can be understood through mechanisms of extinction learning. One form of return of fear is reinstatement, or, the fear that results from an unsignaled unconditional stimulus (US) presentation after extinction. Though the conditional response (CR; e.g., fear) typically reduces during extinction, the excitatory conditional stimulus (CS+) valence remains negative. The more negative the CS+ val...

  1. Classical integrability

    Science.gov (United States)

    Torrielli, Alessandro

    2016-08-01

    We review some essential aspects of classically integrable systems. The detailed outline of the sections consists of: 1. Introduction and motivation, with historical remarks; 2. Liouville theorem and action-angle variables, with examples (harmonic oscillator, Kepler problem); 3. Algebraic tools: Lax pairs, monodromy and transfer matrices, classical r-matrices and exchange relations, non-ultralocal Poisson brackets, with examples (non-linear Schrödinger model, principal chiral field); 4. Features of classical r-matrices: Belavin–Drinfeld theorems, analyticity properties, and lift of the classical structures to quantum groups; 5. Classical inverse scattering method to solve integrable differential equations: soliton solutions, spectral properties and the Gel’fand–Levitan–Marchenko equation, with examples (KdV equation, Sine-Gordon model). Prepared for the Durham Young Researchers Integrability School, organised by the GATIS network. This is part of a collection of lecture notes.

  2. Daring to Fear: Optimizing the Encounter of Danger through Education

    Directory of Open Access Journals (Sweden)

    Alin Cristian

    2012-06-01

    Full Text Available Through its would-be extrication from education, fear just gets forced into a less detectable and hence more efficacious modus operandi characteristic of anxiety and deep boredom. Since proscribing fear protects students not against the danger it foreshadows but against acknowledging the existence thereof, a conditional acceptance of it might empower them to manage their lives superlatively. Being only bureaucratically objective when conveying threats to their future, as schools do, is a limitation imposed upon a more responsible, deeper-level intersubjective involvement to which fear holds the key. Schools are best placed for attempting to restore the public management of ‘individual’ fears.

  3. Emetophobia: A fear of vomiting.

    Science.gov (United States)

    Faye, Abhijeet D; Gawande, Sushil; Tadke, Rahul; Kirpekar, Vivek C; Bhave, Sudhir H

    2013-10-01

    Emetophobia is an intense, irrational fear of vomiting including fear of feeling nausea, seeing or hearing another person vomit, or seeing vomitus itself. It may occur at any age and we need to understand its symptomatology. We report a case of emetophobic child whose fear of vomiting started after an attack of acute appendicitis. In the initial stage, fear was limited to vomiting, later it became generalized to a fear of seeing the vomitus, worries that parents may suffer vomiting, fear of vomiting in public places followed by avoiding social activities. Patient improved on short course of anti-anxiety drugs and Graded Exposure Therapy. PMID:24459314

  4. Fear and Aggression in German Shepherd, Boxer and Rottweiler Dogs

    Directory of Open Access Journals (Sweden)

    Krassimira Uzunova

    2015-05-01

    Full Text Available As a result of long-term active fear, variable moods can occur – howling, whimpering, crying, tremor, tics, manias, depressions, etc. It is now acknowledged that fear and aggression are closely related. It is also known that the different dog breeds manifest a various extent of fear and aggression. The study aimed to provide answers to two questions - classification of factors invoking fear and aggression according to their significance and which of investigated dog breeds – German Shepherd, Rottweiler or Boxer is the most resistant to fear and aggression episodes? The exclusion of all factors on the cultivation of three breeds of dogs / they complied with the norms / found that the causes of fear aggressive conditions are listed as follows – first of fear and aggression depend on the temperament of the dog and on the second place of the breed origin, growing conditions and the associated level of primary and secondary socialization. Fear aggressive manifestations occur at least in dogs with sanguine and choleric temperament. Representatives of the breed "Boxer" and "German Shepherd" are at the same level on the manifestations of fear and aggression. Rottweiler breed is in third place in this direction.

  5. Comparison of inbred mouse substrains reveals segregation of maladaptive fear phenotypes

    Directory of Open Access Journals (Sweden)

    Stephanie J Temme

    2014-08-01

    Full Text Available Maladaptive fear, such as fear that is persistent or easily generalized to a nonthreatening stimuli, is associated with anxiety-related disorders in humans. In the laboratory, maladaptive fear can be modeled in rodents using Pavlovian fear conditioning. Recently, an inbred mouse strain known as 129S1/SvImJ, or 129S1 have been reported as exhibiting impairments in fear extinction and enhanced fear generalization. With a long-term goal of identifying segregating genetic markers of maladaptive fear, we used Pavlovian fear conditioning to characterize a closely related substrain designated as 129S6/SvEvTac, or 129S6. Here we report that, like 129S1 animals, 129S6 mice exhibit appropriate levels of fear upon conditioning, but are unable to extinguish fear memories once they are consolidated. Importantly, the maladaptive fear phenotype in this inbred stain can be segregated by sub-strain when probed using conditioning protocols designed to assess generalized fear. We find that unlike the 129S1 substrain, mice from the 129S6 sub-strain do not generalize conditioned fear to previously novel contexts and can learn to discriminate between two similar contexts when trained using a discrimination protocol. These results suggest that at least two forms of maladaptive fear (deficits in fear extinction and fear generalization can be can be functionally segregated, further suggesting that the underlying neurobiology is heritable. Given the observation that two closely related sub-strains can exhibit different constellations of maladaptive fear suggests that these findings could be exploited to facilitate the identification of candidate genes for anxiety-related disorders.

  6. Fearing religious satire

    DEFF Research Database (Denmark)

    Brink, Dennis Meyhoff

    The article examines the history of the fear of religious satire in modern Europe. The article argues that this fear primarily concerns the potential dissolution of 'the social bond of society' or 'the moral and social order'. From the 17th Century until today, censorship measures and blasphemy...... legislations are Thus primarily founded on arguments concerning moral, social or public order. The article furthermore argues that although anti-censorship satire gradually weakened the legitimacy of censorship, the notion of religion as 'the social bond of society' is still operative in contemporary blasphemy...

  7. Classical Tunneling

    CERN Document Server

    Cohn, A G; Rabinowitz, Mario

    2003-01-01

    A classical representation of an extended body over barriers of height greater than the energy of the incident body is shown to have many features in common with quantum tunneling as the center-of-mass literally goes through the barrier. It is even classically possible to penetrate any finite barrier with a body of arbitrarily low energy if the body is sufficiently long. A distribution of body lengths around the de Broglie wavelength leads to reasonable agreement with the quantum transmission coefficient.

  8. Classical Tunneling

    OpenAIRE

    Cohn, Arthur; Rabinowitz, Mario

    2003-01-01

    A classical representation of an extended body over barriers of height greater than the energy of the incident body is shown to have many features in common with quantum tunneling as the center-of-mass literally goes through the barrier. It is even classically possible to penetrate any finite barrier with a body of arbitrarily low energy if the body is sufficiently long. A distribution of body lengths around the de Broglie wavelength leads to reasonable agreement with the quantum transmission...

  9. Classical Motion

    OpenAIRE

    Mould, Richard A

    2003-01-01

    Preciously given rules allow conscious systems to be included in quantum mechanical systems. There rules are derived from the empirical experience of an observer who witnesses a quantum mechanical interaction leading to the capture of a single particle. In the present paper it is shown that purely classical changes experienced by an observer are consistent with these rules. Three different interactions are considered, two of which combine classical and quantum mechanical changes. The previous...

  10. Dorky Poll Scientific Fears

    CERN Multimedia

    2008-01-01

    The questions posed in yesterday's posts about hopes for 2008 were half of what we were asked by the Powers That Be. The other half: What scientific development do you fear you'll be blogging or reading about in 2008?

  11. Fear of the Formal

    DEFF Research Database (Denmark)

    du Gay, Paul; Lopdrup-Hjorth, Thomas

    2016-01-01

    term this ‘fear of the formal’, outlining key elements of its genealogy and exploring its contemporary manifestation in relation to recent and ongoing reforms of organisational life in a range of contexts. At the same time, we seek to indicate the continuing constitutive significance of formality...

  12. Animal Models of Fear Relapse

    OpenAIRE

    Goode, Travis D.; Maren, Stephen

    2014-01-01

    Whereas fear memories are rapidly acquired and enduring over time, extinction memories are slow to form and are susceptible to disruption. Consequently, behavioral therapies that involve extinction learning (e.g., exposure therapy) often produce only temporary suppression of fear and anxiety. This review focuses on the factors that are known to influence the relapse of extinguished fear. Several phenomena associated with the return of fear after extinction are discussed, including renewal, sp...

  13. Serotonin, Amygdala and Fear: Assembling the Puzzle

    Science.gov (United States)

    Bocchio, Marco; McHugh, Stephen B.; Bannerman, David M.; Sharp, Trevor; Capogna, Marco

    2016-01-01

    The fear circuitry orchestrates defense mechanisms in response to environmental threats. This circuitry is evolutionarily crucial for survival, but its dysregulation is thought to play a major role in the pathophysiology of psychiatric conditions in humans. The amygdala is a key player in the processing of fear. This brain area is prominently modulated by the neurotransmitter serotonin (5-hydroxytryptamine, 5-HT). The 5-HT input to the amygdala has drawn particular interest because genetic and pharmacological alterations of the 5-HT transporter (5-HTT) affect amygdala activation in response to emotional stimuli. Nonetheless, the impact of 5-HT on fear processing remains poorly understood.The aim of this review is to elucidate the physiological role of 5-HT in fear learning via its action on the neuronal circuits of the amygdala. Since 5-HT release increases in the basolateral amygdala (BLA) during both fear memory acquisition and expression, we examine whether and how 5-HT neurons encode aversive stimuli and aversive cues. Next, we describe pharmacological and genetic alterations of 5-HT neurotransmission that, in both rodents and humans, lead to altered fear learning. To explore the mechanisms through which 5-HT could modulate conditioned fear, we focus on the rodent BLA. We propose that a circuit-based approach taking into account the localization of specific 5-HT receptors on neurochemically-defined neurons in the BLA may be essential to decipher the role of 5-HT in emotional behavior. In keeping with a 5-HT control of fear learning, we review electrophysiological data suggesting that 5-HT regulates synaptic plasticity, spike synchrony and theta oscillations in the BLA via actions on different subcellular compartments of principal neurons and distinct GABAergic interneuron populations. Finally, we discuss how recently developed optogenetic tools combined with electrophysiological recordings and behavior could progress the knowledge of the mechanisms underlying 5

  14. Cortisol modifies extinction learning of recently acquired fear in men.

    Science.gov (United States)

    Merz, Christian Josef; Hermann, Andrea; Stark, Rudolf; Wolf, Oliver Tobias

    2014-09-01

    Exposure therapy builds on the mechanism of fear extinction leading to decreased fear responses. How the stress hormone cortisol affects brain regions involved in fear extinction in humans is unknown. For this reason, we tested 32 men randomly assigned to receive either 30 mg hydrocortisone or placebo 45 min before fear extinction. In fear acquisition, a picture of a geometrical figure was either partially paired (conditioned stimulus; CS+) or not paired (CS-) with an electrical stimulation (unconditioned stimulus; UCS). In fear extinction, each CS was presented again, but no UCS occurred. Cortisol increased conditioned skin conductance responses in early and late extinction. In early extinction, higher activation towards the CS- than to the CS+ was found in the amygdala, hippocampus and posterior parahippocampal gyrus. This pattern might be associated with the establishment of a new memory trace. In late extinction, the placebo compared with the cortisol group displayed enhanced CS+/CS- differentiation in the amygdala, medial frontal cortex and nucleus accumbens. A change from early deactivation to late activation of the extinction circuit as seen in the placebo group seems to be needed to enhance extinction and to reduce fear. Cortisol appears to interfere with this process thereby impairing extinction of recently acquired conditioned fear. PMID:23945999

  15. Does Religious Involvement Generate or Inhibit Fear of Crime?

    Directory of Open Access Journals (Sweden)

    Todd Matthews

    2011-09-01

    Full Text Available In victimology, fear of crime is understood as an emotional response to the perceived threat of crime. Fear of crime has been found to be affected by several variables besides local crime rates and personal experiences with victimization. This study examines the relationship between religion and fear of crime, an underexplored topic in the criminological literature. This gap is rather surprising given the central role religion has been found to play in shaping the attitudes and perceptions of congregants. In particular, religion has been found to foster generalized trust, which should engender lower levels of distrust or misanthropy, including that which is directed towards a general fear of crime. OLS regression was performed using data from the West Georgia Area Survey (n = 380. Controlling for demographic, community involvement, and political ideology variables, frequency of religious attendance was significantly and negatively associated with fear of property crime. This relationship remained even after a perceived neighborhood safety variable was introduced to the model. However, religious attendance was not significantly related to fear of violent crime, and religious orientation was unrelated to fear of property and violent crime. These results suggest that religious involvement conditionally reduces fear of crime, and the authors recommend that future research explore relationships between religion and fear of crime.

  16. Enhanced sensitization to animal, interpersonal, and intergroup fear-relevant stimuli (but no evidence for selective one-trial fear learning).

    Science.gov (United States)

    Lipp, Ottmar V; Cronin, Sophie L; Alhadad, Sakinah S J; Luck, Camilla C

    2015-11-01

    Selective sensitization has been proposed as an alternative explanation for enhanced responding to animal fear-relevant stimuli--snakes and spiders--during extinction of Pavlovian fear conditioning. The current study sought to replicate the phenomenon using a shock workup procedure as the sensitizing manipulation and to extend it to interpersonal and intergroup fear-relevant stimuli--angry faces and other-race faces. Assessment of selective sensitization was followed by a one-trial fear learning procedure. Selective sensitization, larger electrodermal responses to fear-relevant than to control stimuli after sensitization, or a larger increase in electrodermal responding to fear-relevant than to control stimuli after sensitization was observed across stimulus domains. However, the one-trial fear learning procedure failed to provide evidence for enhanced fear conditioning to fear-relevant stimuli. One-trial fear learning was either absent or present for fear-relevant and nonfear-relevant stimuli. The current study confirms that electrodermal responses to fear-relevant stimuli across stimulus domains are subject to selective sensitization. PMID:26283264

  17. Sex differences in fear extinction and involvements of extracellular signal-regulated kinase (ERK).

    Science.gov (United States)

    Matsuda, Shingo; Matsuzawa, Daisuke; Ishii, Daisuke; Tomizawa, Haruna; Sutoh, Chihiro; Shimizu, Eiji

    2015-09-01

    Stress-related disorders, such as post-traumatic stress disorder (PTSD) and panic disorders, are disproportionately prevalent in females. However, the biological mechanism underlying these sex differences in the prevalence rate remains unclear. In the present study, we examined sex differences in fear memory, fear extinction, and spontaneous recovery of fear. We investigated the presence of sex differences in recent and remote fear memory in mice using contextual fear conditioning, as well as sex differences in spontaneous recovery of fear memory using a consecutive fear extinction paradigm. We examined the number of fear extinction days required to prevent spontaneous recovery of fear in either sex. We investigated whether ovariectomy affected fear extinction and spontaneous recovery. We also measured the activation of extracellular signal-regulated kinase (ERK) 1 and 2 in the dorsal hippocampus and the medial prefrontal cortex following fear extinction sessions. In our results, we found no sex difference in recent or remote fear memory. However, females required more fear extinction sessions compared to males to prevent spontaneous recovery. Within-extinction freezing also differed between males and females. Moreover, females required more extinction sessions than males to increase ERK2 phosphorylation in the dorsal hippocampus. Our data suggest that contextual fear extinction was unstable in females compared to males and that such sex differences may be related to the ERK2 phosphorylation in the hippocampus. PMID:26079214

  18. An embodied biologically constrained model of foraging: from classical and operant conditioning to adaptive real-world behavior in DAC-X.

    Science.gov (United States)

    Maffei, Giovanni; Santos-Pata, Diogo; Marcos, Encarni; Sánchez-Fibla, Marti; Verschure, Paul F M J

    2015-12-01

    Animals successfully forage within new environments by learning, simulating and adapting to their surroundings. The functions behind such goal-oriented behavior can be decomposed into 5 top-level objectives: 'how', 'why', 'what', 'where', 'when' (H4W). The paradigms of classical and operant conditioning describe some of the behavioral aspects found in foraging. However, it remains unclear how the organization of their underlying neural principles account for these complex behaviors. We address this problem from the perspective of the Distributed Adaptive Control theory of mind and brain (DAC) that interprets these two paradigms as expressing properties of core functional subsystems of a layered architecture. In particular, we propose DAC-X, a novel cognitive architecture that unifies the theoretical principles of DAC with biologically constrained computational models of several areas of the mammalian brain. DAC-X supports complex foraging strategies through the progressive acquisition, retention and expression of task-dependent information and associated shaping of action, from exploration to goal-oriented deliberation. We benchmark DAC-X using a robot-based hoarding task including the main perceptual and cognitive aspects of animal foraging. We show that efficient goal-oriented behavior results from the interaction of parallel learning mechanisms accounting for motor adaptation, spatial encoding and decision-making. Together, our results suggest that the H4W problem can be solved by DAC-X building on the insights from the study of classical and operant conditioning. Finally, we discuss the advantages and limitations of the proposed biologically constrained and embodied approach towards the study of cognition and the relation of DAC-X to other cognitive architectures. PMID:26585942

  19. Fear of Negative Evaluation Moderates the Effect of Subliminal Fear Priming on Rejection of Unfair Offers in the Ultimatum Game.

    Science.gov (United States)

    Takagishi, Haruto; Fujii, Takayuki; Nishina, Kuniyuki; Okada, Hiroyuki

    2016-01-01

    The purpose of this study was to examine whether the tendency to fear negative evaluation moderates the effect of fear emotion on the rejection of unfair offers in the ultimatum game (UG). A photograph of a fearful face or landscape was displayed subliminally (i.e., for 10 ms) before the proposer's offer in the UG was presented to participants. We used the Fear of Negative Evaluation Scale (FNES) to measure participants' anxiety regarding negative evaluations from others. Results showed a significant interaction between FNES and condition (fearful face vs. landscape) in relation to the rejection of an unfair offer. Furthermore, the mean rejection rate of an unfair offer was significantly higher in the fearful face condition relative to that in the landscape condition among participants whose FNES scores were higher than the median; however, this difference was not observed in participants whose FNES scores were lower than the median. These results suggest that fear of negative evaluation moderates the effect of subliminal fear priming on the rejection of unfair offers in the UG, and that negative emotion induced by unconscious stimuli enhances rejection of these unfair offers. PMID:27549022

  20. Failure to overcome 'innate' fear: a developmental test of the non-associative model of fear acquisition.

    Science.gov (United States)

    Poulton, R; Waldie, K E; Menzies, R G; Craske, M G; Silva, P A

    2001-01-01

    The non-associative, Darwinian theory of fear acquisition proposes that some individuals fail to overcome biologically-relevant fears (e.g. height) because they (1) do not have sufficient safe exposure to the relevant stimuli early in life or (2) are poor habituators who have difficulty 'learning not to fear'. These two hypotheses were tested in a longitudinal birth cohort study. Study 1 found evidence for reduced exposure to height stimuli in childhood for individuals with a fear of heights compared to study members without fear. Study 2 found evidence for higher levels of stress reactivity (a proxy for habituation) in childhood and adolescence among 18-year-old height phobics compared to study members with dental phobia and those with no fear. The results were discussed in relation to recent findings suggesting that some evolutionary-relevant fears may appear in the absence of traumatic 'learning' experiences. The merits of adding a fourth, non-associative pathway to Rachman's [Rachman, S. (1977)]. The conditioning theory of fear acquisition: a critical examination. Behaviour Research and Therapy, 15, 375-387) three pathways model of fear acquisition were briefly considered. PMID:11125722

  1. Complementary Roles for Amygdala and Periaqueductal Gray in Temporal-Difference Fear Learning

    Science.gov (United States)

    Cole, Sindy; McNally, Gavan P.

    2009-01-01

    Pavlovian fear conditioning is not a unitary process. At the neurobiological level multiple brain regions and neurotransmitters contribute to fear learning. At the behavioral level many variables contribute to fear learning including the physical salience of the events being learned about, the direction and magnitude of predictive error, and the…

  2. Inactivation of the Infralimbic but Not the Prelimbic Cortex Impairs Consolidation and Retrieval of Fear Extinction

    Science.gov (United States)

    Laurent, Vincent; Westbrook, R. Frederick

    2009-01-01

    Rats were subjected to one or two cycles of context fear conditioning and extinction to study the roles of the prelimbic cortex (PL) and infralimbic cortex (IL) in learning and relearning to inhibit fear responses. Inactivation of the PL depressed fear responses across the first or second extinction but did not impair learning or relearning fear…

  3. Classical Motion

    CERN Document Server

    Mould, R A

    2003-01-01

    Preciously given rules allow conscious systems to be included in quantum mechanical systems. There rules are derived from the empirical experience of an observer who witnesses a quantum mechanical interaction leading to the capture of a single particle. In the present paper it is shown that purely classical changes experienced by an observer are consistent with these rules. Three different interactions are considered, two of which combine classical and quantum mechanical changes. The previously given rules support all of these cases. Key Words: brain states, conscious observer, detector, measurement, probability current, state reduction, von Neumann, wave collapse.

  4. Looking beyond Fear and Extinction Learning: Considering Novel Treatment Targets for Anxiety

    OpenAIRE

    Britton, Jennifer C.; Evans, Travis C.; Hernandez, Michael V.

    2014-01-01

    Fear conditioning studies provide valuable insight into how fears are learned and extinguished. Previous work focuses on fear and extinction learning to understand and treat anxiety disorders. However, a cascade of cognitive processes that extend beyond learning may also yield therapeutic targets for anxiety disorders. Throughout this review, we will discuss recent findings of fear generalization, memory consolidation, and reconsolidation. Factors related to effectiveness, efficiency and dura...

  5. Interoceptive fear learning to mild breathlessness as a laboratory model for unexpected panic attacks

    OpenAIRE

    Pappens, Meike; Vandenbossche, Evelien; Van den Bergh, Omer; Van Diest, Ilse

    2015-01-01

    Fear learning is thought to play an important role in panic disorder. Benign interoceptive sensations can become predictors (conditioned stimuli – CSs) of massive fear when experienced in the context of an initial panic attack (unconditioned stimulus – US). The mere encounter of these CSs on a later moment can induce anxiety and fear, and precipitate a new panic attack. It has been suggested that fear learning to interoceptive cues would result in unpredictable panic. The present study aimed ...

  6. Interoceptive fear learning to mild breathlessness as a laboratory model for unexpected panic attacks

    OpenAIRE

    Meike ePappens; Omer eVan Den Bergh; Evelien eVandebossche; Ilse eVan Diest

    2015-01-01

    Fear learning is thought to play an important role in panic disorder. Benign interoceptive sensations can become predictors (conditioned stimuli - CSs) of massive fear when experienced in the context of an initial panic attack (unconditioned stimulus – US). The mere encounter of these CSs on a later moment can induce anxiety and fear, and precipitate a new panic attack. It has been suggested that fear learning to interoceptive cues would result in unpredictable panic. The present study aimed ...

  7. Inhibition of vicariously learned fear in children using positive modeling and prior exposure

    OpenAIRE

    Askew, Chris; Reynolds, Gemma; Fielding-Smith, Sarah; Field, Andy P.

    2016-01-01

    One of the challenges to conditioning models of fear acquisition is to explain how different individuals can experience similar learning events and only some of them subsequently develop fear. Understanding factors moderating the impact of learning events on fear acquisition is key to understanding the etiology and prevention of fear in childhood. This study investigates these moderators in the context of vicarious (observational) learning. Two experiments tested predictions that the acquisit...

  8. ERK-Associated Changes of AP-1 Proteins During Fear Extinction

    OpenAIRE

    Guedea, Anita L.; Schrick, Christina; Guzman, Yomayra F.; Leaderbrand, Katie; Jovasevic, Vladimir; Corcoran, Kevin A.; Tronson, Natalie C; Radulovic, Jelena

    2011-01-01

    Extensive research has unraveled the molecular basis of learning processes underlying contextual fear conditioning, but the mechanisms of fear extinction remain less known. Contextual fear extinction occurs when an aversive stimulus that initially caused fear is no longer present and depends on the activation of the extracellular signal-regulated kinase (ERK), among other molecules. Here we investigated how ERK signaling triggered by extinction affects its downstream targets belonging to the ...

  9. Understanding animal fears: a comparison of the cognitive vulnerability and harm-looming models

    Directory of Open Access Journals (Sweden)

    Armfield Jason M

    2007-12-01

    Full Text Available Abstract Background The Cognitive Vulnerability Model holds that both clinical and sub-clinical manifestations of animal fears are a result of how an animal is perceived, and can be used to explain both individual differences in fear acquisition and the uneven distribution of fears in the population. This study looked at the association between fear of a number of animals and perceptions of the animals as uncontrollable, unpredictable, dangerous and disgusting. Also assessed were the perceived loomingness, prior familiarity, and negative evaluation of the animals as well as possible conditioning experiences. Methods 162 first-year University students rated their fear and perceptions of four high-fear and four low-fear animals. Results Perceptions of the animals as dangerous, disgusting and uncontrollable were significantly associated with fear of both high- and low-fear animals while perceptions of unpredictability were significantly associated with fear of high-fear animals. Conditioning experiences were unrelated to fear of any animals. In multiple regression analyses, loomingness did not account for a significant amount of the variance in fear beyond that accounted for by the cognitive vulnerability variables. However, the vulnerability variables accounted for between 20% and 51% of the variance in all animals fears beyond that accounted for by perceptions of the animals as looming. Perceptions of dangerousness, uncontrollability and unpredictability were highly predictive of the uneven distribution of animal fears. Conclusion This study provides support for the Cognitive Vulnerability Model of the etiology of specific fears and phobias and brings into question the utility of the harm-looming model in explaining animal fear.

  10. Fear of holes.

    Science.gov (United States)

    Cole, Geoff G; Wilkins, Arnold J

    2013-10-01

    Phobias are usually described as irrational and persistent fears of certain objects or situations, and causes of such fears are difficult to identify. We describe an unusual but common phobia (trypophobia), hitherto unreported in the scientific literature, in which sufferers are averse to images of holes. We performed a spectral analysis on a variety of images that induce trypophobia and found that the stimuli had a spectral composition typically associated with uncomfortable visual images, namely, high-contrast energy at midrange spatial frequencies. Critically, we found that a range of potentially dangerous animals also possess this spectral characteristic. We argue that although sufferers are not conscious of the association, the phobia arises in part because the inducing stimuli share basic visual characteristics with dangerous organisms, characteristics that are low level and easily computed, and therefore facilitate a rapid nonconscious response. PMID:23982244

  11. Classical Mechanics

    OpenAIRE

    Gallavotti, Giovanni

    1999-01-01

    This is the English version of a friendly graduate course on Classical Mechanics, containing about 80% of the material I covered during the January-June 1999 semester at IFUG in the Mexican city of Leon. For the Spanish version, see physics/9906066

  12. Investigation on reactivity of non-classical carbenes with sterically hindered Lewis acid, B(C6F5)3 under inert and open conditions

    Indian Academy of Sciences (India)

    Arunabha Thakur; Pavan K Vardhanapu; Gonela Vijaykumar; Sushil Ranjan Bhatta

    2016-04-01

    Reactions of B(C6F5)3 with abnormal N-heterocyclic carbene (NHC), L1 and cyclic (alkyl)(amino) carbene (AAC), L2 in the presence of moisture as well as in its absence, have been investigated in toluene. Reaction of NHC with 1 equivalent of B(C6F5)3 under inert condition produced classical Lewis acid-base adduct, [L1.B(C6F5)3], 1. Further, probing the same reaction with cyclic (alkyl)(amino) carbene (AAC), having different electronic property, led to the isolation of [L2.B(C6F5)3], 2 under inert condition. Interestingly, reaction of NHC or AAC with 1 equivalent of B(C6F5)3 in the presence of moisture resulted in water splitting leading to the formation of [L1-H][(OH)B(C6F5)3], 3 and [L2-H][(OH)B(C6F5)3, 4. All these compounds (1-4) were characterized in solution by 1H, 13C, 19F and 11B NMR spectroscopy. Additionally, the solid-state structures were unambiguously established by crystallographic analysis of compounds 1-4.

  13. Ion mobility spectrometry versus classical physico-chemical analysis for assessing the shelf life of extra virgin olive oil according to container type and storage conditions.

    Science.gov (United States)

    Garrido-Delgado, Rocío; Dobao-Prieto, M Mar; Arce, Lourdes; Aguilar, Joaquín; Cumplido, José L; Valcárcel, Miguel

    2015-03-01

    An experimental study was conducted to assess the stability of a single-variety (Arbequina) extra virgin olive oil (EVOO) as a function of container type and storage conditions over a period of 11 months. EVOO quality was assessed by using ion mobility spectrometry (IMS), which provides increased simplicity, expeditiousness, and relative economy. The results were compared with the ones obtained by using the official method based on classical physico-chemical analysis. Bag-in-box, metal, dark glass, clear glass, and polyethylene terephthalate containers holding EVOO were opened on a periodic basis for sampling to simulate domestic use; in parallel, other containers were kept closed until analysis to simulate the storage conditions on market shelves. The results of the physico-chemical and instrumental analyses led to similar conclusions. Thus, samples packaged in bag-in-box containers preserved oil quality for 11 months, better than other container types. The HS-GC-IMS results confirm that 2-heptenal and 1-penten-3-one are two accurate markers of EVOO quality. PMID:25645180

  14. Molecular mechanisms of D-cycloserine in facilitating fear extinction: insights from RNAseq.

    Science.gov (United States)

    Malan-Müller, Stefanie; Fairbairn, Lorren; Daniels, Willie M U; Dashti, Mahjoubeh Jalali Sefid; Oakeley, Edward J; Altorfer, Marc; Kidd, Martin; Seedat, Soraya; Gamieldien, Junaid; Hemmings, Sîan Megan Joanna

    2016-02-01

    D-cycloserine (DCS) has been shown to be effective in facilitating fear extinction in animal and human studies, however the precise mechanisms whereby the co-administration of DCS and behavioural fear extinction reduce fear are still unclear. This study investigated the molecular mechanisms of intrahippocampally administered D-cycloserine in facilitating fear extinction in a contextual fear conditioning animal model. Male Sprague Dawley rats (n = 120) were grouped into four experimental groups (n = 30) based on fear conditioning and intrahippocampal administration of either DCS or saline. The light/dark avoidance test was used to differentiate maladapted (MA) (anxious) from well-adapted (WA) (not anxious) subgroups. RNA extracted from the left dorsal hippocampus was used for RNA sequencing and gene expression data was compared between six fear-conditioned + saline MA (FEAR + SALINE MA) and six fear-conditioned + DCS WA (FEAR + DCS WA) animals. Of the 424 significantly downregulated and 25 significantly upregulated genes identified in the FEAR + DCS WA group compared to the FEAR + SALINE MA group, 121 downregulated and nine upregulated genes were predicted to be relevant to fear conditioning and anxiety and stress-related disorders. The majority of downregulated genes transcribed immune, proinflammatory and oxidative stress systems molecules. These molecules mediate neuroinflammation and cause neuronal damage. DCS also regulated genes involved in learning and memory processes, and genes associated with anxiety, stress-related disorders and co-occurring diseases (e.g., cardiovascular diseases, digestive system diseases and nervous system diseases). Identifying the molecular underpinnings of DCS-mediated fear extinction brings us closer to understanding the process of fear extinction. PMID:26400817

  15. Cognitive vulnerability and dental fear

    Directory of Open Access Journals (Sweden)

    Spencer A John

    2008-01-01

    Full Text Available Abstract Background The Cognitive Vulnerability Model proposes that perceptions of certain characteristics of a situation are critical determinants of fear. Although the model is applicable to all animal, natural environment and situational fears, it has not yet been applied specifically to dental fear. This study therefore aimed to examine the association between dental fear and perceptions of dental visits as uncontrollable, unpredictable and dangerous. Methods The study used a clustered, stratified national sample of Australians aged 15 years and over. All participants were asked in a telephone interview survey to indicate their level of dental fear. Participants who received an oral examination were subsequently provided with a self-complete questionnaire in which they rated their perceptions of uncontrollability, unpredictability and dangerousness associated with dental visiting. Results 3937 participants were recruited. Each of the three vulnerability-related perceptions was strongly associated with the prevalence of high dental fear. In a logistic regression analysis, uncontrollability and dangerousness perceptions were significantly associated with high dental fear after controlling for age and sex. However, unpredictability perceptions did not have a statistically significant independent association with dental fear after controlling for all other variables. Conclusion Results are mostly consistent with the Cognitive Vulnerability Model of the etiology of fear, with perceptions of uncontrollability, unpredictability and dangerousness each showing a strong bivariate relationship with high dental fear prevalence. However, more extensive measures of vulnerability perceptions would be valuable in future investigations.

  16. Inhibition of Rac1 Activity in the Hippocampus Impairs the Forgetting of Contextual Fear Memory.

    Science.gov (United States)

    Jiang, Lizhu; Mao, Rongrong; Zhou, Qixin; Yang, Yuexiong; Cao, Jun; Ding, Yuqiang; Yang, Yuan; Zhang, Xia; Li, Lingjiang; Xu, Lin

    2016-03-01

    Fear is crucial for survival, whereas hypermnesia of fear can be detrimental. Inhibition of the Rac GTPase is recently reported to impair the forgetting of initially acquired memory in Drosophila. Here, we investigated whether inhibition of Rac1 activity in rat hippocampus could contribute to the hypermnesia of contextual fear. We found that spaced but not massed training of contextual fear conditioning caused inhibition of Rac1 activity in the hippocampus and heightened contextual fear. Furthermore, intrahippocampal injection of the Rac1 inhibitor NSC23766 heightened contextual fear in massed training, while Rac1 activator CN04-A weakened contextual fear in spaced training rats. Our study firstly demonstrates that contextual fear memory in rats is actively regulated by Rac1 activity in the hippocampus, which suggests that the forgetting impairment of traumatic events in posttraumatic stress disorder may be contributed to the pathological inhibition of Rac1 activity in the hippocampus. PMID:25613020

  17. Cannabinoid facilitation of fear extinction memory recall in humans

    OpenAIRE

    Rabinak, Christine A.; Angstadt, Mike; Sripada, Chandra S.; James L. Abelson; Liberzon, Israel; Milad, Mohammed R; Phan, K. Luan

    2012-01-01

    A first-line approach to treat anxiety disorders is exposure-based therapy, which relies on extinction processes such as repeatedly exposing the patient to stimuli (conditioned stimuli; CS) associated with the traumatic, fear-related memory. However, a significant number of patients fail to maintain their gains, partly attributed to the fact that this inhibitory learning and its maintenance is temporary and conditioned fear responses can return. Animal studies have shown that activation of th...

  18. Animal models of fear relapse.

    Science.gov (United States)

    Goode, Travis D; Maren, Stephen

    2014-01-01

    Whereas fear memories are rapidly acquired and enduring over time, extinction memories are slow to form and are susceptible to disruption. Consequently, behavioral therapies that involve extinction learning (e.g., exposure therapy) often produce only temporary suppression of fear and anxiety. This review focuses on the factors that are known to influence the relapse of extinguished fear. Several phenomena associated with the return of fear after extinction are discussed, including renewal, spontaneous recovery, reacquisition, and reinstatement. Additionally, this review describes recent work, which has focused on the role of psychological stress in the relapse of extinguished fear. Recent developments in behavioral and pharmacological research are examined in light of treatment of pathological fear in humans. PMID:25225304

  19. 860 MHz微波辐射对小鼠场景性条件恐惧的影响%Effects of 860 MHz microwave on context conditioned fear in mice

    Institute of Scientific and Technical Information of China (English)

    吴冰; 胡波; 隋建峰

    2010-01-01

    Objective To investigate the effects of 860MHz microwave on the formation and extinction of context conditioned fear in mice. Methods The mice were exposed to 860MHz continuous microwave ( power density were 380 μW/cm2 or 550 μW/cm2, respectively) for 30 min or 2 h, which then were divided in to 5 groups.Each group consisted of 15 animals. Footshocks were used to induce context conditioned fear by 75 voltages. The frequency and time of freezing after irradiation were investigated. Results When 24 h after foot shocking, the values of freezing time: control group was 2.31 ±4. 17 , two groups of the microwave irradiation 2 h were 3.93 ±6.99 and 2.47 ± 3.34, the Nemenyi test results (P = 0.004): control group was 32.63333, while two groups of the microwave irradiation 2 h were 52.46667 and 39.76667; and the values of freezing frequency: control group was 0.73 ± 1.16 , two groups of the microwave irradiation 2 h were 0.86 ± 1.41 and 1.07 ± 1.16, the Nemenyi test results of (P=0. 014): control group was 33. 26667, while two groups of the microwave irradiation 2 h were 50. 76667 and 40.90000. Conclusion The mice receiving relatively longer period of microwave irradiation showed more stable memory of the context conditioned fear.%目的 研究860 MHz微波辐射对小鼠场景性条件恐惧(context conditioned fear)形成和消退的影响.方法 用频率为860 MHz、功率密度分别为380μW/cm2、550μW/cm2的微波辐照小鼠.辐照时间分别设定为30min和2h,因此共分成5组,每组15只动物.在暗箱内用75 V电压电击动物足部的方法 产生与之关联的场景性条件恐惧,而后观察辐照后小鼠在特定时间内出现僵立(Freezing)的时间和次数.结果 足部电击后24h时的僵立时间的值:对照组为(2.13±4.17)s,微波辐照2h的两个组分别为(3.93±6.99)s和(2.47±3.34)s,Nemenyi的检验(P=0.004)结果 :对照组为32.63333,而微波辐照2h的两个组分别为52.46667和39.76667;僵立

  20. Prenatal immune challenge in rats: effects of polyinosinic-polycytidylic acid on spatial learning, prepulse inhibition, conditioned fear, and responses to MK-801 and amphetamine.

    Science.gov (United States)

    Vorhees, Charles V; Graham, Devon L; Braun, Amanda A; Schaefer, Tori L; Skelton, Matthew R; Richtand, Neil M; Williams, Michael T

    2015-01-01

    Prenatal maternal immune activation increases risk for schizophrenia and/or autism. Previous data suggest that maternal weight change in response to the immune activator polyinosinic-polycytidylic (Poly IC) in rats influences the severity of effect in the offspring as does the exposure period. We treated gravid Sprague-Dawley rats from E14 to 18 with 8mg/kg/day Poly IC or saline. The Poly IC group was divided into those that gained the least weight or lost (Poly IC (L)) and those that gained the most (Poly IC (H)) weight. There were no effects of Poly IC on anxiety (elevated zero-maze, open-field, object burying), or Morris water maze cued learning or working memory or Cincinnati water maze egocentric learning. The Poly IC (H) group males had decreased acoustic startle whereas Poly IC (L) females had reduced startle and increased PPI. Poly IC offspring showed exaggerated hyperactivity in response to amphetamine (primarily in the Poly IC (H) group) and attenuated hyperactivity in response to MK-801 challenge (primarily in the Poly IC (L) group). Poly IC (L) males showed reduced cued conditioned freezing; both sexes showed less time in the dark in a light-dark test, and the Poly IC groups showed impaired Morris water maze hidden platform acquisition and probe performance. The data demonstrate that offspring from the most affected dams were more affected than those from less reactive dams indicating that degree of maternal immune activation predicts severity of effects on offspring behavior. PMID:25450663

  1. Modulation of NR2B-regulated contextual fear in the hippocampus by the tissue plasminogen activator system

    OpenAIRE

    Norris, Erin H.; Strickland, Sidney

    2007-01-01

    Contextual fear conditioning is regulated by the hippocampus, and NR2B, a subunit of the NMDA receptor (NR), is involved in this process. We show that acute stress modulates tissue plasminogen activator (tPA) activity in the hippocampus by inducing expression of its inhibitor, plasminogen activator inhibitor-1. Acute stress increases NR2B expression and ERK1/2 phosphorylation, a classical marker of postsynaptic plasticity, in the hippocampus. tPA forms a complex with NR2B and is necessary for...

  2. Classical entropy generation analysis in cooled homogenous and functionally graded material slabs with variation of internal heat generation with temperature, and convective–radiative boundary conditions

    International Nuclear Information System (INIS)

    This article investigates the classical entropy generation in cooled slabs. Two types of materials are assumed for the slab: homogeneous material and FGM (functionally graded material). For the homogeneous material, the thermal conductivity is assumed to be a linear function of temperature, while for the FGM slab the thermal conductivity is modeled to vary in accordance with the rule of mixtures. The boundary conditions are assumed to be convective and radiative concurrently, and the internal heat generation of the slab is a linear function of temperature. Using the DTM (differential transformation method) and resultant temperature fields from the DTM, the local and total entropy generation rates within slabs are derived. The effects of physically applicable parameters such as the thermal conductivity parameter for the homogenous slab, β, the thermal conductivity parameter for the FGM slab, γ, gradient index, j, internal heat generation parameter, Q, Biot number at the right side, Nc2, conduction–radiation parameter, Nr2, dimensionless convection sink temperature, δ, and dimensionless radiation sink temperature, η, on the local and total entropy generation rates are illustrated and explained. The results demonstrate that considering temperature- or coordinate-dependent thermal conductivity and radiation heat transfer at both sides of the slab have great effects on the entropy generation. - Highlights: • The paper investigates entropy generation in a slab due to heat generation and convective–radiative boundary conditions. • Both homogeneous material and FGM (functionally graded material) were considered. • The calculations are carried out using the differential transformation method which is a well-tested analytical technique

  3. Exploring Fear: Rousseau, Dewey, and Freire on Fear and Learning

    Science.gov (United States)

    English, Andrea; Stengel, Barbara

    2010-01-01

    Fear is not the first feature of educational experience associated with the best-known progressive educational theorists--Jean-Jacques Rousseau, John Dewey, and Paolo Freire. But each of these important thinkers did, in fact, have something substantive to say about how fear functions in the processes of learning and growth. Andrea English and…

  4. Impaired fear extinction learning and cortico-amygdala circuit abnormalities in a common genetic mouse strain

    OpenAIRE

    Hefner, Kathryn; Whittle, Nigel; Juhasz, Jaynann; Norcross, Maxine; Karlsson, Rose-Marie; Saksida, Lisa M.; Bussey, Timothy J.; Singewald, Nicolas; Holmes, Andrew

    2008-01-01

    Fear extinction is a form of new learning that results in the inhibition of conditioned fear. Trait deficits in fear extinction are a risk factor for anxiety disorders. There are few examples of naturally-occurring animal models of impaired extinction. The present study compared fear extinction in a panel of inbred mouse strains. This strain survey revealed an impairment in fear extinction in 129/SvImJ (129S1). The phenotypic specificity of this deficit was evaluated by comparing 129S1 and C5...

  5. The formation and extinction of fear memory in tree shrews

    OpenAIRE

    Shujiang eShang; Cong eWang; Chengbin eGuo; Xu eHuang; Liecheng eWang; Chen eZhang

    2015-01-01

    Fear is an emotion that is well studied due to its importance for animal survival. Experimental animals, such as rats and mice, have been widely used to model fear. However, higher animals such as nonhuman primates have rarely been used to study fear due to ethical issues and high costs. Tree shrews are small mammals that are closely related to primates; they have been used to model human-related psychosocial conditions such as stress and alcohol tolerance. Here, we describe an experimental p...

  6. Understanding amygdala responsiveness to fearful expressions through the lens of psychopathy and altruism.

    Science.gov (United States)

    Marsh, Abigail A

    2016-06-01

    Because the face is the central focus of human social interactions, emotional facial expressions provide a unique window into the emotional lives of others. They play a particularly important role in fostering empathy, which entails understanding and responding to others' emotions, especially distress-related emotions such as fear. This Review considers how fearful facial as well as vocal and postural expressions are interpreted, with an emphasis on the role of the amygdala. The amygdala may be best known for its role in the acquisition and expression of conditioned fear, but it also supports the perception and recognition of others' fear. Various explanations have been supplied for the amygdala's role in interpreting and responding to fearful expressions. They include theories that amygdala responses to fearful expressions 1) reflect heightened vigilance in response to uncertain danger, 2) promote heightened attention to the eye region of faces, 3) represent a response to an unconditioned aversive stimulus, or 4) reflect the generation of an empathic fear response. Among these, only empathic fear explains why amygdala lesions would impair fear recognition across modalities. Supporting the possibility of a link between fundamental empathic processes and amygdala responses to fear is evidence that impaired fear recognition in psychopathic individuals results from amygdala dysfunction, whereas enhanced fear recognition in altruistic individuals results from enhanced amygdala function. Empathic concern and caring behaviors may be fostered by sensitivity to signs of acute distress in others, which relies on intact functioning of the amygdala. PMID:26366635

  7. Hidden sources of joy, fear, and sadness

    DEFF Research Database (Denmark)

    Bogert, Brigitte; Numminen-Kontti, Taru; Gold, Benjamin;

    2016-01-01

    to be associated with the cognitive processing of music and emotion recognition and regulation. Moreover, happiness in music was associated with activity in the bilateral auditory cortex, left parahippocampal gyrus, and supplementary motor area, whereas the negative emotions of sadness and fear corresponded......Music is often used to regulate emotions and mood. Typically, music conveys and induces emotions even when one does not attend to them. Studies on the neural substrates of musical emotions have, however, only examined brain activity when subjects have focused on the emotional content of the music....... Here we address with functional magnetic resonance imaging (fMRI) the neural processing of happy, sad, and fearful music with a paradigm in which 56 subjects were instructed to either classify the emotions (explicit condition) or pay attention to the number of instruments playing (implicit condition...

  8. Neural correlates of individual differences in fear learning.

    Science.gov (United States)

    MacNamara, Annmarie; Rabinak, Christine A; Fitzgerald, Daniel A; Zhou, Xiaohong Joe; Shankman, Stewart A; Milad, Mohammed R; Phan, K Luan

    2015-01-01

    Variability in fear conditionability is common, and clarity regarding the neural regions responsible for individual differences in fear conditionability could uncover brain-based biomarkers of resilience or vulnerability to trauma-based psychopathologies (e.g., post-traumatic stress disorder). In recent years, neuroimaging work has yielded a detailed understanding of the neural mechanisms underlying fear conditioning common across participants, however only a minority of studies have investigated the brain basis of inter-individual variation in fear learning. Moreover, the majority of these studies have employed small sample sizes (mean n=17; range n=5-27) and all have failed to meet the minimum recommended sample size for functional magnetic resonance imaging (fMRI) studies of individual differences. Here, using fMRI, we analyzed blood-oxygenation level dependent (BOLD) response recorded simultaneously with skin conductance response (SCR) and ratings of unconditioned stimulus (US) expectancy in 49 participants undergoing Pavlovian fear conditioning. On average, participants became conditioned to the conditioned stimulus (CS+; higher US expectancy ratings and SCR for the CS+ compared to the unpaired conditioned stimulus, CS-); the CS+ also robustly increased activation in the bilateral insula. Amygdala activation was revealed from a regression analysis that incorporated individual differences in fear conditionability (i.e., a between-subjects regressor of mean CS+>CS- SCR). By replicating results observed using much smaller sample sizes, the results confirm that variation in amygdala reactivity covaries with individual differences in fear conditionability. The link between behavior (SCR) and brain (amygdala reactivity) may be a putative endophenotype for the acquisition of fear memories. PMID:25819422

  9. The learning of fear extinction.

    Science.gov (United States)

    Furini, Cristiane; Myskiw, Jociane; Izquierdo, Ivan

    2014-11-01

    Recent work on the extinction of fear-motivated learning places emphasis on its putative circuitry and on its modulation. Extinction is the learned inhibition of retrieval of previously acquired responses. Fear extinction is used as a major component of exposure therapy in the treatment of fear memories such as those of the posttraumatic stress disorder (PTSD). It is initiated and maintained by interactions between the hippocampus, basolateral amygdala and ventromedial prefrontal cortex, which involve feedback regulation of the latter by the other two areas. Fear extinction depends on NMDA receptor activation. It is positively modulated by d-serine acting on the glycine site of NMDA receptors and blocked by AP5 (2-amino-5-phosphono propionate) in the three structures. In addition, histamine acting on H2 receptors and endocannabinoids acting on CB1 receptors in the three brain areas mentioned, and muscarinic cholinergic fibers from the medial septum to hippocampal CA1 positively modulate fear extinction. Importantly, fear extinction can be made state-dependent on circulating epinephrine, which may play a role in situations of stress. Exposure to a novel experience can strongly enhance the consolidation of fear extinction through a synaptic tagging and capture mechanism; this may be useful in the therapy of states caused by fear memory like PTSD. PMID:25452113

  10. Heritability of fear: Ukrainian experience

    Directory of Open Access Journals (Sweden)

    O.V. Filiptsova

    2014-10-01

    Conclusions: The conducted research demonstrated genetic component presence for nine types of fear – psychic disorder development, complications in personal life, making responsible decisions, senility, closed spaces, sexual dysfunction, suicide commission, speaking in public, and aggressive behavior possibility to relatives. It helps to consider these fear perspectives for further molecular-genetic analysis in Ukraine.

  11. Classical tachyons

    International Nuclear Information System (INIS)

    A review of tachyons, with particular attention to their classical theory, is presented. The extension of Special Relativity to tachyons in two dimensional is first presented, an elegant model-theory which allows a better understanding also of ordinary physics. Then, the results are extended to the four-dimensional case (particular on tachyon mechanics) that can be derived without assuming the existence of Super-luminal reference-frames. Localizability and the unexpected apparent shape of tachyonic objects are discussed, and it is shown (on the basis of tachyon kinematics) how to solve the common causal paradoxes. In connection with General Relativity, particularly the problem of the apparent superluminal expansions in astrophysics is reviewed. The problem (still open) of the extension of relativitic theories to tachyons in four dimensions is tackled, and the electromagnetic theory of tachyons, a topic that can be relevant also for the experimental side, is reviewed. (Author)

  12. Extinction in multiple virtual reality contexts diminishes fear reinstatement in humans.

    Science.gov (United States)

    Dunsmoor, Joseph E; Ahs, Fredrik; Zielinski, David J; LaBar, Kevin S

    2014-09-01

    Although conditioned fear can be effectively extinguished by unreinforced exposure to a threat cue, fear responses tend to return when the cue is encountered some time after extinction (spontaneous recovery), in a novel environment (renewal), or following presentation of an aversive stimulus (reinstatement). As extinction represents a context-dependent form of new learning, one possible strategy to circumvent the return of fear is to conduct extinction across several environments. Here, we tested the effectiveness of multiple context extinction in a two-day fear conditioning experiment using 3-D virtual reality technology to create immersive, ecologically-valid context changes. Fear-potentiated startle served as the dependent measure. All three experimental groups initially acquired fear in a single context. A multiple extinction group then underwent extinction in three contexts, while a second group underwent extinction in the acquisition context and a third group underwent extinction in a single different context. All groups returned 24h later to test for return of fear in the extinction context (spontaneous recovery) and a novel context (renewal and reinstatement/test). Extinction in multiple contexts attenuated reinstatement of fear but did not reduce spontaneous recovery. Results from fear renewal were tendential. Our findings suggest that multi-context extinction can reduce fear relapse following an aversive event--an event that often induces return of fear in real-world settings--and provides empirical support for conducting exposure-based clinical treatments across a variety of environments. PMID:24583374

  13. EXISTENTIAL FEAR AS ONTOLOGICALLY BACKGROUND OF MEDIOCRITY

    OpenAIRE

    Гіоргадзе, Галина Василівна

    2016-01-01

    The article deals with the phenomenon of fear in terms of the influence of its varieties (fear as a biological defense mechanism, fear as a psychological phenomenon, the varieties of existential fears) on human life and the possibility of creative self. It is determined the protective function of fear, its inhibitory effect on personal development and the limit effect of domestic and social freedom. Particular attention is paid to the analysis of existential fear as a (mostly unconscious) "br...

  14. Single prolonged stress disrupts retention of extinguished fear in rats

    OpenAIRE

    Knox, Dayan; George, Sophie A.; Christopher J Fitzpatrick; Rabinak, Christine A.; Maren, Stephen; Liberzon, Israel

    2012-01-01

    Clinical research has linked post-traumatic stress disorder (PTSD) with deficits in fear extinction. However, it is not clear whether these deficits result from stress-related changes in the acquisition or retention of extinction or in the regulation of extinction memories by context, for example. In this study, we used the single prolonged stress (SPS) animal model of PTSD and fear conditioning procedures to examine the effects of prior traumatic stress on the acquisition, retention, and con...

  15. Reduced fear expression after lesions of the ventral hippocampus

    OpenAIRE

    Kjelstrup, Kirsten G.; Tuvnes, Frode A.; Steffenach, Hill-Aina; Murison, Robert; Moser, Edvard I; Moser, May-Britt

    2002-01-01

    The hippocampus has a critical role in several fundamental memory operations, including the conditioning of fear to contextual information. We show that the hippocampus is necessary also for unconditioned fear, and that the involved circuitry is at the ventral pole of the hippocampus. Rats with selective hippocampal lesions failed to avoid open arms in an elevated plus-maze and had decreased neuroendocrine stress responses during confinement to a brightly lit chamber. These effects were repro...

  16. Inhibition and enhancement of contextual fear memory destabilization

    OpenAIRE

    Lee, Jonathan L. C.; Charlotte eFlavell

    2014-01-01

    The reactivation of a memory can result in its destabilization, necessitating a process of memory reconsolidation to maintain its persistence. Here we show that the destabilization of a contextual fear memory is potentiated by the cannabinoid CB1 receptor agonist ACEA. Co-infusion of ACEA and the IKK inhibitor sulfasalazine into the dorsal hippocampus impaired contextual fear memory reconsolidation. This observation was achieved under behavioural conditions that, by themselves, did not result...

  17. Caloric restriction enhances fear extinction learning in mice.

    Science.gov (United States)

    Riddle, Megan C; McKenna, Morgan C; Yoon, Yone J; Pattwell, Siobhan S; Santos, Patricia Mae G; Casey, B J; Glatt, Charles E

    2013-05-01

    Fear extinction learning, the ability to reassess a learned cue of danger as safe when it no longer predicts aversive events, is often dysregulated in anxiety disorders. Selective serotonin reuptake inhibitors (SSRI's) enhance neural plasticity and their ability to enhance fear extinction learning may explain their anxiolytic properties. Caloric restriction (CR) has SSRI-like effects on neural plasticity and anxiety-related behavior. We implemented CR in mice to determine its effects on conditioned-fear responses. Wild type and serotonin transporter (SERT) knockout mice underwent CR for 7 days leading to significant weight loss. Mice were then tested for cued fear learning and anxiety-related behavior. CR markedly enhanced fear extinction learning and its retention in adolescent female mice, and adults of both sexes. These effects of CR were absent in SERT knockout mice. Moreover, CR phenocopied behavioral and molecular effects of chronic fluoxetine, but there was no additive effect of CR in fluoxetine-treated mice. These results demonstrate that CR enhances fear extinction learning through a SERT-dependent mechanism. These results may have implications for eating disorders such as anorexia nervosa (AN), in which there is a high prevalence of anxiety before the onset of dietary restriction and support proposals that in AN, CR is a motivated effort to control dysregulated fear responses and elevated anxiety. PMID:23303073

  18. Classical and quantum effective theories

    CERN Document Server

    Polonyi, Janos

    2014-01-01

    A generalization of the action principle of classical mechanics, motivated by the Closed Time Path (CTP) scheme of quantum field theory, is presented to deal with initial condition problems and dissipative forces. The similarities of the classical and the quantum cases are underlined. In particular, effective interactions which describe classical dissipative forces represent the system-environment entanglement. The relation between the traditional effective theories and their CTP extension is briefly discussed and few qualitative examples are mentioned.

  19. The role of the medial prefrontal cortex in trace fear extinction

    OpenAIRE

    Kwapis, Janine L.; Jarome, Timothy J.; Fred J Helmstetter

    2015-01-01

    The extinction of delay fear conditioning relies on a neural circuit that has received much attention and is relatively well defined. Whether this established circuit also supports the extinction of more complex associations, however, is unclear. Trace fear conditioning is a better model of complex relational learning, yet the circuit that supports extinction of this memory has received very little attention. Recent research has indicated that trace fear extinction requires a different neural...

  20. Natural amyloid-β oligomers acutely impair the formation of a contextual fear memory in mice.

    Directory of Open Access Journals (Sweden)

    Kara A Kittelberger

    Full Text Available Memory loss is one of the hallmark symptoms of Alzheimer's disease (AD. It has been proposed that soluble amyloid-beta (Abeta oligomers acutely impair neuronal function and thereby memory. We here report that natural Abeta oligomers acutely impair contextual fear memory in mice. A natural Abeta oligomer solution containing Abeta monomers, dimers, trimers, and tetramers was derived from the conditioned medium of 7PA2 cells, a cell line that expresses human amyloid precursor protein containing the Val717Phe familial AD mutation. As a control we used 7PA2 conditioned medium from which Abeta oligomers were removed through immunodepletion. Separate groups of mice were injected with Abeta and control solutions through a cannula into the lateral brain ventricle, and subjected to fear conditioning using two tone-shock pairings. One day after fear conditioning, mice were tested for contextual fear memory and tone fear memory in separate retrieval trials. Three experiments were performed. For experiment 1, mice were injected three times: 1 hour before and 3 hours after fear conditioning, and 1 hour before context retrieval. For experiments 2 and 3, mice were injected a single time at 1 hour and 2 hours before fear conditioning respectively. In all three experiments there was no effect on tone fear memory. Injection of Abeta 1 hour before fear conditioning, but not 2 hours before fear conditioning, impaired the formation of a contextual fear memory. In future studies, the acute effect of natural Abeta oligomers on contextual fear memory can be used to identify potential mechanisms and treatments of AD associated memory loss.

  1. Minocycline attenuates interferon-α-induced impairments in rat fear extinction

    OpenAIRE

    Bi, Qiang; Shi, Lijuan; Yang, Pingting; Wang, Jianing; Qin, Ling

    2016-01-01

    Background Extinction of conditioned fear is an important brain function for animals to adapt to a new environment. Accumulating evidence suggests that innate immune cytokines are involved in the pathology of psychotic disorders. However, the involvement of cytokines in fear dysregulation remains less investigated. In the present study, we investigated how interferon (IFN)-α disrupts the extinction of conditioned fear and propose an approach to rescue IFN-α-induced neurologic impairment. Meth...

  2. Fear Extinction to an Out-Group Face: The Role of Target Gender

    OpenAIRE

    Navarrete, Carlos D.; Thomsen, Lotte; Olsson, Andreas; Mendes, Wendy; Sidanius, James; Ho, Arnold

    2009-01-01

    Conditioning studies on humans and other primates show that fear responses acquired toward danger-relevant stimuli, such as snakes, resist extinction, whereas responses toward danger-irrelevant stimuli, such as birds, are more readily extinguished. Similar evolved biases may extend to human groups, as recent research demonstrates that a conditioned fear response to faces of persons of a social out-group resists extinction, whereas fear toward a social in-group is more readily extinguished. He...

  3. Ventromedial prefrontal cortex activity and rapid eye movement sleep are associated with subsequent fear expression in human subjects.

    Science.gov (United States)

    Spoormaker, V I; Gvozdanovic, G A; Sämann, P G; Czisch, M

    2014-05-01

    In humans, activity patterns in the ventromedial prefrontal cortex (vmPFC) have been found to be predictive of subsequent fear memory consolidation. Pioneering work in rodents has further shown that vmPFC-amygdala theta synchronization is correlated with fear memory consolidation. We aimed to evaluate whether vmPFC activity during fear conditioning is (1) correlated with fear expression the subsequent day and whether (2) this relationship is mediated by rapid eye movement (REM) sleep. We analyzed data from 17 young healthy subjects undergoing a fear conditioning task, followed by a fear extinction task 24 h later, both recorded with simultaneous skin conductance response (SCR) and functional magnetic resonance imaging measurements, with a polysomnographically recorded night sleep in between. Our results showed a correlation between vmPFC activity during fear conditioning and subsequent REM sleep amount, as well as between REM sleep amount and SCR to the conditioned stimulus 24 h later. Moreover, we observed a significant correlation between vmPFC activity during fear conditioning and SCR responses during extinction, which was no longer significant after controlling for REM sleep amount. vmPFC activity during fear conditioning was further correlated with sleep latency. Interestingly, hippocampus activity during fear conditioning was correlated with stage 2 and stage 4 sleep amount. Our results provide preliminary evidence that the relationship between REM sleep and fear conditioning and extinction observed in rodents can be modeled in healthy human subjects, highlighting an interrelated set of potentially relevant trait markers. PMID:24452776

  4. Fear extinction causes target-specific remodeling of perisomatic inhibitory synapses.

    Science.gov (United States)

    Trouche, Stéphanie; Sasaki, Jennifer M; Tu, Tiffany; Reijmers, Leon G

    2013-11-20

    A more complete understanding of how fear extinction alters neuronal activity and connectivity within fear circuits may aid in the development of strategies to treat human fear disorders. Using a c-fos-based transgenic mouse, we found that contextual fear extinction silenced basal amygdala (BA) excitatory neurons that had been previously activated during fear conditioning. We hypothesized that the silencing of BA fear neurons was caused by an action of extinction on BA inhibitory synapses. In support of this hypothesis, we found extinction-induced target-specific remodeling of BA perisomatic inhibitory synapses originating from parvalbumin and cholecystokinin-positive interneurons. Interestingly, the predicted changes in the balance of perisomatic inhibition matched the silent and active states of the target BA fear neurons. These observations suggest that target-specific changes in perisomatic inhibitory synapses represent a mechanism through which experience can sculpt the activation patterns within a neural circuit. PMID:24183705

  5. Public fear of nuclear technology

    International Nuclear Information System (INIS)

    Excessive fear of nuclear technology (EFONT) is estimated to affect from 35-50 percent of the U.S. public, EFONT is defined as an unpleasant state of fear with components of stress and anxiety, threat to security, and anger. The cognitive aspect of EFONT involves perception of risks, benefits, and values which reinforce and perpetuate the fear. EFONT can be reduced through communications and outreach programs by providing basic information, encouraging participation, and targeting misinformation. Risks need to be put in perspective and benefits made explicit. Safety messages should be combined with other information. Understanding and patience are indispensable in dealing with those who are afraid

  6. Victims' Responses to Stalking: An Examination of Fear Levels and Coping Strategies.

    Science.gov (United States)

    Podaná, Zuzana; Imríšková, Romana

    2016-03-01

    Fear for the stalking victim's own safety or the safety of people close to them is of primary research interest due to the fact that fear is often required as a necessary condition for repetitive intrusive behavior to be defined as stalking. This study examines factors that increase levels of fear in stalking victims and analyzes their coping strategies, making use of data from a victimization survey among citizens of the Czech Republic (N = 2,503). Overall, 147 stalking victims were identified in the sample. Results show that female victims, those stalked by male offenders, and victims pursued over a long period of time, are most fearful. Higher levels of fear are elicited by strangers as opposed to partners or acquaintances. Among stalking practices, only direct aggression is significantly associated with fear, whereas monitoring the victim (comprising typical stalking behavior such as following the victim) increases the perception of the seriousness of stalking, but does not influence the victim's fear. In addition, three behavioral coping strategies have been identified: proactive behavior (47% of victims), avoidance (30%), and passivity (23%). The examination of the association between these coping strategies and victims' fear reveals that female victims, whose behavior is proactive, express higher levels of fear than male victims and than those choosing avoidance or passivity strategies. Overall, the study confirms gender differences in both the level of fear and coping strategies, and lends further support to appeals for eliminating the fear requirement from the stalking definition. PMID:25392391

  7. [GABA-Receptors in Modulation of Fear Memory Extinction].

    Science.gov (United States)

    Dubrovina, N I

    2016-01-01

    GABA is the major inhibitory neurotransmitter in the central nervous system determining the efficacy of neuronal interaction. GABA-receptors play a key role in different aspects of fear memory--acquisition and consolidation, retention, reconsolidation and extinction. Extinction is an important behavioural phenomenon which allows organism to adapt its behavior to a changing environment. Extinction of fear memory is a form of new inhibitory learning which interferes with expression of the initial acquired fear conditioning. Resistance to extinction is symptom of depression and posttraumatic stress disorder. The aim of the present review was to summarize own and literary data about GABAergic modulation of fear extinction and pharmacological correction of extinction impairment at influences on GABA(A)- and GABA(B)- receptors. PMID:27538279

  8. Preventing Return of Fear in an Animal Model of Anxiety: Additive Effects of Massive Extinction and Extinction in Multiple Contexts

    OpenAIRE

    Laborda, Mario A.; Miller, Ralph R.

    2012-01-01

    Fear conditioning and experimental extinction have been presented as models of anxiety disorders and exposure therapy, respectively. Moreover, the return of fear serves as a model of relapse after exposure therapy. Here we present two experiments, with rats as subjects in a lick suppression preparation, in which we assessed the additive effects of two different treatments to attenuate the return of fear. First, we evaluated whether two phenomena known to generate return of fear (i.e., spontan...

  9. The Basolateral Amygdala Determines the Effects of Fear Memory on Sleep in an Animal Model of PTSD

    OpenAIRE

    Wellman, Laurie L.; Fitzpatrick, Mairen E.; Machida, Mayumi; Sanford, Larry D.

    2014-01-01

    Fear conditioning (inescapable shock training (ST)) and fearful context re-exposure (CR) alone can produce significant fear indicated by increased freezing and reductions in subsequent REM sleep. Damage to or inactivation of the basolateral nucleus of the amygdala (BLA) prior to or after ST or prior to CR generally has been found to attenuate freezing in the shock training context. However, no one has examined the impact of BLA inactivation on fear-induced changes in sleep. Here, we used the ...

  10. M-Type Potassium Channels Modulate the Intrinsic Excitability of Infralimbic Neurons and Regulate Fear Expression and Extinction

    OpenAIRE

    Santini, Edwin; James T. Porter

    2010-01-01

    Growing evidence indicates that the activity of infralimbic prefrontal cortex (IL) is critical for inhibiting inappropriate fear responses following extinction learning. Recently, we showed that fear conditioning and extinction alter the intrinsic excitability and bursting of IL pyramidal neurons in brain slices. IL neurons from Sprague Dawley rats expressing high fear had lower intrinsic excitability and bursting than those from rats expressing low fear, suggesting that regulating the intrin...

  11. Fluoxetine Facilitates Fear Extinction Through Amygdala Endocannabinoids.

    Science.gov (United States)

    Gunduz-Cinar, Ozge; Flynn, Shaun; Brockway, Emma; Kaugars, Katherine; Baldi, Rita; Ramikie, Teniel S; Cinar, Resat; Kunos, George; Patel, Sachin; Holmes, Andrew

    2016-05-01

    Pharmacologically elevating brain endocannabinoids (eCBs) share anxiolytic and fear extinction-facilitating properties with classical therapeutics, including the selective serotonin reuptake inhibitor, fluoxetine. There are also known functional interactions between the eCB and serotonin systems and preliminary evidence that antidepressants cause alterations in brain eCBs. However, the potential role of eCBs in mediating the facilitatory effects of fluoxetine on fear extinction has not been established. Here, to test for a possible mechanistic contribution of eCBs to fluoxetine's proextinction effects, we integrated biochemical, electrophysiological, pharmacological, and behavioral techniques, using the extinction-impaired 129S1/Sv1mJ mouse strain. Chronic fluoxetine treatment produced a significant and selective increase in levels of anandamide in the BLA, and an associated decrease in activity of the anandamide-catabolizing enzyme, fatty acid amide hydrolase. Slice electrophysiological recordings showed that fluoxetine-induced increases in anandamide were associated with the amplification of eCB-mediated tonic constraint of inhibitory, but not excitatory, transmission in the BLA. Behaviorally, chronic fluoxetine facilitated extinction retrieval in a manner that was prevented by systemic or BLA-specific blockade of CB1 receptors. In contrast to fluoxetine, citalopram treatment did not increase BLA eCBs or facilitate extinction. Taken together, these findings reveal a novel, obligatory role for amygdala eCBs in the proextinction effects of a major pharmacotherapy for trauma- and stressor-related disorders and anxiety disorders. PMID:26514583

  12. Fluoxetine Facilitates Fear Extinction Through Amygdala Endocannabinoids

    Science.gov (United States)

    Gunduz-Cinar, Ozge; Flynn, Shaun; Brockway, Emma; Kaugars, Katherine; Baldi, Rita; Ramikie, Teniel S; Cinar, Resat; Kunos, George; Patel, Sachin; Holmes, Andrew

    2016-01-01

    Pharmacologically elevating brain endocannabinoids (eCBs) share anxiolytic and fear extinction-facilitating properties with classical therapeutics, including the selective serotonin reuptake inhibitor, fluoxetine. There are also known functional interactions between the eCB and serotonin systems and preliminary evidence that antidepressants cause alterations in brain eCBs. However, the potential role of eCBs in mediating the facilitatory effects of fluoxetine on fear extinction has not been established. Here, to test for a possible mechanistic contribution of eCBs to fluoxetine's proextinction effects, we integrated biochemical, electrophysiological, pharmacological, and behavioral techniques, using the extinction-impaired 129S1/Sv1mJ mouse strain. Chronic fluoxetine treatment produced a significant and selective increase in levels of anandamide in the BLA, and an associated decrease in activity of the anandamide-catabolizing enzyme, fatty acid amide hydrolase. Slice electrophysiological recordings showed that fluoxetine-induced increases in anandamide were associated with the amplification of eCB-mediated tonic constraint of inhibitory, but not excitatory, transmission in the BLA. Behaviorally, chronic fluoxetine facilitated extinction retrieval in a manner that was prevented by systemic or BLA-specific blockade of CB1 receptors. In contrast to fluoxetine, citalopram treatment did not increase BLA eCBs or facilitate extinction. Taken together, these findings reveal a novel, obligatory role for amygdala eCBs in the proextinction effects of a major pharmacotherapy for trauma- and stressor-related disorders and anxiety disorders. PMID:26514583

  13. Alteration of the N-linked Glycosylation Condition of E1 Glycoprotein of Classical Swine Fever Virus Strain Brescia Alters Virulence in Swine

    Science.gov (United States)

    E1, along with Erns and E2 is one of the three envelope glycoproteins of Classical Swine Fever Virus (CSFV). Previously we showed that glycosylation status of virulent CSFV strain Brescia E2 or Erns affects virus virulence. Here, the three putative glycosylation sites of E1 were serially removed by ...

  14. Failure to extinguish fear and genetic variability in the human cannabinoid receptor 1.

    Science.gov (United States)

    Heitland, I; Klumpers, F; Oosting, R S; Evers, D J J; Leon Kenemans, J; Baas, J M P

    2012-01-01

    Failure to extinguish fear can lead to persevering anxiety and has been postulated as an important mechanism in the pathogenesis of human anxiety disorders. In animals, it is well documented that the endogenous cannabinoid system has a pivotal role in the successful extinction of fear, most importantly through the cannabinoid receptor 1. However, no human studies have reported a translation of this preclinical evidence yet. Healthy medication-free human subjects (N=150) underwent a fear conditioning and extinction procedure in a virtual reality environment. Fear potentiation of the eyeblink startle reflex was measured to assess fear-conditioned responding, and subjective fear ratings were collected. Participants were genotyped for two polymorphisms located within the promoter region (rs2180619) and the coding region (rs1049353) of cannabinoid receptor 1. As predicted from the preclinical literature, acquisition and expression of conditioned fear did not differ between genotypes. Crucially, whereas both homozygote (G/G, N=23) and heterozygote (A/G, N=68) G-allele carriers of rs2180619 displayed robust extinction of fear, extinction of fear-potentiated startle was absent in A/A homozygotes (N=51). Additionally, this resistance to extinguish fear left A/A carriers of rs2180619 with significantly higher levels of fear-potentiated startle at the end of the extinction training. No effects of rs1049353 genotype were observed regarding fear acquisition and extinction. These results suggest for the first time involvement of the human endocannabinoid system in fear extinction. Implications are that genetic variability in this system may underlie individual differences in anxiety, rendering cannabinoid receptor 1 a potential target for novel pharmacological treatments of anxiety disorders. PMID:23010766

  15. MODERN IDEOLOGIES OF MANAGING FEAR

    Directory of Open Access Journals (Sweden)

    Oksana Konstantinovna Vasilchenko

    2015-11-01

    Full Text Available The subject of the article is a studying of modern ideologies of managing fear. The purpose of the article is to examine the managing fear practice and explain how it is used in the policy of homeland security. The research methodology is based on the general scientific methods such as analysis and synthesis, induction and deduction and special kind of theoretical me-thods such as studying literature about the problem. The study can be used in courses on social philosophy and political science. The author concludes that social fears are very effective instrument of influence with mass consciousness. The authorities need to legitimize their political decisions through public opinion. But before that they should form it. The author shows how policy of homeland security helps to produce fears in society and how politicians intentionally exaggerate them. In this regard the author considers a concept of homeland security which can eliminate the negative sides of homeland security in future.

  16. Examining the Fears of Gifted Children

    Science.gov (United States)

    Tippey, Jacalyn G.; Burnham, Joy J.

    2009-01-01

    Few studies have considered the fears of gifted children. Using the American Fear Survey Schedule for Children (FSSC-AM; Burnham, 1995), a modified version of the Australian Fear Survey Schedule for Children-II (Gullone & King, 1992, 1993), this study focused on the fears of 287 gifted children ages 7-10. This study is a first step in developing…

  17. Medial Prefrontal Cortex Activation Facilitates Re-Extinction of Fear in Rats

    Science.gov (United States)

    Chang, Chun-hui; Maren, Stephen

    2011-01-01

    It has been suggested that reduced infralimbic (IL) cortical activity contributes to impairments of fear extinction. We therefore explored whether pharmacological activation of the IL would facilitate extinction under conditions it normally fails (i.e., immediate extinction). Rats received auditory fear conditioning 1 h before extinction training.…

  18. Prefrontal Cortex Lesions and Sex Differences in Fear Extinction and Perseveration

    Science.gov (United States)

    Baran, Sarah E.; Armstrong, Charles E.; Niren, Danielle C.; Conrad, Cheryl D.

    2010-01-01

    Electrolytic lesions of the medial prefrontal cortex (PFCX) were examined using fear conditioning to assess the recall of fear extinction and performance in the Y-maze, open field, and object location/recognition in male and female Sprague-Dawley rats. Rats were conditioned to seven tone/footshocks, followed by extinction after 1-h and 24-h…

  19. Elementary charges in classical electrodynamics

    OpenAIRE

    KAPU'{S}CIK, Edward

    1999-01-01

    In the framework of classical electrodynamics elementary particles are treated as capacitors. The electrostatic potentials satisfy equations of the Schrödinger type. An interesting "quantization condition" for elementary charges is derived.

  20. Computerized Dental Injection Fear Treatment

    Science.gov (United States)

    Heaton, L.J.; Leroux, B.G.; Ruff, P.A.; Coldwell, S.E.

    2013-01-01

    One in four adults reports a clinically significant fear of dental injections, leading many to avoid dental care. While systematic desensitization is the most common therapeutic method for treating specific phobias such as fear of dental injections, lack of access to trained therapists, as well as dentists’ lack of training and time in providing such a therapy, means that most fearful individuals are not able to receive the therapy needed to be able to receive necessary dental treatment. Computer Assisted Relaxation Learning (CARL) is a self-paced computerized treatment based on systematic desensitization for dental injection fear. This multicenter, block-randomized, dentist-blind, parallel-group study conducted in 8 sites in the United States compared CARL with an informational pamphlet in reducing fear of dental injections. Participants completing CARL reported significantly greater reduction in self-reported general and injection-specific dental anxiety measures compared with control individuals (p < .001). Twice as many CARL participants (35.3%) as controls (17.6%) opted to receive a dental injection after the intervention, although this was not statistically significant. CARL, therefore, led to significant changes in self-reported fear in study participants, but no significant differences in the proportion of participants having a dental injection (ClinicalTrials.gov, NCT00609648). PMID:23690352

  1. Central HIV-1 Tat exposure elevates anxiety and fear conditioned responses of male mice concurrent with altered mu-opioid receptor-mediated G-protein activation and β-arrestin 2 activity in the forebrain.

    Science.gov (United States)

    Hahn, Yun K; Paris, Jason J; Lichtman, Aron H; Hauser, Kurt F; Sim-Selley, Laura J; Selley, Dana E; Knapp, Pamela E

    2016-08-01

    Co-exposure to opiates and HIV/HIV proteins results in enhanced CNS morphological and behavioral deficits in HIV(+) individuals and in animal models. Opiates with abuse liability, such as heroin and morphine, bind preferentially to and have pharmacological actions through μ-opioid-receptors (MORs). The mechanisms underlying opiate-HIV interactions are not understood. Exposure to the HIV-1 transactivator of transcription (Tat) protein causes neurodegenerative outcomes that parallel many aspects of the human disease. We have also observed that in vivo exposure to Tat results in apparent changes in morphine efficacy, and thus have hypothesized that HIV proteins might alter MOR activation. To test our hypothesis, MOR-mediated G-protein activation was determined in neuroAIDS-relevant forebrain regions of transgenic mice with inducible CNS expression of HIV-1 Tat. G-protein activation was assessed by MOR agonist-stimulated [(35)S]guanosine-5'-O-(3-thio)triphosphate ([(35)S]GTPγS) autoradiography in brain sections, and in concentration-effect curves of MOR agonist-stimulated [(35)S]GTPγS binding in membranes isolated from specific brain regions. Comparative studies were done using the MOR-selective agonist DAMGO ([D-Ala(2), N-MePhe(4), Gly-ol]-enkephalin) and a more clinically relevant agonist, morphine. Tat exposure reduced MOR-mediated G-protein activation in an agonist, time, and regionally dependent manner. Levels of the GPCR regulatory protein β-arrestin-2, which is involved in MOR desensitization, were found to be elevated in only one affected brain region, the amygdala; amygdalar β-arrestin-2 also showed a significantly increased association with MOR by co-immunoprecipitation, suggesting decreased availability of MOR. Interestingly, this correlated with changes in anxiety and fear-conditioned extinction, behaviors that have substantial amygdalar input. We propose that HIV-1 Tat alters the intrinsic capacity of MOR to signal in response to agonist binding

  2. Glucocorticoids reduce phobic fear in humans

    OpenAIRE

    Soravia, Leila M; Heinrichs, Markus; Aerni, Amanda; Maroni, Caroline; Schelling, Gustav; Ehlert, Ulrike; Roozendaal, Benno; de Quervain, Dominique J.-F.

    2006-01-01

    Phobias are characterized by excessive fear, cued by the presence or anticipation of a fearful situation. Whereas it is well established that glucocorticoids are released in fearful situations, it is not known whether these hormones, in turn, modulate perceived fear. As extensive evidence indicates that elevated glucocorticoid levels impair the retrieval of emotionally arousing information, they might also inhibit retrieval of fear memory associated with phobia and, thereby, reduce phobic fea...

  3. Dental Fear among Medical and Dental Undergraduates

    OpenAIRE

    2014-01-01

    Objective. To assess the prevalence and level of dental fear among health related undergraduates and to identify factors causing such fear using Kleinknecht's Dental Fear Survey (DFS) questionnaire. Methods. Kleinknecht's DFS questionnaire was used to assess dental fear and anxiety among the entire enrollment of the medical and dental undergraduates' of the University of Malaya. Results. Overall response rate was 82.2%. Dental students reported higher prevalence of dental fear (96.0% versus 9...

  4. Finding theory- and evidence-based alternatives to fear appeals: Intervention Mapping

    OpenAIRE

    Kok, Gerjo; Bartholomew, L Kay; Parcel, Guy S.; Gottlieb, Nell H; Fernández, María E.

    2013-01-01

    Fear arousal—vividly showing people the negative health consequences of life-endangering behaviors—is popular as a method to raise awareness of risk behaviors and to change them into health-promoting behaviors. However, most data suggest that, under conditions of low efficacy, the resulting reaction will be defensive. Instead of applying fear appeals, health promoters should identify effective alternatives to fear arousal by carefully developing theory- and evidence-based programs. The Interv...

  5. Automated scoring of fear related behavior using EthoVision software

    OpenAIRE

    Pham, Jon; Cabrera, Sara M.; Sanchis-Segura, Carles; Wood, Marcelo A.

    2008-01-01

    Fear conditioning is a frequently used paradigm for assessing learning and memory in rodents. Traditionally researchers have relied upon scoring of fear related behavior by human observation, which can be difficult and subjective and thus vary among investigators. The goal of this study was to evaluate the ability of EthoVision tracking software (Noldus Information Technology, Inc.) to reliably and accurately score fear related behavior in mice. Specifically, we were interested in its ability...

  6. The role of fear in mental health service users’ experiences: a qualitative exploration

    OpenAIRE

    Sweeney, Angela; Gillard, Steve; Wykes, Til; Rose, Diana

    2015-01-01

    Purpose Although studies suggest that fear plays an important role in shaping mental health service users’ experiences, evidence is patchy and the contexts, conditions and consequences of fear have rarely been researched. This paper explores the role of fear in adult mental health service users’ lives and describes its implications for mental health services. Methods Four community health service user focus groups (N32) were held. Each group was reconvened after 7–14 days. An initial thematic...

  7. The Formation and Extinction of Fear Memory in Tree Shrews

    Directory of Open Access Journals (Sweden)

    Shujiang eShang

    2015-07-01

    Full Text Available Fear is an emotion that is well studied due to its importance for animal survival. Experimental animals, such as rats and mice, have been widely used to model fear. However, higher animals such as nonhuman primates have rarely been used to study fear due to ethical issues and high costs. Tree shrews are small mammals that are closely related to primates; they have been used to model human-related psychosocial conditions such as stress and alcohol tolerance. Here, we describe an experimental paradigm to study the formation and extinction of fear memory in tree shrews. We designed an experimental apparatus of a light/dark box with a voltage foot shock. We found that tree shrews preferred staying in the dark box in the daytime without stimulation and showed avoidance to voltage shocks applied to the footplate in a voltage-dependent manner. Foot shocks applied to the dark box for 5 days (10 minutes per day effectively reversed the light–dark preference of the tree shrews, and this memory lasted for more than 50 days without any sign of memory decay (extinction in the absence of further stimulation. However, this fear memory was reversed with 4 days of reverse training by applying the same stimulus to the light box. When reducing the stimulus intensity during the training period, a memory extinction and subsequently reinstatement effects were observed. Thus, our results describe an efficient method of monitoring fear memory formation and extinction in tree shrews.

  8. Coupled contagion dynamics of fear and disease: mathematical and computational explorations.

    Directory of Open Access Journals (Sweden)

    Joshua M Epstein

    Full Text Available BACKGROUND: In classical mathematical epidemiology, individuals do not adapt their contact behavior during epidemics. They do not endogenously engage, for example, in social distancing based on fear. Yet, adaptive behavior is well-documented in true epidemics. We explore the effect of including such behavior in models of epidemic dynamics. METHODOLOGY/PRINCIPAL FINDINGS: Using both nonlinear dynamical systems and agent-based computation, we model two interacting contagion processes: one of disease and one of fear of the disease. Individuals can "contract" fear through contact with individuals who are infected with the disease (the sick, infected with fear only (the scared, and infected with both fear and disease (the sick and scared. Scared individuals--whether sick or not--may remove themselves from circulation with some probability, which affects the contact dynamic, and thus the disease epidemic proper. If we allow individuals to recover from fear and return to circulation, the coupled dynamics become quite rich, and can include multiple waves of infection. We also study flight as a behavioral response. CONCLUSIONS/SIGNIFICANCE: In a spatially extended setting, even relatively small levels of fear-inspired flight can have a dramatic impact on spatio-temporal epidemic dynamics. Self-isolation and spatial flight are only two of many possible actions that fear-infected individuals may take. Our main point is that behavioral adaptation of some sort must be considered.

  9. Extinction Circuits for Fear and Addiction Overlap in Prefrontal Cortex

    Science.gov (United States)

    Peters, Jamie; Kalivas, Peter W.; Quirk, Gregory J.

    2009-01-01

    Extinction is a form of inhibitory learning that suppresses a previously conditioned response. Both fear and drug seeking are conditioned responses that can lead to maladaptive behavior when expressed inappropriately, manifesting as anxiety disorders and addiction, respectively. Recent evidence indicates that the medial prefrontal cortex (mPFC) is…

  10. Prediction of individual differences in fear response by novelty seeking, and disruption of contextual fear memory reconsolidation by ketamine.

    Science.gov (United States)

    Duclot, Florian; Perez-Taboada, Iara; Wright, Katherine N; Kabbaj, Mohamed

    2016-10-01

    Only a portion of the population exposed to trauma will develop persistent emotional alterations characteristic of posttraumatic stress disorder (PTSD), which illustrates the necessity for identifying vulnerability factors and novel pharmacotherapeutic alternatives. Interestingly, clinical evidence suggests that novelty seeking is a good predictor for vulnerability to the development of excessive and persistent fear. Here, we first tested this hypothesis by analyzing contextual and cued fear responses of rats selected for their high (high responders, HR) or low (low responders, LR) exploration of a novel environment, indicator of novelty seeking. While HR and LR rats exhibited similar sensitivity to the shock and cued fear memory retention, fewer extinction sessions were required in HR than LR animals to reach extinction, indicating faster contextual and cued memory extinction. In a second part, we found an effective disruption of contextual fear reconsolidation by the N-methyl-d-aspartate receptor antagonist ketamine, associated with a down-regulation of early growth response 1 (Egr1) in the hippocampal CA1 area, and up-regulation of brain-derived neurotrophic factor (Bdnf) mRNA levels in the prelimbic and infralimbic cortices. Altogether, these data demonstrate a link between novelty seeking and conditioned fear extinction, and highlight a promising novel role of ketamine in affecting established fear memory. PMID:27343386

  11. How Administration of the Beta-Blocker Propranolol Before Extinction can Prevent the Return of Fear.

    Science.gov (United States)

    Kroes, Marijn C W; Tona, Klodiana-Daphne; den Ouden, Hanneke E M; Vogel, Susanne; van Wingen, Guido A; Fernández, Guillén

    2016-05-01

    Combining beta-blockers with exposure therapy has been advocated to reduce fear, yet experimental studies combining beta-blockers with memory reactivation have had contradictory results. We explored how beta-blockade might affect the course of safety learning and the subsequent return of fear in a double-blind placebo-controlled functional magnetic resonance imaging study in humans (N=46). A single dose of propranolol before extinction learning caused a loss of conditioned fear responses, and prevented the subsequent return of fear and decreased explicit memory for the fearful events in the absence of drug. Fear-related neural responses were persistently attenuated in the dorsal medial prefrontal cortex (dmPFC), increased in the hippocampus 24 h later, and correlated with individual behavioral indices of fear. Prediction error-related responses in the ventral striatum persisted during beta-blockade. We suggest that this pattern of results is most consistent with a model where beta-blockade can prevent the return of fear by (i) reducing retrieval of fear memory, via the dmPFC and (ii) increasing contextual safety learning, via the hippocampus. Our findings suggest that retrieval of fear memory and contextual safety learning form potential mnemonic target mechanisms to optimize exposure-based therapy with beta-blockers. PMID:26462618

  12. Early adversity disrupts the adult use of aversive prediction errors to reduce fear in uncertainty

    Directory of Open Access Journals (Sweden)

    Kristina M Wright

    2015-08-01

    Full Text Available Early life adversity increases anxiety in adult rodents and primates, and increases the risk for developing post-traumatic disorder (PTSD in humans. We hypothesized that early adversity impairs the use of learning signals – negative, aversive prediction errors – to reduce fear in uncertainty. To test this hypothesis, we gave adolescent rats a battery of adverse experiences then assessed adult performance in probabilistic Pavlovian fear conditioning and fear extinction. Rats were confronted with three cues associated with different probabilities of foot shock: one cue never predicted shock, another cue predicted shock with uncertainty, and a final cue always predicted shock. Control rats initially acquired fear to all cues, but rapidly reduced fear to the non-predictive and uncertain cues. Early adversity rats were slower to reduce fear to the non-predictive cue and never fully reduced fear to the uncertain cue. In extinction, all cues were presented in the absence of shock. Fear to the uncertain cue in discrimination, but not early adversity itself, predicted the reduction of fear in extinction. These results demonstrate early adversity impairs the use of negative, aversive prediction errors to reduce fear, especially in situations of uncertainty.

  13. Stimulus fear-relevance and the vicarious learning pathway to childhood fears

    OpenAIRE

    Askew, C.; Dunne, G.; Ozdil, A; Reynolds, G; Field, A.P.

    2013-01-01

    Enhanced fear learning for fear-relevant stimuli has been demonstrated in procedures with adults in the laboratory. Three experiments investigated the effect of stimulus fear-relevance on vicarious fear learning in children (aged 6-11 years). Pictures of stimuli with different levels of fear-relevance (flowers, caterpillars, snakes, worms, and Australian marsupials) were presented alone or together with scared faces. In line with previous studies, children's fear beliefs and avoidance prefere...

  14. The extinction of conditioned fear: structural and molecular basis and therapeutic use A extinção do medo condicionado: bases estruturais e moleculares e utilização terapêutica

    Directory of Open Access Journals (Sweden)

    Martín Cammarota

    2007-03-01

    Full Text Available OBJECTIVE: Through association, a large variety of stimuli acquire the property of signaling pleasant or aversive events. Pictures of a wedding or of a plane disaster may serve as cues to recall these events and/or others of a similar nature or emotional tone. Presentation of the cues unassociated with the events, particularly if repeated, reduces the tendency to retrieve the original learning based on that association. This attenuation of the expression of a learned response was discovered by Pavlov 100 years ago, who called it extinction. In this article we review some of the most recent findings about the behavioral and biochemical properties of extinction. RESULTS AND DISCUSSION: It has been shown that extinction is a new learning based on a new link formed by the cues and the absence of the original event(s which originated the first association. Extinction does not consist of the erasure of the original memory, but of an inhibition of its retrieval: the original response reappears readily if the former association is reiterated, or if enough time is allowed to pass (spontaneous recovery. Extinction requires neural activity, signaling pathways, gene expression and protein synthesis in the ventromedial prefrontal cortex and/or basolateral amygdala, hippocampus, entorhinal cortex and eventually other areas. The site or sites of extinction vary with the task. CONCLUSIONS: Extinction was advocated by Freud in the 1920's for the treatment of phobias, and is used in cognitive therapy to treat diseases that rely on conditioned fear (phobias, panic, and particularly posttraumatic stress disorder. The treatment of learned fear disorders with medications is still unsatisfactory although some have been shown useful when used as adjuncts to behavioral therapy.OBJETIVO: Muitos estímulos podem adquirir características prazerosas ou aversivas por meio da formação de associações. Fotografias de um casamento ou de um acidente aeronáutico podem servir

  15. Memory-emotional interactions as revealed by fear generalization in animal-fearful individuals.

    Science.gov (United States)

    Kopp, Bruno; Schlimm, Mike; Hermann, Christiane

    2005-06-01

    Discriminative fear learning and fear generalization were examined in animal-fearful individuals and in control participants. Electrical shocks were administered contingent upon discriminative pictures of spiders or snakes, respectively, in a generalization-after-discrimination paradigm. Neither discriminative fear learning nor extinction was affected by the individual fear status of the animal categories. Novel feared stimuli, which resembled discriminative stimuli, were treated as more shock predictive than novel non-feared stimuli during generalization testing. Neither preparedness theory nor selective sensitization theory was capable to account for these observations. The findings are commensurable with the hypothesis that phobic fear interferes with the retrieval of memory traces. PMID:15814082

  16. Fear of acquired immunodeficiency syndrome and fear of other illness in suicide

    DEFF Research Database (Denmark)

    Aro, A R; Jallinoja, P T; Henriksson, M M; Lönnqvist, J K

    1994-01-01

    other suicides. Suicidal fear of AIDS calls for evaluation of sexual and other risk behaviour, but fear of AIDS was largely generated by the extensive media coverage. Fear of other somatic illness was more diverse in origin and related to illness experiences. Suicidal fear of illness calls for......Suicide victims with fear of acquired immunodeficiency syndrome (AIDS) or other somatic illness were compared for psychosocial and health-related characteristics, triggers and content of fear. Fear of AIDS cases (n = 28), 2% of the 1-year Finnish suicide population (n = 1397), were younger and...... recognition of depression and differentiation of the origin and content of fear....

  17. Fear extinction as a model for translational neuroscience: ten years of progress.

    Science.gov (United States)

    Milad, Mohammed R; Quirk, Gregory J

    2012-01-01

    The psychology of extinction has been studied for decades. Approximately 10 years ago, however, there began a concerted effort to understand the neural circuits of extinction of fear conditioning, in both animals and humans. Progress during this period has been facilitated by a high degree of coordination between rodent and human researchers examining fear extinction. Here we review the major advances and highlight new approaches to understanding and exploiting fear extinction. Research in fear extinction could serve as a model for translational research in other areas of behavioral neuroscience. PMID:22129456

  18. Part 2: Fear of contagion, fear of intimacy.

    Science.gov (United States)

    Botnick, M R

    2000-01-01

    In this second part of the trilogy, I review the concepts of panic, the Theory of Cognitive Dissonance, and how internally inconsistent opinions and attitudes can be made consistent (or consonant). The theory explains, in some measure, how AIDS has been socialized into our thinking about identity, and goes beyond a medical condition. The pervasive identification of gay men with HIV and AIDS has resulted for many in an over-identification with fears of contagion and on a societal level in a fear of all gays as pools of contagion. The conversion of dissonance to consonance has taken many forms; within the gay community it has resulted in the rejection of the "100% safe-100% of the time" safe-sex message, and the adoption (for many) of a new form of deviant label-someone who is not in conformity with the social norm of gay community sexual behavior. However, we shall see that this so-called norm is a sham-that many gay men do not, as a rule, practice safe(r) sex on a consistent basis. This information indicates that the educational efforts of the last decade have at best lost their potency, and at worst were less than efficacious to begin with. The dissonant messages have also informed both the construction of the gay community and its interpretation of what it means to be gay. The result has been a tri-lateral perception of HIV and AIDS as either a medical, political or a social phenomenon. This fragmented understanding has exacerbated the already polarized ASOs and GSOs in that each has determined its ideology based on a particular interpretation of HIV and AIDS. This polarization has been operationalized by the GSOs and ASOs primarily in the manner by which they define their target markets, and more importantly, in the manner by which they exclude certain gays from participation. At the extreme, some gay men feel entirely left out of the community, and are consequently unable to convert their dissonance regarding being gay into consonance, if only by developing

  19. Fear experience reading: women reading

    Directory of Open Access Journals (Sweden)

    Sofia VALDIVIESO GÁMEZ

    2009-11-01

    Full Text Available Starting from the assumptions the patriarchal paradigm has used in the construction of male and female identity, the changes experienced by women in the last century and the statements about fear undergone by more than twenty-five women from different ages and nationalities through their own life cycle, the author gives us an account on what women fear and how they live and overcome it. These ideas are based on the hypothesis that if patriarchy as a social organization is a cultural constant, the fears experienced by women in the process of constructing themselves as such are also constant. She concludes that the only course to follow is necessarily a way where feminine consciousness must be integrated, both in men and women, as a previous step in the construction of a reality based on equals, though, at the same time, different. This would allow us to discover the masculine and feminine dimension in all of us.

  20. Towards new approaches to disorders of fear and anxiety.

    Science.gov (United States)

    Dias, Brian G; Banerjee, Sunayana B; Goodman, Jared V; Ressler, Kerry J

    2013-06-01

    Fear and anxiety are debilitating conditions that affect a significant number of individuals in their lifetimes. Understanding underlying mechanisms of these disorders affords us the possibility of therapeutic intervention. Such clarity in terms of mechanism and intervention can only come from an amalgamation of research from human to animal studies that attempt to mimic the human condition, both of which are discussed in this review. We begin by presenting an outline of our current understanding of the neurobiological basis of fear and anxiety. This outline spans various levels of organization that include the circuitry, molecular pathways, genetic and epigenetic components of fear and anxiety. Using these organizational levels as a scaffold, we then discuss strategies that are currently used to ameliorate these disorders, and forecast future interventions that hold therapeutic promise. Among these newer promising treatments, we include, optogenetic, pharmacological, and extinction-based approaches, as well as lifestyle modifications, with combinatorial treatment regimens of these holding the most promise. PMID:23402950

  1. Laterodorsal tegmentum interneuron subtypes oppositely regulate olfactory cue-induced innate fear.

    Science.gov (United States)

    Yang, Hongbin; Yang, Junhua; Xi, Wang; Hao, Sijia; Luo, Benyan; He, Xiaobin; Zhu, Liya; Lou, Huifang; Yu, Yan-Qin; Xu, Fuqiang; Duan, Shumin; Wang, Hao

    2016-02-01

    Innate fear has a critical role in survival of animals. Unlike conditioned fear, the neuronal circuitry underlying innate fear is largely unknown. We found that the laterodorsal tegmentum (LDT) and lateral habenula (LHb) are specifically activated by the mouse predator odorant trimethylthiazoline (TMT). Using optogenetics to selectively stimulate GABAergic neurons in the LDT immediately produced fear-like responses (freezing, accelerated heart rate and increased serum corticosterone), whereas prolonged stimulation caused anxiety-like behaviors. Notably, although selective stimulation of parvalbumin (PV)-positive interneurons similarly induced fear-like responses, stimulation of somatostatin-positive interneurons or inhibition of PV neurons in the LDT suppressed TMT-induced fear-like responses without affecting conditioned fear. Finally, activation of LHb glutamatergic inputs to LDT interneurons was sufficient to generate fear-like responses. Thus, the LHb-LDT pathway is important for regulating olfactory cue-induced innate fear. Our results provide a potential target for therapeutic intervention for anxiety disorder. PMID:26727549

  2. EphrinA4 mimetic peptide targeted to EphA binding site impairs the formation of long-term fear memory in lateral amygdala

    OpenAIRE

    Dines, M; Lamprecht, R.

    2014-01-01

    Fear conditioning leads to long-term fear memory formation and is a model for studying fear-related psychopathologies conditions such as phobias and posttraumatic stress disorder. Long-term fear memory formation is believed to involve alterations of synaptic efficacy mediated by changes in synaptic transmission and morphology in lateral amygdala (LA). EphrinA4 and its cognate Eph receptors are intimately involved in regulating neuronal morphogenesis, synaptic transmission and plasticity. To a...

  3. Fear experience reading: women reading

    OpenAIRE

    Sofia VALDIVIESO GÁMEZ

    2009-01-01

    Starting from the assumptions the patriarchal paradigm has used in the construction of male and female identity, the changes experienced by women in the last century and the statements about fear undergone by more than twenty-five women from different ages and nationalities through their own life cycle, the author gives us an account on what women fear and how they live and overcome it. These ideas are based on the hypothesis that if patriarchy as a social organization is a cultural constant,...

  4. Fear Not: Neurobiological Mechanisms of Fear and Anxiety

    NARCIS (Netherlands)

    Klumpers, F.

    2012-01-01

    Fear is a common, core emotion. Moreover, anxiety disorders are among the most common form of psychiatric disease. In this thesis neuroimaging, genetic, pharmacological, brain stimulation and behavioral techniques were used in healthy subjects and specific patient populations to shed more light on t

  5. Elites and Panic: More to Fear than Fear Itself

    Science.gov (United States)

    Clarke, Lee; Chess, Caron

    2008-01-01

    Attributions of panic are almost exclusively directed at members of the general public. Here, we inquire into the relationships between elites and panic. We review current research and theorizing about panic, including problems of identifying when it has occurred. We propose three relationships: elites fearing panic, elites causing panic and…

  6. Fear of blushing : fearful preoccupation irrespective of facial coloration

    NARCIS (Netherlands)

    Mulkens, S; de Jong, Peter; Dobbelaar, A; Bogels, SM

    1999-01-01

    Women, with high (n = 29) and low (n = 28) fear of blushing, were exposed to a mild social stressor (watching a television test card in the presence of two male confederates) and to an intense social stressor (watching their own prerecorded 'sing' video, in the presence of two male confederates). Fa

  7. Delayed Recall of Fear Extinction in Rats with Lesions of Ventral Medial Prefrontal Cortex

    Science.gov (United States)

    Lebron, Kelimer; Milad, Mohammed R.; Quirk, Gregory J.

    2004-01-01

    Extinction of auditory fear conditioning is thought to form a new memory. We previously found that rats with vmPFC lesions could extinguish fear to the tone within a session, but showed no recall of extinction 24 h later. One interpretation is that the vmPFC is the sole storage site of extinction memory. However, it is also possible that lesioned…

  8. Mechanics classical and quantum

    CERN Document Server

    Taylor, T T

    2015-01-01

    Mechanics: Classical and Quantum explains the principles of quantum mechanics via the medium of analytical mechanics. The book describes Schrodinger's formulation, the Hamilton-Jacobi equation, and the Lagrangian formulation. The author discusses the Harmonic Oscillator, the generalized coordinates, velocities, as well as the application of the Lagrangian formulation to systems that are partially or entirely electromagnetic in character under certain conditions. The book examines waves on a string under tension, the isothermal cavity radiation, and the Rayleigh-Jeans result pertaining to the e

  9. Blindness Biggest Fear for Many Americans

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_160254.html Blindness Biggest Fear for Many Americans Losing vision would ... 4, 2016 THURSDAY, Aug. 4, 2016 (HealthDay News) -- Blindness is what many Americans fear most, a new ...

  10. Fear as an object of aesthetic reflection in parodies of the gothic novel

    Directory of Open Access Journals (Sweden)

    Moysik Natalya Grigorievna

    2015-06-01

    Full Text Available The article explores superstitious fear artistically represented in the Gothic novels by Ann Radcliffe (The Romance of the Forest, 1791; The Mysteries of Udolfo, 1794; The Italian, 1797 and in late 18th -19th century parodies of the Gothic novel (Northanger Abbey, 1818, by J. Austen; Nightmare Abbey, 1818, by T.L. Peacock; Heroine, 1813, by E.S. Barrett, and some others. It is found out that the representations of superstitious fear bear satirical character already in the novels by Radcliffe which are known to be the classic of the Gothic genre, the satire becoming yet more explicit in the parodies of the Gothic novel. Several types of the “Gothic” fear descriptions are distinguished. It is argued that the scenes of superstitious fear in the abovementioned novels and parodies are aimed against irrational Gothic mode of perception and meant to praise the rational way of thinking, characteristic of the Enlightment.

  11. When the mind forms fear: embodied fear knowledge potentiates bodily reactions

    NARCIS (Netherlands)

    S. Oosterwijk; M. Topper; M. Rotteveel; A.H. Fischer

    2010-01-01

    In the present study, the authors tested whether conceptual fear knowledge can (a) evoke bodily reactions and (b) enhance subsequent bodily reactions to fearful stimuli. Participants unscrambled neutral or fear sentences and subsequently viewed fearful and neutral pictures in combination with startl

  12. Stimulation of serotonin 2A receptors facilitates consolidation and extinction of fear memory in C57BL/6J mice

    OpenAIRE

    Zhang, Gongliang; Asgeirsdottir, Herborg N.; Cohen, Sarah J.; Munchow, Alcira H.; Barrera, Mercy P.; Stackman, Robert W.

    2012-01-01

    Excessive fear is a hallmark of several emotional and mental disorders such as phobias and panic disorders. Considerable attention is focused on defining the neurobiological mechanisms of the extinction of conditioned fear memory in an effort to identify mechanisms that may hold clinical significance for remediating aberrant fear memory. Serotonin modulates the acquisition and retention of conditioned emotional memory, and the serotonin 2A receptor (5HT2AR) may be one of the postsynaptic targ...

  13. Fears of American Children Following Terrorism

    Science.gov (United States)

    Burnham, Joy J.; Hooper, Lisa M.

    2008-01-01

    Two months after 9/11, the fears of children and adolescents in Grades 2-12 were examined utilizing the American Fear Survey Schedule for Children and Adolescents (FSSC-AM). Fear intensity scores and age and gender differences are reported. Terrorist-related content on the FSSC-AM (e.g., terrorist attacks, our country being invading by enemies)…

  14. Gun Attitudes and Fear of Crime.

    Science.gov (United States)

    Heath, Linda; Weeks, Kyle; Murphy, Marie Mackay

    1997-01-01

    Using three studies, examined the relationship between attitudes toward guns and fear of crime. Findings indicate a connection between fear of crime and attitudes toward guns: people higher in fear of crime favored gun control. Results also established a relationship between stereotypical beliefs about gun victims and support for gun control. (RJM)

  15. Anxiety, Fears, and Phobias (For Parents)

    Science.gov (United States)

    ... fears that stem from childhood experiences. An adult's fear of public speaking may be the result of embarrassment in front of peers many years before. It's important for parents to recognize and identify the signs and symptoms of kids' anxieties so that fears don't get in the way of everyday ...

  16. Impact of Predatory Threat on Fear Extinction in Lewis Rats

    Science.gov (United States)

    Goswami, Sonal; Cascardi, Michele; Rodriguez-Sierra, Olga E.; Duvarci, Sevil; Pare, Denis

    2010-01-01

    Humans with post-traumatic stress disorder (PTSD) are deficient at extinguishing conditioned fear responses. A study of identical twins concluded that this extinction deficit does not predate trauma but develops as a result of trauma. The present study tested whether the Lewis rat model of PTSD reproduces these features of the human syndrome.…

  17. Effects of Lidocaine with Epinephrine on Fear Related Arousal Among Dental Phobics

    OpenAIRE

    Fiset, Louis; Ramsay, Douglas; Milgrom, Peter; Weinstein, Philip

    1986-01-01

    The effects of 2% lidocaine containing 72 μg epinephrine on fear related arousal were tested using a cross-over design on dental patients fearful of injections and other dental procedures. Heart rate and body movement in the dental operatory were monitored, and subjects' self-reported upset in the Epinephrine condition than in the No-Epinephrine condition (F = 4.8, p = .04), but the clinical significance was negligible. No interaction between initial fear levels and the drug condition could b...

  18. Mechanisms of estradiol in fear circuitry: implications for sex differences in psychopathology.

    Science.gov (United States)

    Cover, K K; Maeng, L Y; Lebrón-Milad, K; Milad, M R

    2014-01-01

    Over the past two decades, substantial knowledge has been attained about the mechanisms underlying the acquisition and subsequent extinction of conditioned fear. Knowledge gained on the biological basis of Pavlovian conditioning has led to the general acceptance that fear extinction may be a useful model in understanding the underlying mechanisms in the pathophysiology of anxiety disorders and may also be a good model for current therapies treating these disorders. Lacking in the current knowledge is how men and women may or may not differ in the biology of fear and its extinction. It is also unclear how the neural correlates of fear extinction may mediate sex differences in the etiology, maintenance, and prevalence of psychiatric disorders. In this review, we begin by highlighting the epidemiological differences in incidence rate. We then discuss how estradiol (E2), a primary gonadal hormone, may modulate the mechanisms of fear extinction and mediate some of the sex differences observed in psychiatric disorders. PMID:25093600

  19. Recognizing Student Fear: The Elephant in the Classroom

    Science.gov (United States)

    Bledsoe, T. Scott; Baskin, Janice J.

    2014-01-01

    Understanding fear, its causes, and its impact on students can be important for educators who seek ways to help students manage their fears. This paper explores common types of student fears such as performance-based anxiety, fear of failure, fear of being laughed at, and cultural components of fear that impact learning. The cognitive, emotional,…

  20. Numerical stability of finite difference algorithms for electrochemical kinetic simulations: Matrix stability analysis of the classic explicit, fully implicit and Crank-Nicolson methods and typical problems involving mixed boundary conditions

    DEFF Research Database (Denmark)

    Bieniasz, Leslaw K.; Østerby, Ole; Britz, Dieter

    1995-01-01

    The stepwise numerical stability of the classic explicit, fully implicit and Crank-Nicolson finite difference discretizations of example diffusional initial boundary value problems from electrochemical kinetics has been investigated using the matrix method of stability analysis. Special attention...... has been paid to the effect of the discretization of the mixed, linear boundary condition with time-dependent coefficients on stability, assuming the two-point forward-difference approximations for the gradient at the left boundary (electrode). Under accepted assumptions one obtains the usual...