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Sample records for learning leave extinction

  1. Context, Learning, and Extinction

    ERIC Educational Resources Information Center

    Gershman, Samuel J.; Blei, David M.; Niv, Yael

    2010-01-01

    A. Redish et al. (2007) proposed a reinforcement learning model of context-dependent learning and extinction in conditioning experiments, using the idea of "state classification" to categorize new observations into states. In the current article, the authors propose an interpretation of this idea in terms of normative statistical inference. They…

  2. Context, Learning, and Extinction

    ERIC Educational Resources Information Center

    Gershman, Samuel J.; Blei, David M.; Niv, Yael

    2010-01-01

    A. Redish et al. (2007) proposed a reinforcement learning model of context-dependent learning and extinction in conditioning experiments, using the idea of "state classification" to categorize new observations into states. In the current article, the authors propose an interpretation of this idea in terms of normative statistical inference. They…

  3. The learning of fear extinction.

    PubMed

    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.

  4. Neural Mechanisms of Extinction Learning and Retrieval

    PubMed Central

    Quirk, Gregory J.; Mueller, Devin

    2009-01-01

    Emotional learning is necessary for individuals to survive and prosper. Once acquired, however, emotional associations are not always expressed. Indeed, the regulation of emotional expression under varying environmental conditions is essential for mental health. The simplest form of emotional regulation is extinction, in which conditioned responding to a stimulus decreases when the reinforcer is omitted. Two decades of research on the neural mechanisms of fear conditioning have laid the groundwork for understanding extinction. In this review, we summarize recent work on the neural mechanisms of extinction learning. Like other forms of learning, extinction occurs in three phases: acquisition, consolidation, and retrieval, each of which depends on specific structures (amygdala, prefrontal cortex, hippocampus), and molecular mechanisms (receptors and signaling pathways). Pharmacological methods to facilitate consolidation and retrieval of extinction, for both aversive and appetitive conditioning, are setting the stage for novel treatments for anxiety disorders and addictions. PMID:17882236

  5. Modulation of the extinction of fear learning.

    PubMed

    Myskiw, Jociane C; Izquierdo, Ivan; Furini, Cristiane R G

    2014-06-01

    We review recent work on extinction learning with emphasis on its modulation. Extinction is the learned inhibition of responding to previously acquired tasks. Like other forms of learning, it can be modulated by a variety of neurotransmitter systems and behavioral procedures. This bears on its use in the treatment of fear memories, particularly in posttraumatic stress disorder (PTSD), for which it is the treatment of choice, often under the name of exposure therapy. There have not been many laboratories interested in the modulation of extinction, but the available data, although not very abundant, are quite conclusive. Most studies on the nature of extinction and on its modulation have been carried out on fear motivated behaviors, possibly because of their applicability to the therapy of PTSD. A role for d-serine and the glycine site of NMDA receptors has been ascertained in two forms of extinction in the ventromedial prefrontal cortex, basolateral amygdala and dorsal hippocampus. The serine analog, d-cycloserine, has received clinical trials as an enhancer of extinction. The brain histaminergic system acting via H2 receptors, and the endocannabinoid system using CB1 receptors in the ventromedial prefrontal cortex, hippocampus and basolateral amygdala enhance extinction. Dopaminergic D1 and ß-noradrenergic receptors also modulate extinction by actions on these three structures. Isolated findings suggest roles for on serotonin-1A, dopaminergic-D2 and a- and ß-noradrenergic receptors in extinction modulation. Importantly, behavioral tagging and capture mechanisms in the hippocampus have been shown to play a major modulatory role in extinction. In addition, extinction of at least one aversive task (inhibitory avoidance) can be made state dependent on peripheral epinephrine.

  6. Stress before extinction learning enhances and generalizes extinction memory in a predictive learning task.

    PubMed

    Meir Drexler, Shira; Hamacher-Dang, Tanja C; Wolf, Oliver T

    2017-04-08

    In extinction learning, the individual learns that a previously acquired association (e.g. between a threat and its predictor) is no longer valid. This learning is the principle underlying many cognitive-behavioral psychotherapeutic treatments, e.g. 'exposure therapy'. However, extinction is often highly-context dependent, leading to renewal (relapse of extinguished conditioned response following context change). We have previously shown that post-extinction stress leads to a more context-dependent extinction memory in a predictive learning task. Yet as stress prior to learning can impair the integration of contextual cues, here we aim to create a more generalized extinction memory by inducing stress prior to extinction. Forty-nine men and women learned the associations between stimuli and outcomes in a predictive learning task (day 1), extinguished them shortly after an exposure to a stress/control condition (day 2), and were tested for renewal (day 3). No group differences were seen in acquisition and extinction learning, and a renewal effect was present in both groups. However, the groups differed in the strength and context-dependency of the extinction memory. Compared to the control group, the stress group showed an overall reduced recovery of responding to the extinguished stimuli, in particular in the acquisition context. These results, together with our previous findings, demonstrate that the effects of stress exposure on extinction memory depend on its timing. While post-extinction stress makes the memory more context-bound, pre-extinction stress strengthens its consolidation for the acquisition context as well, making it potentially more resistant to relapse. These results have implications for the use of glucocorticoids as extinction-enhancers in exposure therapy.

  7. Cholinergic regulation of fear learning and extinction.

    PubMed

    Wilson, Marlene A; Fadel, Jim R

    2017-03-01

    Cholinergic activation regulates cognitive function, particularly long-term memory consolidation. This Review presents an overview of the anatomical, neurochemical, and pharmacological evidence supporting the cholinergic regulation of Pavlovian contextual and cue-conditioned fear learning and extinction. Basal forebrain cholinergic neurons provide inputs to neocortical regions and subcortical limbic structures such as the hippocampus and amygdala. Pharmacological manipulations of muscarinic and nicotinic receptors support the role of cholinergic processes in the amygdala, hippocampus, and prefrontal cortex in modulating the learning and extinction of contexts or cues associated with threat. Additional evidence from lesion studies and analysis of in vivo acetylcholine release with microdialysis similarly support a critical role of cholinergic neurotransmission in corticoamygdalar or corticohippocampal circuits during acquisition of fear extinction. Although a few studies have suggested a complex role of cholinergic neurotransmission in the cellular plasticity essential for extinction learning, more work is required to elucidate the exact cholinergic mechanisms and physiological role of muscarinic and nicotinic receptors in these fear circuits. Such studies are important for elucidating the role of cholinergic neurotransmission in disorders such as posttraumatic stress disorder that involve deficits in extinction learning as well as for developing novel therapeutic approaches for such disorders. © 2016 Wiley Periodicals, Inc.

  8. Estimating extinction using unsupervised machine learning

    NASA Astrophysics Data System (ADS)

    Meingast, Stefan; Lombardi, Marco; Alves, João

    2017-05-01

    Dust extinction is the most robust tracer of the gas distribution in the interstellar medium, but measuring extinction is limited by the systematic uncertainties involved in estimating the intrinsic colors to background stars. In this paper we present a new technique, Pnicer, that estimates intrinsic colors and extinction for individual stars using unsupervised machine learning algorithms. This new method aims to be free from any priors with respect to the column density and intrinsic color distribution. It is applicable to any combination of parameters and works in arbitrary numbers of dimensions. Furthermore, it is not restricted to color space. Extinction toward single sources is determined by fitting Gaussian mixture models along the extinction vector to (extinction-free) control field observations. In this way it becomes possible to describe the extinction for observed sources with probability densities, rather than a single value. Pnicer effectively eliminates known biases found in similar methods and outperforms them in cases of deep observational data where the number of background galaxies is significant, or when a large number of parameters is used to break degeneracies in the intrinsic color distributions. This new method remains computationally competitive, making it possible to correctly de-redden millions of sources within a matter of seconds. With the ever-increasing number of large-scale high-sensitivity imaging surveys, Pnicer offers a fast and reliable way to efficiently calculate extinction for arbitrary parameter combinations without prior information on source characteristics. The Pnicer software package also offers access to the well-established Nicer technique in a simple unified interface and is capable of building extinction maps including the Nicest correction for cloud substructure. Pnicer is offered to the community as an open-source software solution and is entirely written in Python.

  9. The endocannabinoid system and extinction learning.

    PubMed

    Lutz, Beat

    2007-08-01

    The endocannabinoid system has emerged as a versatile neuromodulatory system, implicated in a plethora of physiological and pathophysiological processes. Cannabinoid receptor type 1 (CB1 receptor) and endocannabinoids are widely distributed in the brain. Their roles in learning and memory have been well documented, using rodents in various memory tests. Depending on the test, the endocannabinoid system is required in the acquisition and/or extinction of memory. In particular, the activation of CB1 receptor-mediated signaling is centrally involved in the facilitation of behavioral adaptation after the acquisition of aversive memories. As several human psychiatric disorders, such as phobia, generalized anxiety disorders, and posttraumatic stress disorder (PTSD) appear to involve aberrant memory processing and impaired adaptation to changed environmental conditions, the hope has been fuelled that the endocannabinoid system might be a valuable therapeutic target for the treatment of these disorders. This review summarizes the current data on the role of the endocannabinoid system in the modulation of extinction learning.

  10. Vicarious extinction learning during reconsolidation neutralizes fear memory.

    PubMed

    Golkar, Armita; Tjaden, Cathelijn; Kindt, Merel

    2017-05-01

    Previous studies have suggested that fear memories can be updated when recalled, a process referred to as reconsolidation. Given the beneficial effects of model-based safety learning (i.e. vicarious extinction) in preventing the recovery of short-term fear memory, we examined whether consolidated long-term fear memories could be updated with safety learning accomplished through vicarious extinction learning initiated within the reconsolidation time-window. We assessed this in a final sample of 19 participants that underwent a three-day within-subject fear-conditioning design, using fear-potentiated startle as our primary index of fear learning. On day 1, two fear-relevant stimuli (reinforced CSs) were paired with shock (US) and a third stimulus served as a control (CS). On day 2, one of the two previously reinforced stimuli (the reminded CS) was presented once in order to reactivate the fear memory 10 min before vicarious extinction training was initiated for all CSs. The recovery of the fear memory was tested 24 h later. Vicarious extinction training conducted within the reconsolidation time window specifically prevented the recovery of the reactivated fear memory (p = 0.03), while leaving fear-potentiated startle responses to the non-reactivated cue intact (p = 0.62). These findings are relevant to both basic and clinical research, suggesting that a safe, non-invasive model-based exposure technique has the potential to enhance the efficiency and durability of anxiolytic therapies. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. d-Cycloserine facilitates extinction learning and enhances extinction-related brain activation.

    PubMed

    Klass, Anne; Glaubitz, Benjamin; Tegenthoff, Martin; Lissek, Silke

    2017-10-01

    Extinction learning is modulated by N-methyl d-aspartate receptors (NMDAR) particularly in prefrontal and hippocampal brain regions. The use of of NMDA agonists in exposure therapy of anxiety disorders has been investigated in various patient groups. Behavioral results showed beneficial effects of pre-learning administration of the partial NMDAR agonist d-Cycloserine (DCS) on therapy success. However, the impact of DCS upon non-fear-related contextual extinction, and associated recruitment of extinction-relevant brain regions is as yet unknown. In the present fMRI study, healthy human participants performed a context-related associative learning and extinction task. A single dose of DCS, administered prior to extinction learning, enhanced extinction learning performance in an identical context, and increased activation in prefrontal, temporal as well as hippocampal/insular regions, compared to placebo controls. In contrast, DCS did not affect extinction learning in a novel context, nor the renewal effect, which describes the recovery of an extinguished response if the context of extinction differs from the context of recall. Our findings demonstrate a specific involvement of prefrontal and hippocampal NMDAR in the modification of established stimulus-outcome associations in identical contexts and thus their role in behavioral flexibility, underlining their potential for enhancing AAA extinction learning. Copyright © 2017. Published by Elsevier Inc.

  12. Slower Reacquisition after Partial Extinction in Human Contingency Learning

    ERIC Educational Resources Information Center

    Morís, Joaquín; Barberia, Itxaso; Vadillo, Miguel A.; Andrades, Ainhoa; López, Francisco J.

    2017-01-01

    Extinction is a very relevant learning phenomenon from a theoretical and applied point of view. One of its most relevant features is that relapse phenomena often take place once the extinction training has been completed. Accordingly, as extinction-based therapies constitute the most widespread empirically validated treatment of anxiety disorders,…

  13. Slower Reacquisition after Partial Extinction in Human Contingency Learning

    ERIC Educational Resources Information Center

    Morís, Joaquín; Barberia, Itxaso; Vadillo, Miguel A.; Andrades, Ainhoa; López, Francisco J.

    2017-01-01

    Extinction is a very relevant learning phenomenon from a theoretical and applied point of view. One of its most relevant features is that relapse phenomena often take place once the extinction training has been completed. Accordingly, as extinction-based therapies constitute the most widespread empirically validated treatment of anxiety disorders,…

  14. Extinction of Learned Fear Induces Hippocampal Place Cell Remapping

    PubMed Central

    Wang, Melissa E.; Yuan, Robin K.; Keinath, Alexander T.; Ramos Álvarez, Manuel M.

    2015-01-01

    The extinction of learned fear is a hippocampus-dependent process thought to embody new learning rather than erasure of the original fear memory, although it is unknown how these competing contextual memories are represented in the hippocampus. We previously demonstrated that contextual fear conditioning results in hippocampal place cell remapping and long-term stabilization of novel representations. Here we report that extinction learning also induces place cell remapping in C57BL/6 mice. Specifically, we observed cells that preferentially remapped during different stages of learning. While some cells remapped in both fear conditioning and extinction, others responded predominantly during extinction, which may serve to modify previous representations as well as encode new safe associations. Additionally, we found cells that remapped primarily during fear conditioning, which could facilitate reacquisition of the original fear association. Moreover, we also observed cells that were stable throughout learning, which may serve to encode the static aspects of the environment. The short-term remapping observed during extinction was not found in animals that did not undergo fear conditioning, or when extinction was conducted outside of the conditioning context. Finally, conditioning and extinction produced an increase in spike phase locking to the theta and gamma frequencies. However, the degree of remapping seen during conditioning and extinction only correlated with gamma synchronization. Our results suggest that the extinction learning is a complex process that involves both modification of pre-existing memories and formation of new ones, and these traces coexist within the same hippocampal representation. PMID:26085635

  15. Extinction of Learned Fear Induces Hippocampal Place Cell Remapping.

    PubMed

    Wang, Melissa E; Yuan, Robin K; Keinath, Alexander T; Ramos Álvarez, Manuel M; Muzzio, Isabel A

    2015-06-17

    The extinction of learned fear is a hippocampus-dependent process thought to embody new learning rather than erasure of the original fear memory, although it is unknown how these competing contextual memories are represented in the hippocampus. We previously demonstrated that contextual fear conditioning results in hippocampal place cell remapping and long-term stabilization of novel representations. Here we report that extinction learning also induces place cell remapping in C57BL/6 mice. Specifically, we observed cells that preferentially remapped during different stages of learning. While some cells remapped in both fear conditioning and extinction, others responded predominantly during extinction, which may serve to modify previous representations as well as encode new safe associations. Additionally, we found cells that remapped primarily during fear conditioning, which could facilitate reacquisition of the original fear association. Moreover, we also observed cells that were stable throughout learning, which may serve to encode the static aspects of the environment. The short-term remapping observed during extinction was not found in animals that did not undergo fear conditioning, or when extinction was conducted outside of the conditioning context. Finally, conditioning and extinction produced an increase in spike phase locking to the theta and gamma frequencies. However, the degree of remapping seen during conditioning and extinction only correlated with gamma synchronization. Our results suggest that the extinction learning is a complex process that involves both modification of pre-existing memories and formation of new ones, and these traces coexist within the same hippocampal representation.

  16. Cerebellar Contribution to Context Processing in Extinction Learning and Recall.

    PubMed

    Chang, D-I; Lissek, S; Ernst, T M; Thürling, M; Uengoer, M; Tegenthoff, M; Ladd, M E; Timmann, D

    2015-12-01

    Whereas acquisition of new associations is considered largely independent of the context, context dependency is a hallmark of extinction of the learned associations. The hippocampus and the prefrontal cortex are known to be involved in context processing during extinction learning and recall. Although the cerebellum has known functional and anatomic connections to the hippocampus and the prefrontal cortex, cerebellar contributions to context processing of extinction have rarely been studied. In the present study, we reanalyzed functional brain imaging data (fMRI) of previous work investigating context effects during extinction in a cognitive associative learning paradigm in 28 young and healthy subjects (Lissek et al. Neuroimage. 81:131-3, 2013). In that study, event-related fMRI analysis did not include the cerebellum. The 3 T fMRI dataset was reanalyzed using a spatial normalization method optimized for the cerebellum. Data of seven participants had to be excluded because the cerebellum had not been scanned in full. Cerebellar activation related to context change during extinction learning was most prominent in lobule Crus II bilaterally (p < 0.01, t > 2.53; partially corrected by predetermined cluster size). No significant cerebellar activations were observed related to context change during extinction retrieval. The posterolateral cerebellum appears to contribute to context-related processes during extinction learning, but not (or less) during extinction retrieval. The cerebellum may support context learning during extinction via its connections to the hippocampus. Alternatively, the cerebellum may support the shifting of attention to the context via its known connections to the dorsolateral prefrontal cortex. Because the ventromedial prefrontal cortex (vmPFC) is critically involved in context-related processes during extinction retrieval, and there are no known connections between the cerebellum and the vmPFC, the cerebellum may be less important

  17. Adrenal-dependent diurnal modulation of conditioned fear extinction learning

    PubMed Central

    Woodruff, Elizabeth R.; Greenwood, Benjamin N.; Chun, Lauren E.; Fardi, Sara; Hinds, Laura R.; Spencer, Robert L.

    2015-01-01

    Post Traumatic Stress Disorder (PTSD) is associated with altered conditioned fear extinction expression and impaired circadian function including dysregulation of glucocorticoid hormone secretion. We examined in adult male rats the relationship between conditioned fear extinction learning, circadian phase, and endogenous glucocorticoids (CORT). Rats maintained on a 12 hr light:dark cycle were trained and tested across 3 separate daily sessions (conditioned fear acquisition and 2 extinction sessions) that were administered during either the rats’ active or inactive circadian phase. In an initial experiment we found that rats at both circadian phases acquired and extinguished auditory cue conditioned fear to a similar degree in the first extinction session. However, rats trained and tested at zeitgeber time-16 (ZT16) (active phase) showed enhanced extinction memory expression during the second extinction session compared to rats trained and tested at ZT4 (inactive phase). In a follow-up experiment, adrenalectomized (ADX) or sham surgery rats were similarly trained and tested across 3 separate daily sessions at either ZT4 or ZT16. ADX had no effect on conditioned fear acquisition or conditioned fear memory. Sham ADX rats trained and tested at ZT16 exhibited better extinction learning across the two extinction sessions compared to all other groups of rats. These results indicate that conditioned fear extinction learning is modulated by time of day, and this diurnal modulation requires the presence of adrenal hormones. These results support an important role of CORT-dependent circadian processes in regulating conditioned fear extinction learning, which may be capitalized upon to optimize effective treatment of PTSD. PMID:25746455

  18. Adrenal-dependent diurnal modulation of conditioned fear extinction learning.

    PubMed

    Woodruff, Elizabeth R; Greenwood, Benjamin N; Chun, Lauren E; Fardi, Sara; Hinds, Laura R; Spencer, Robert L

    2015-06-01

    Post traumatic stress disorder (PTSD) is associated with altered conditioned fear extinction expression and impaired circadian function including dysregulation of glucocorticoid hormone secretion. We examined in adult male rats the relationship between conditioned fear extinction learning, circadian phase, and endogenous glucocorticoids (CORT). Rats maintained on a 12h light:dark cycle were trained and tested across 3 separate daily sessions (conditioned fear acquisition and 2 extinction sessions) that were administered during either the rats' active or inactive circadian phase. In an initial experiment we found that rats at both circadian phases acquired and extinguished auditory cue conditioned fear to a similar degree in the first extinction session. However, rats trained and tested at zeitgeber time-16 (ZT16) (active phase) showed enhanced extinction memory expression during the second extinction session compared to rats trained and tested at ZT4 (inactive phase). In a follow-up experiment, adrenalectomized (ADX) or sham surgery rats were similarly trained and tested across 3 separate daily sessions at either ZT4 or ZT16. ADX had no effect on conditioned fear acquisition or conditioned fear memory. Sham ADX rats trained and tested at ZT16 exhibited better extinction learning across the two extinction sessions compared to all other groups of rats. These results indicate that conditioned fear extinction learning is modulated by time of day, and this diurnal modulation requires the presence of adrenal hormones. These results support an important role of CORT-dependent circadian processes in regulating conditioned fear extinction learning, which may be capitalized upon to optimize effective treatment of PTSD.

  19. 3,4-Methylenedioxymethamphetamine facilitates fear extinction learning.

    PubMed

    Young, M B; Andero, R; Ressler, K J; Howell, L L

    2015-09-15

    Acutely administered 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') has been proposed to have long-term positive effects on post-traumatic stress disorder (PTSD) symptoms when combined with psychotherapy. No preclinical data support a mechanistic basis for these claims. Given the persistent nature of psychotherapeutic gains facilitated by MDMA, we hypothesized that MDMA improves fear extinction learning, a key process in exposure-based therapies for PTSD. In these experiments, mice were first exposed to cued fear conditioning and treated with drug vehicle or MDMA before extinction training 2 days later. MDMA was administered systemically and also directly targeted to brain structures known to contribute to extinction. In addition to behavioral measures of extinction, changes in mRNA levels of brain-derived neurotrophic factor (Bdnf) and Fos were measured after MDMA treatment and extinction. MDMA (7.8 mg kg(-1)) persistently and robustly enhanced long-term extinction when administered before extinction training. MDMA increased the expression of Fos in the amygdala and medial prefrontal cortex (mPFC), whereas increases in Bdnf expression were observed only in the amygdala after extinction training. Extinction enhancements were recapitulated when MDMA (1 μg) was infused directly into the basolateral complex of the amygdala (BLA), and enhancement was abolished when BDNF signaling was inhibited before extinction. These findings suggest that MDMA enhances fear memory extinction through a BDNF-dependent mechanism, and that MDMA may be a useful adjunct to exposure-based therapies for PTSD and other anxiety disorders characterized by altered fear learning.

  20. 3,4-Methylenedioxymethamphetamine facilitates fear extinction learning

    PubMed Central

    Young, M B; Andero, R; Ressler, K J; Howell, L L

    2015-01-01

    Acutely administered 3,4-methylenedioxymethamphetamine (MDMA, ‘ecstasy') has been proposed to have long-term positive effects on post-traumatic stress disorder (PTSD) symptoms when combined with psychotherapy. No preclinical data support a mechanistic basis for these claims. Given the persistent nature of psychotherapeutic gains facilitated by MDMA, we hypothesized that MDMA improves fear extinction learning, a key process in exposure-based therapies for PTSD. In these experiments, mice were first exposed to cued fear conditioning and treated with drug vehicle or MDMA before extinction training 2 days later. MDMA was administered systemically and also directly targeted to brain structures known to contribute to extinction. In addition to behavioral measures of extinction, changes in mRNA levels of brain-derived neurotrophic factor (Bdnf) and Fos were measured after MDMA treatment and extinction. MDMA (7.8 mg kg−1) persistently and robustly enhanced long-term extinction when administered before extinction training. MDMA increased the expression of Fos in the amygdala and medial prefrontal cortex (mPFC), whereas increases in Bdnf expression were observed only in the amygdala after extinction training. Extinction enhancements were recapitulated when MDMA (1  μg) was infused directly into the basolateral complex of the amygdala (BLA), and enhancement was abolished when BDNF signaling was inhibited before extinction. These findings suggest that MDMA enhances fear memory extinction through a BDNF-dependent mechanism, and that MDMA may be a useful adjunct to exposure-based therapies for PTSD and other anxiety disorders characterized by altered fear learning. PMID:26371762

  1. Behavioral and neural bases of extinction learning in Hermissenda

    PubMed Central

    Cavallo, Joel S.; Hamilton, Brittany N.; Farley, Joseph

    2014-01-01

    Extinction of classical conditioning is thought to produce new learning that masks or interferes with the original memory. However, research in the nudibranch Hermissenda crassicornis (H.c.) has challenged this view, and instead suggested that extinction erased the original associative memory. We have re-examined extinction in H.c. to test whether extinguished associative memories can be detected on the behavioral and cellular levels, and to characterize the temporal variables involved. Associative conditioning using pairings of light (CS) and rotation (US) produced characteristic suppression of H.c. phototactic behavior. A single session of extinction training (repeated light-alone presentations) reversed suppressed behavior back to pre-training levels when administered 15 min after associative conditioning. This effect was abolished if extinction was delayed by 23 h, and yet was recovered using extended extinction training (three consecutive daily extinction sessions). Extinguished phototactic suppression did not spontaneously recover at any retention interval (RI) tested (2-, 24-, 48-, 72-h), or after additional US presentations (no observed reinstatement). Extinction training (single session, 15 min interval) also reversed the pairing-produced increases in light-evoked spike frequencies of Type B photoreceptors, an identified site of associative memory storage that is causally related to phototactic suppression. These results suggest that the behavioral effects of extinction training are not due to temporary suppression of associative memories, but instead represent a reversal of the underlying cellular changes necessary for the expression of learning. In the companion article, we further elucidate mechanisms responsible for extinction-produced reversal of memory-related neural plasticity in Type B photoreceptors. PMID:25191236

  2. d-Cycloserine reduces context specificity of sexual extinction learning.

    PubMed

    Brom, Mirte; Laan, Ellen; Everaerd, Walter; Spinhoven, Philip; Trimbos, Baptist; Both, Stephanie

    2015-11-01

    d-Cycloserine (DCS) enhances extinction processes in animals. Although classical conditioning is hypothesized to play a pivotal role in the aetiology of appetitive motivation problems, no research has been conducted on the effect of DCS on the reduction of context specificity of extinction in human appetitive learning, while facilitation hereof is relevant in the context of treatment of problematic reward-seeking behaviors. Female participants were presented with two conditioned stimuli (CSs) that either predicted (CS+) or did not predict (CS-) a potential sexual reward (unconditioned stimulus (US); genital vibrostimulation). Conditioning took place in context A and extinction in context B. Subjects received DCS (125mg) or placebo directly after the experiment on day 1 in a randomized, double-blind, between-subject fashion (Placebo n=31; DCS n=31). Subsequent testing for CS-evoked conditioned responses (CRs) in both the conditioning (A) and the extinction context (B) took place 24h later on day 2. Drug effects on consolidation were then assessed by comparing the recall of sexual extinction memories between the DCS and the placebo groups. Post learning administration of DCS facilitates sexual extinction memory consolidation and affects extinction's fundamental context specificity, evidenced by reduced conditioned genital and subjective sexual responses, relative to placebo, for presentations of the reward predicting cue 24h later outside the extinction context. DCS makes appetitive extinction memories context-independent and prevents the return of conditioned response. NMDA receptor glycine site agonists may be potential pharmacotherapies for the prevention of relapse of appetitive motivation disorders with a learned component. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Environmental Learning and the Study of Extinction.

    ERIC Educational Resources Information Center

    Bell, Anne C.; Russell, Constance L.; Plotkin, Rachel

    1998-01-01

    Describes an environmental workshop with three goals: (1) to develop a more grounded and personal understanding in students of extinction; (2) to draw attention to their specific life contexts while making connections between local and global phenomena; and (3) to critically examine anthropocentrism. Highlights efforts to disrupt strictly…

  4. Extinction learning, reconsolidation and the internal reinforcement hypothesis.

    PubMed

    Eisenhardt, Dorothea; Menzel, Randolf

    2007-02-01

    Retrieving a consolidated memory--by exposing an animal to the learned stimulus but not to the associated reinforcement--leads to two opposing processes: one that weakens the old memory as a result of extinction learning, and another that strengthens the old, already-consolidated memory as a result of some less well-understood form of learning. This latter process of memory strengthening is often referred to as "reconsolidation", since protein synthesis can inhibit this form of memory formation. Although the behavioral phenomena of the two antagonizing forms of learning are well documented, the mechanisms behind the corresponding processes of memory formation are still quite controversial. Referring to results of extinction/reconsolidation experiments in honeybees, we argue that two opposing learning processes--with their respective consolidation phases and memories--are initiated by retrieval trials: extinction learning and reminder learning, the latter leading to the phenomenon of spontaneous recovery from extinction, a process that can be blocked with protein synthesis inhibition.

  5. Caloric restriction enhances fear extinction learning in mice.

    PubMed

    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.

  6. Instructed fear learning, extinction, and recall: additive effects of cognitive information on emotional learning of fear.

    PubMed

    Javanbakht, Arash; Duval, Elizabeth R; Cisneros, Maria E; Taylor, Stephan F; Kessler, Daniel; Liberzon, Israel

    2017-08-01

    The effects of instruction on learning of fear and safety are rarely studied. We aimed to examine the effects of cognitive information and experience on fear learning. Fourty healthy participants, randomly assigned to three groups, went through fear conditioning, extinction learning, and extinction recall with two conditioned stimuli (CS+). Information was presented about the presence or absence of conditioned stimulus-unconditioned stimulus (CS-US) contingency at different stages of the experiment. Information about the CS-US contingency prior to fear conditioning enhanced fear response and reduced extinction recall. Information about the absence of CS-US contingency promoted extinction learning and recall, while omission of this information prior to recall resulted in fear renewal. These findings indicate that contingency information can facilitate fear expression during fear learning, and can facilitate extinction learning and recall. Information seems to function as an element of the larger context in which conditioning occurs.

  7. Cellular and oscillatory substrates of fear extinction learning.

    PubMed

    Davis, Patrick; Zaki, Yosif; Maguire, Jamie; Reijmers, Leon G

    2017-10-02

    The mammalian brain contains dedicated circuits for both the learned expression and suppression of fear. These circuits require precise coordination to facilitate the appropriate expression of fear behavior, but the mechanisms underlying this coordination remain unclear. Using a combination of chemogenetics, activity-based neuronal-ensemble labeling and in vivo electrophysiology, we found that fear extinction learning confers on parvalbumin-expressing (PV) interneurons in the basolateral amygdala (BLA) a dedicated role in the selective suppression of a previously encoded fear memory and BLA fear-encoding neurons. In addition, following extinction learning, PV interneurons enable a competing interaction between a 6-12 Hz oscillation and a fear-associated 3-6 Hz oscillation within the BLA. Loss of this competition increases a 3-6 Hz oscillatory signature, with BLA→medial prefrontal cortex directionality signaling the recurrence of fear expression. The discovery of cellular and oscillatory substrates of fear extinction learning that critically depend on BLA PV interneurons could inform therapies aimed at preventing the pathological recurrence of fear following extinction learning.

  8. Reconciling Reinforcement Learning Models with Behavioral Extinction and Renewal: Implications for Addiction, Relapse, and Problem Gambling

    ERIC Educational Resources Information Center

    Redish, A. David; Jensen, Steve; Johnson, Adam; Kurth-Nelson, Zeb

    2007-01-01

    Because learned associations are quickly renewed following extinction, the extinction process must include processes other than unlearning. However, reinforcement learning models, such as the temporal difference reinforcement learning (TDRL) model, treat extinction as an unlearning of associated value and are thus unable to capture renewal. TDRL…

  9. The Effect of D-Cycloserine on Immediate vs. Delayed Extinction of Learned Fear

    ERIC Educational Resources Information Center

    Langton, Julia M.; Richardson, Rick

    2010-01-01

    We compared the effect of D-cycloserine (DCS) on immediate (10 min after conditioning) and delayed (24 h after conditioning) extinction of learned fear in rats. DCS facilitated both immediate and delayed extinction when the drug was administered after extinction training. However, DCS did not facilitate immediate extinction when administered prior…

  10. The Effect of D-Cycloserine on Immediate vs. Delayed Extinction of Learned Fear

    ERIC Educational Resources Information Center

    Langton, Julia M.; Richardson, Rick

    2010-01-01

    We compared the effect of D-cycloserine (DCS) on immediate (10 min after conditioning) and delayed (24 h after conditioning) extinction of learned fear in rats. DCS facilitated both immediate and delayed extinction when the drug was administered after extinction training. However, DCS did not facilitate immediate extinction when administered prior…

  11. A requirement for memory retrieval during and after long-term extinction learning.

    PubMed

    Ouyang, Ming; Thomas, Steven A

    2005-06-28

    Current learning theories are based on the idea that learning is driven by the difference between expectations and experience (the delta rule). In extinction, one learns that certain expectations no longer apply. Here, we test the potential validity of the delta rule by manipulating memory retrieval (and thus expectations) during extinction learning. Adrenergic signaling is critical for the time-limited retrieval (but not acquisition or consolidation) of contextual fear. Using genetic and pharmacologic approaches to manipulate adrenergic signaling, we find that long-term extinction requires memory retrieval but not conditioned responding. Identical manipulations of the adrenergic system that do not affect memory retrieval do not alter extinction. The results provide substantial support for the delta rule of learning theory. In addition, the timing over which extinction is sensitive to adrenergic manipulation suggests a model whereby memory retrieval occurs during, and several hours after, extinction learning to consolidate long-term extinction memory.

  12. Noradrenergic stimulation modulates activation of extinction-related brain regions and enhances contextual extinction learning without affecting renewal

    PubMed Central

    Lissek, Silke; Glaubitz, Benjamin; Güntürkün, Onur; Tegenthoff, Martin

    2015-01-01

    Renewal in extinction learning describes the recovery of an extinguished response if the extinction context differs from the context present during acquisition and recall. Attention may have a role in contextual modulation of behavior and contribute to the renewal effect, while noradrenaline (NA) is involved in attentional processing. In this functional magnetic resonance imaging (fMRI) study we investigated the role of the noradrenergic system for behavioral and brain activation correlates of contextual extinction and renewal, with a particular focus upon hippocampus and ventromedial prefrontal cortex (PFC), which have crucial roles in processing of renewal. Healthy human volunteers received a single dose of the NA reuptake inhibitor atomoxetine prior to extinction learning. During extinction of previously acquired cue-outcome associations, cues were presented in a novel context (ABA) or in the acquisition context (AAA). In recall, all cues were again presented in the acquisition context. Atomoxetine participants (ATO) showed significantly faster extinction compared to placebo (PLAC). However, atomoxetine did not affect renewal. Hippocampal activation was higher in ATO during extinction and recall, as was ventromedial PFC activation, except for ABA recall. Moreover, ATO showed stronger recruitment of insula, anterior cingulate, and dorsolateral/orbitofrontal PFC. Across groups, cingulate, hippocampus and vmPFC activity during ABA extinction correlated with recall performance, suggesting high relevance of these regions for processing the renewal effect. In summary, the noradrenergic system appears to be involved in the modification of established associations during extinction learning and thus has a role in behavioral flexibility. The assignment of an association to a context and the subsequent decision on an adequate response, however, presumably operate largely independently of noradrenergic mechanisms. PMID:25745389

  13. Sex differences in learned fear expression and extinction involve altered gamma oscillations in medial prefrontal cortex.

    PubMed

    Fenton, Georgina E; Halliday, David M; Mason, Rob; Bredy, Timothy W; Stevenson, Carl W

    2016-11-01

    Sex differences in learned fear expression and extinction involve the medial prefrontal cortex (mPFC). We recently demonstrated that enhanced learned fear expression during auditory fear extinction and its recall is linked to persistent theta activation in the prelimbic (PL) but not infralimbic (IL) cortex of female rats. Emerging evidence indicates that gamma oscillations in mPFC are also implicated in the expression and extinction of learned fear. Therefore we re-examined our in vivo electrophysiology data and found that females showed persistent PL gamma activation during extinction and a failure of IL gamma activation during extinction recall. Altered prefrontal gamma oscillations thus accompany sex differences in learned fear expression and its extinction. These findings are relevant for understanding the neural basis of post-traumatic stress disorder, which is more prevalent in women and involves impaired extinction and mPFC dysfunction.

  14. Stress-enhanced fear learning in rats is resistant to the effects of immediate massed extinction.

    PubMed

    Long, Virginia A; Fanselow, Michael S

    2012-11-01

    Enhanced fear learning occurs subsequent to traumatic or stressful events and is a persistent challenge to the treatment of post-traumatic stress disorder (PTSD). Facilitation of learning produced by prior stress can elicit an exaggerated fear response to a minimally aversive event or stimulus. Stress-enhanced fear learning (SEFL) is a rat model of PTSD; rats previously exposed to the SEFL 15 electrical shocks procedure exhibit several behavioral responses similar to those seen in patients with PTSD. However, past reports found that SEFL is not mitigated by extinction (a model of exposure therapy) when the spaced extinction began 24 h after stress. Recent studies found that extinction from 10 min to 1 h subsequent to fear conditioning "erased" learning, whereas later extinction, occurring from 24 to 72 h after conditioning did not. Other studies indicate that massed extinction is more effective than spaced procedures. Therefore, we examined the time-dependent nature of extinction on the stress-induced enhancement of fear learning using a massed trial's procedure. Experimental rats received 15 foot shocks and were given either no extinction or massed extinction 10 min or 72 h later. Our present data indicate that SEFL, following traumatic stress, is resistant to immediate massed extinction. Experimental rats showed exaggerated new fear learning regardless of when extinction training occurred. Thus, post-traumatic reactivity such as SEFL does not seem responsive to extinction treatments.

  15. Stress-enhanced fear learning in rats is resistant to the effects of immediate massed extinction

    PubMed Central

    Long, Virginia A.; Fanselow, Michael S.

    2014-01-01

    Enhanced fear learning occurs subsequent to traumatic or stressful events and is a persistent challenge to the treatment of post-traumatic stress disorder (PTSD). Facilitation of learning produced by prior stress can elicit an exaggerated fear response to a minimally aversive event or stimulus. Stress-enhanced fear learning (SEFL) is a rat model of PTSD; rats previously exposed to the SEFL 15 electrical shocks procedure exhibit several behavioral responses similar to those seen in patients with PTSD. However, past reports found that SEFL is not mitigated by extinction (a model of exposure therapy) when the spaced extinction began 24 h after stress. Recent studies found that extinction from 10 min to 1 h subsequent to fear conditioning “erased” learning, whereas later extinction, occurring from 24 to 72 h after conditioning did not. Other studies indicate that massed extinction is more effective than spaced procedures. Therefore, we examined the time-dependent nature of extinction on the stress-induced enhancement of fear learning using a massed trial’s procedure. Experimental rats received 15 foot shocks and were given either no extinction or massed extinction 10 min or 72 h later. Our present data indicate that SEFL, following traumatic stress, is resistant to immediate massed extinction. Experimental rats showed exaggerated new fear learning regardless of when extinction training occurred. Thus, post-traumatic reactivity such as SEFL does not seem responsive to extinction treatments. PMID:22176467

  16. Relapse processes after the extinction of instrumental learning: Renewal, resurgence, and reacquisition

    PubMed Central

    Bouton, Mark E.; Winterbauer, Neil E.; Todd, Travis P.

    2012-01-01

    It is widely recognized that extinction (the procedure in which a Pavlovian conditioned stimulus or an instrumental action is repeatedly presented without its reinforcer) weakens behavior without erasing the original learning. Most of the experiments that support this claim have focused on several “relapse” effects that occur after Pavlovian extinction, which collectively suggest that the original learning is saved through extinction. However, although such effects do occur after instrumental extinction, they have not been explored there in as much detail. This article reviews recent research in our laboratory that has investigated three relapse effects that occur after the extinction of instrumental (operant) learning. In renewal, responding returns after extinction when the behavior is tested in a different context; in resurgence, responding recovers when a second response that has been reinforced during extinction of the first is itself put on extinction; and in rapid reacquisition, extinguished responding returns rapidly when the response is reinforced again. The results provide new insights into extinction and relapse, and are consistent with principles that have been developed to explain extinction and relapse as they occur after Pavlovian conditioning. Extinction of instrumental learning, like Pavlovian learning, involves new learning that is relatively dependent on the context for expression. PMID:22450305

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

    ERIC Educational Resources Information Center

    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.…

  18. Effects of D-cycloserine on the extinction of appetitive operant learning.

    PubMed

    Vurbic, Drina; Gold, Benjamin; Bouton, Mark E

    2011-08-01

    Four experiments with rat subjects examined whether D-cycloserine (DCS), a partial NMDA agonist, facilitates the extinction of operant lever-pressing reinforced by food. Previous research has demonstrated that DCS facilitates extinction learning with methods that involve Pavlovian extinction. In the current experiments, operant conditioning occurred in Context A, extinction in Context B, and then testing occurred in both the extinction and conditioning contexts. Experiments 1A and 1B tested the effects of three doses of DCS (5, 15, and 30 mg/kg) on the extinction of lever pressing trained as a free operant. Experiment 2 examined their effects when extinction of the free operant was conducted in the presence of nonresponse-contingent deliveries of the reinforcer (that theoretically reduced the role of generalization decrement in suppressing responding). Experiment 3 examined their effects on extinction of a discriminated operant, that is, one that had been reinforced in the presence of a discriminative stimulus, but not in its absence. A strong ABA renewal effect was observed in all four experiments during testing. However, despite the use of DCS doses and a drug administration procedure that facilitates the extinction of Pavlovian learning, there was no evidence in any experiment that DCS facilitated operant extinction learning assessed in either the extinction or the conditioning context. DCS may primarily facilitate learning processes that underlie Pavlovian, rather than purely operant, extinction. (PsycINFO Database Record (c) 2011 APA, all rights reserved).

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

    ERIC Educational Resources Information Center

    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.…

  20. No evidence for blocking the return of fear by disrupting reconsolidation prior to extinction learning.

    PubMed

    Klucken, Tim; Kruse, Onno; Schweckendiek, Jan; Kuepper, Yvonne; Mueller, Erik M; Hennig, Juergen; Stark, Rudolf

    2016-06-01

    Fear extinction is a central model for the treatment of anxiety disorders. Initial research has reported that the single presentation of a conditioned stimulus prior to extinction learning can permanently block the return of fear. However, only few studies have explored this issue and could not always replicate the findings. The present study examined human fear extinction using a four-day design. On the first day, two neutral stimuli were paired with electrical stimulation (UCS), while a third stimulus (CS-) was not. Twenty-four hours later, one conditioned stimulus (CS+rem) and the CS- were reminded once, 10 min before extinction learning, while the other conditioned stimulus (CS+non-rem) was not presented prior to extinction learning. All stimuli were presented during extinction learning and during two re-extinction sessions (24 h and 6-months after extinction learning) without reinforcement. Blood oxygen level-dependent (BOLD) responses and skin conductance responses (SCRs) to both CS+ and the CS- were explored during acquisition, extinction, and in both re-extinction sessions. Regarding SCRs, the results showed that a single presentation of a conditioned stimulus did not block the return of fear during re-extinction: Fear recovery during re-extinction (24 h and 6-months after extinction learning) was observed for both CS+ compared with the CS- with no difference between CS+rem and CS+non-rem. Regarding BOLD-responses, no significant differences between CS+rem and CS+non-rem were found in region of interest (ROI)-analyses (amygdala, ventromedial prefrontal cortex) during extinction learning and both re-extinction sessions. Whole-brain analyses showed increased BOLD-responses to the CS+non-rem as compared to the CS+rem in several regions (e.g., middle frontal gyrus) during extinction learning and re-extinction (24 h after extinction learning). The present findings suggest that the effect of preventing the return of fear by disrupting reconsolidation seems to

  1. mGluR5 Positive Allosteric Modulation Enhances Extinction Learning Following Cocaine Self-Administration

    PubMed Central

    Cleva, Richard M.; Hicks, Megan P.; Gass, Justin T.; Wischerath, Kelly C.; Plasters, Elizabeth T.; Widholm, John J.; Olive, M. Foster

    2011-01-01

    Extinction of classically and instrumentally conditioned behaviors, such as conditioned fear and drug-seeking behavior, is a process of active learning, and recent studies indicate that potentiation of glutamatergic transmission facilitates extinction learning. In this study we investigated the effects of the type 5 metabotropic glutamate receptors (mGluR5) positive allosteric modulator 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide (CDPPB) on the extinction of cocaine-seeking behavior in rats with a history of intravenous cocaine self-administration. To assess its effects on acquisition and consolidation of extinction learning, CDPPB (60 mg/kg) or vehicle was administered either 20 min prior to, or immediately following, each of 10 extinction sessions, respectively. When administered prior to each extinction session, CDPPB produced a significant reduction in the number of active lever presses on all 10 days of extinction training as compared to vehicle-treated animals. When administered following each extinction session, a significant reduction in the number of active lever presses was observed on the 2nd through 10th day of extinction. Both treatment regimens also reduced the number of extinction training sessions required to meet extinction criteria. Pre- or post-extinction training administration of CDPPB did not alter responding on the inactive lever and had no effects on open field locomotor activity. These data indicate that positive allosteric modulation of mGluR5 receptors facilitates the acquisition and consolidation of extinction learning following cocaine self-administration, and may provide a novel pharmacological approach to enhancing extinction learning when combined with cue exposure therapy for the treatment of cocaine addiction. PMID:21319882

  2. Compound Stimulus Presentation Does Not Deepen Extinction in Human Causal Learning

    PubMed Central

    Griffiths, Oren; Holmes, Nathan; Westbrook, R. Fred

    2017-01-01

    Models of associative learning have proposed that cue-outcome learning critically depends on the degree of prediction error encountered during training. Two experiments examined the role of error-driven extinction learning in a human causal learning task. Target cues underwent extinction in the presence of additional cues, which differed in the degree to which they predicted the outcome, thereby manipulating outcome expectancy and, in the absence of any change in reinforcement, prediction error. These prediction error manipulations have each been shown to modulate extinction learning in aversive conditioning studies. While both manipulations resulted in increased prediction error during training, neither enhanced extinction in the present human learning task (one manipulation resulted in less extinction at test). The results are discussed with reference to the types of associations that are regulated by prediction error, the types of error terms involved in their regulation, and how these interact with parameters involved in training. PMID:28232809

  3. Impaired fear extinction learning and cortico-amygdala circuit abnormalities in a common genetic mouse strain.

    PubMed

    Hefner, Kathryn; Whittle, Nigel; Juhasz, Jaynann; Norcross, Maxine; Karlsson, Rose-Marie; Saksida, Lisa M; Bussey, Timothy J; Singewald, Nicolas; Holmes, Andrew

    2008-08-06

    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 C57BL/6J for one-trial and multitrial fear conditioning, nociception, and extinction of conditioned taste aversion and an appetitive instrumental response. 129S1 were tested for sensitivity to the extinction-facilitating effects of extended training, as well as d-cycloserine and yohimbine treatment. To elucidate the neural basis of impaired 129S1 fear extinction, c-Fos and Zif268 expression was mapped after extinction recall. Results showed that impaired fear extinction in 129S1 was unrelated to altered fear conditioning or nociception, and was dissociable from intact appetitive extinction. Yohimbine treatment facilitated extinction in 129S1, but neither extended extinction training nor d-cycloserine treatment improved 129S1 extinction. After extinction recall, 129S1 showed reduced c-Fos and Zif268 expression in the infralimbic cortex and basolateral amygdala, and elevated c-Fos or Zif268 expression in central nucleus of the amygdala and medial paracapsular intercalated cell mass, relative to C57BL/6J. Collectively, these data demonstrate a deficit in fear extinction in 129S1 associated with a failure to properly engage corticolimbic extinction circuitry. This common inbred strain provides a novel model for studying impaired fear extinction in anxiety disorders.

  4. Impaired fear extinction learning and cortico-amygdala circuit abnormalities in a common genetic mouse strain

    PubMed Central

    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 C57BL/6J for one-trial and multi-trial fear conditioning, nociception, and extinction of conditioned taste aversion (CTA) and an appetitive instrumental response. 129S1 were tested for sensitivity to the extinction-facilitating effects of extended training, as well as D-cycloserine and yohimbine treatment. To elucidate the neural basis of impaired 129S1 fear extinction, c-Fos and Zif268 expression was mapped following extinction recall. Results showed that impaired fear extinction in 129S1 was unrelated to altered fear conditioning or nociception, and was dissociable from intact appetitive extinction. Yohimbine treatment facilitated extinction in 129S1, but neither extended extinction training nor D-cycloserine treatment improved 129S1 extinction. Following extinction recall, 129S1 showed reduced c-Fos and Zif268 expression in the infralimbic cortex and basolateral amygdala, and elevated c-Fos or Zif268 expression in central nucleus of the amygdala and medial paracapsular intercalated cell mass, relative to C57BL/6J. Collectively, these data demonstrate a deficit in fear extinction in 129S1 associated with a failure to properly engage corticolimbic extinction circuitry. This common inbred strain provides a novel model for studying impaired fear extinction in anxiety disorders. PMID:18685032

  5. Repeated extinction and reversal learning of an approach response supports an arousal-mediated learning model

    PubMed Central

    Podlesnik, Christopher A.; Sanabria, Federico

    2016-01-01

    We assessed the effects of repeated extinction and reversals of two conditional stimuli (CS+/CS−) on an appetitive conditioned approach response in rats. Three results were observed that could not be accounted for by a simple linear operator model such as the one proposed by Rescorla and Wagner (1972): (1) responding to a CS− declined faster when a CS+ was simultaneously extinguished; (2) reacquisition of pre-extinction performance recovered rapidly within one session; and (3) reversal of CS+/CS− contingencies resulted in a more rapid recovery to the current CS− (former CS+) than the current CS+, accompanied by a slower acquisition of performance to the current CS+. An arousal parameter that mediates learning was introduced to a linear operator model to account for these effects. The arousal-mediated learning model adequately fit the data and predicted data from a second experiment with different rats in which only repeated reversals of CS+/CS− were assessed. According to this arousal-mediated learning model, learning is accelerated by US-elicited arousal and it slows down in the absence of US. Because arousal varies faster than conditioning, the model accounts for the decline in responding during extinction mainly through a reduction in arousal, not a change in learning. By preserving learning during extinction, the model is able to account for relapse effects like rapid reacquisition, renewal, and reinstatement. PMID:21172410

  6. Paid Educational Leave and Self-Directed Learning: Implications for Legislation on the Learning Leave Scheme in South Korea

    ERIC Educational Resources Information Center

    Oh, Jeong Rok; Park, Cho Hyun; Jo, Sung Jun

    2016-01-01

    Purpose: The purposes of this study are to explore paid educational leave (PEL), self-directed learning (SDL) and the relationship between them; and to identify the implications for legislation on the learning leave scheme in South Korea. Design/Methodology/Approach: The research method of the study is a literature review. Articles were identified…

  7. Paid Educational Leave and Self-Directed Learning: Implications for Legislation on the Learning Leave Scheme in South Korea

    ERIC Educational Resources Information Center

    Oh, Jeong Rok; Park, Cho Hyun; Jo, Sung Jun

    2016-01-01

    Purpose: The purposes of this study are to explore paid educational leave (PEL), self-directed learning (SDL) and the relationship between them; and to identify the implications for legislation on the learning leave scheme in South Korea. Design/Methodology/Approach: The research method of the study is a literature review. Articles were identified…

  8. Cannabinoid modulation of prefrontal-limbic activation during fear extinction learning and recall in humans.

    PubMed

    Rabinak, Christine A; Angstadt, Mike; Lyons, Maryssa; Mori, Shoko; Milad, Mohammed R; Liberzon, Israel; Phan, K Luan

    2014-09-01

    Pre-extinction administration of Δ9-tetrahydrocannibinol (THC) facilitates recall of extinction in healthy humans, and evidence from animal studies suggest that this likely occurs via enhancement of the cannabinoid system within the ventromedial prefrontal cortex (vmPFC) and hippocampus (HIPP), brain structures critical to fear extinction. However, the effect of cannabinoids on the underlying neural circuitry of extinction memory recall in humans has not been demonstrated. We conducted a functional magnetic resonance imaging (fMRI) study using a randomized, double-blind, placebo-controlled, between-subjects design (N=14/group) coupled with a standard Pavlovian fear extinction paradigm and an acute pharmacological challenge with oral dronabinol (synthetic THC) in healthy adult volunteers. We examined the effects of THC on vmPFC and HIPP activation when tested for recall of extinction learning 24 h after extinction learning. Compared to subjects who received placebo, participants who received THC showed increased vmPFC and HIPP activation to a previously extinguished conditioned stimulus (CS+E) during extinction memory recall. This study provides the first evidence that pre-extinction administration of THC modulates prefrontal-limbic circuits during fear extinction in humans and prompts future investigation to test if cannabinoid agonists can rescue or correct the impaired behavioral and neural function during extinction recall in patients with PTSD. Ultimately, the cannabinoid system may serve as a promising target for innovative intervention strategies (e.g. pharmacological enhancement of exposure-based therapy) in PTSD and other fear learning-related disorders.

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

    PubMed

    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. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. mGluR5 positive allosteric modulation enhances extinction learning following cocaine self-administration.

    PubMed

    Cleva, Richard M; Hicks, Megan P; Gass, Justin T; Wischerath, Kelly C; Plasters, Elizabeth T; Widholm, John J; Olive, M Foster

    2011-02-01

    Extinction of classically and instrumentally conditioned behaviors, such as conditioned fear and drug-seeking behavior, is a process of active learning, and recent studies indicate that potentiation of glutamatergic transmission facilitates extinction learning. In this study, the authors investigated the effects of the Type-5 metabotropic glutamate receptors (mGluR5) positive allosteric modulator 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide (CDPPB) on the extinction of cocaine-seeking behavior in rats with a history of intravenous cocaine self-administration. To assess its effects on acquisition and consolidation of extinction learning, CDPPB (60 mg/kg) or vehicle was administered either 20 min prior to, or immediately following, each of 10 extinction sessions, respectively. When administered prior to each extinction session, CDPPB produced a significant reduction in the number of active lever presses on all 10 days of extinction training as compared to vehicle-treated animals. When administered following each extinction session, a significant reduction in the number of active lever presses was observed on the 2nd through 10th day of extinction. Both treatment regimens also reduced the number of extinction-training sessions required to meet extinction criteria. Pre- or postextinction-training administration of CDPPB did not alter responding on the inactive lever and had no effects on open field locomotor activity. These data indicate that positive allosteric modulation of mGluR5 receptors facilitates the acquisition and consolidation of extinction learning following cocaine self-administration and may provide a novel pharmacological approach to enhancing extinction learning when combined with cue exposure therapy for the treatment of cocaine addiction. (PsycINFO Database Record (c) 2011 APA, all rights reserved).

  11. Tricyclic antidepressants: effects on extinction and fear learning.

    PubMed

    Ellison, G; Handel, J; Rogers, R; Weiss, J

    1975-01-01

    Rats trained to run an alley for a food reward were extinguished following injections of different antidepressants. When retested several days later, the animals extinguished following pretreatment with the NE reuptake blocker protriptyline showed faster running speeds than did the other groups. Other rats given electrical shocks following pretreatment with protriptyline avoided the compartment in which they had been shocked less than did animals shocked following pretreatment with other antidepressants. This implies an interferance with some aspect of the learning or consolidation process which is correlated with the degree of NE reuptake blockage. It is hypothesized that NE terminals are deactivated following frustrative nonreward or punishment by the conversion and reuptake of the released NE to an altered extinction molecule.

  12. Activation of the infralimbic cortex in a fear context enhances extinction learning

    PubMed Central

    Thompson, Brittany M.; Baratta, Michael V.; Biedenkapp, Joseph C.; Rudy, Jerry W.; Watkins, Linda R.; Maier, Steven F.

    2010-01-01

    Activation of the infralimbic region (IL) of the medial prefrontal cortex (mPFC) reduces conditioned fear in a variety of situations, and the IL is thought to play an important role in the extinction of conditioned fear. Here we report a series of experiments using contextual fear conditioning in which the IL is activated with the GABAa antagonist picrotoxin (Ptx) during a single extinction session in the fear context. We investigate the impact of this manipulation on subsequent extinction sessions in which Ptx is no longer present. First, we demonstrate that a single treatment with intra-IL Ptx administered in a conditioned fear context greatly accelerates the rate of extinction on the following days. Importantly, IL-Ptx also enhances extinction to a different fear context than the one in which IL-Ptx was administered. Thus, IL-Ptx primes extinction learning regardless of the fear context in which the IL was initially activated. Second, activation of the IL must occur in conjunction with a fear context in order to enhance extinction; the extinction enhancing effect is not observable if IL-Ptx is administered in a neutral context. Finally, this extinction enhancing effect is specific to the IL for it does not occur if Ptx is injected into the prelimbic region (PL) of the mPFC. The results indicate a novel persisting control of fear induced by activation of the IL and suggest that IL activation induces changes in extinction-related circuitry that prime extinction learning. PMID:21041382

  13. Pre-trauma individual differences in extinction learning predict posttraumatic stress.

    PubMed

    Lommen, Miriam J J; Engelhard, Iris M; Sijbrandij, Marit; van den Hout, Marcel A; Hermans, Dirk

    2013-02-01

    In the aftermath of a traumatic event, many people suffer from psychological distress, but only a minority develops posttraumatic stress disorder (PTSD). Pre-trauma individual differences in fear conditioning, most notably reduced extinction learning, have been proposed as playing an important role in the etiology of PTSD. However, prospective data are lacking. In this study, we prospectively tested whether reduced extinction was a predictor for later posttraumatic stress. Dutch soldiers (N = 249) were administered a conditioning task before their four-month deployment to Afghanistan to asses individual differences in extinction learning. After returning home, posttraumatic stress was measured. Results showed that reduced extinction learning before deployment predicted subsequent PTSD symptom severity, over and beyond degree of pre-deployment stress symptoms, neuroticism, and exposure to stressors on deployment. The findings suggest that reduced extinction learning may play a role in the development of PTSD.

  14. A Role of Protein Degradation in Memory Consolidation after Initial Learning and Extinction Learning in the Honeybee ("Apis mellifera")

    ERIC Educational Resources Information Center

    Felsenberg, Johannes; Dombrowski, Vincent; Eisenhardt, Dorothea

    2012-01-01

    Protein degradation is known to affect memory formation after extinction learning. We demonstrate here that an inhibitor of protein degradation, MG132, interferes with memory formation after extinction learning in a classical appetitive conditioning paradigm. In addition, we find an enhancement of memory formation when the same inhibitor is…

  15. A Role of Protein Degradation in Memory Consolidation after Initial Learning and Extinction Learning in the Honeybee ("Apis mellifera")

    ERIC Educational Resources Information Center

    Felsenberg, Johannes; Dombrowski, Vincent; Eisenhardt, Dorothea

    2012-01-01

    Protein degradation is known to affect memory formation after extinction learning. We demonstrate here that an inhibitor of protein degradation, MG132, interferes with memory formation after extinction learning in a classical appetitive conditioning paradigm. In addition, we find an enhancement of memory formation when the same inhibitor is…

  16. Cortisol modifies extinction learning of recently acquired fear in men.

    PubMed

    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.

  17. Cortisol modifies extinction learning of recently acquired fear in men

    PubMed Central

    Hermann, Andrea; Stark, Rudolf; Wolf, Oliver Tobias

    2014-01-01

    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

  18. Extinction and Renewal of Pavlovian Modulation in Human Sequential Feature Positive Discrimination Learning

    ERIC Educational Resources Information Center

    Baeyens, Frank; Vansteenwegen, Debora; Beckers, Tom; Hermans, Dirk; Kerkhof, Ineke; De Ceulaer, Annick

    2005-01-01

    Using a conditioned suppression task, we investigated extinction and renewal of Pavlovian modulation in human sequential Feature Positive (FP) discrimination learning. In Experiment 1, in context a participants were first trained on two FP discriminations, X[right arrow]A+/A- and Y[right arrow]B+/B-. Extinction treatment was administered in the…

  19. Context Switch Effects on Acquisition and Extinction in Human Predictive Learning

    ERIC Educational Resources Information Center

    Rosas, Juan M.; Callejas-Aguilera, Jose E.

    2006-01-01

    Four experiments tested context switch effects on acquisition and extinction in human predictive learning. A context switch impaired probability judgments about a cue-outcome relationship when the cue was trained in a context in which a different cue underwent extinction. The context switch also impaired judgments about a cue trained in a context…

  20. Extinction as New Learning versus Unlearning: Considerations from a Computer Simulation of the Cerebellum

    ERIC Educational Resources Information Center

    Mauk, Michael D.; Ohyama, Tatsuya

    2004-01-01

    Like many forms of Pavlovian conditioning, eyelid conditioning displays robust extinction. We used a computer simulation of the cerebellum as a tool to consider the widely accepted view that extinction involves new, inhibitory learning rather than unlearning of acquisition. Previously, this simulation suggested basic mechanistic features of…

  1. Extinction and Renewal of Pavlovian Modulation in Human Sequential Feature Positive Discrimination Learning

    ERIC Educational Resources Information Center

    Baeyens, Frank; Vansteenwegen, Debora; Beckers, Tom; Hermans, Dirk; Kerkhof, Ineke; De Ceulaer, Annick

    2005-01-01

    Using a conditioned suppression task, we investigated extinction and renewal of Pavlovian modulation in human sequential Feature Positive (FP) discrimination learning. In Experiment 1, in context a participants were first trained on two FP discriminations, X[right arrow]A+/A- and Y[right arrow]B+/B-. Extinction treatment was administered in the…

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

    ERIC Educational Resources Information Center

    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…

  3. Cued Reacquisition Trials during Extinction Weaken Contextual Renewal in Human Predictive Learning

    ERIC Educational Resources Information Center

    Effting, Marieke; Vervliet, Bram; Beckers, Tom; Kindt, Merel

    2013-01-01

    Extinction is generally more context specific than acquisition, as illustrated by the renewal effect. While most strategies to counteract renewal focus on decreasing the context specificity of extinction, the present work aimed at increasing the context specificity of acquisition learning. Two experiments examined whether presenting cued…

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

    ERIC Educational Resources Information Center

    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…

  5. Cued Reacquisition Trials during Extinction Weaken Contextual Renewal in Human Predictive Learning

    ERIC Educational Resources Information Center

    Effting, Marieke; Vervliet, Bram; Beckers, Tom; Kindt, Merel

    2013-01-01

    Extinction is generally more context specific than acquisition, as illustrated by the renewal effect. While most strategies to counteract renewal focus on decreasing the context specificity of extinction, the present work aimed at increasing the context specificity of acquisition learning. Two experiments examined whether presenting cued…

  6. Extinction-induced neuroplasticity attenuates stress-induced cocaine seeking: a state-dependent learning hypothesis.

    PubMed

    Self, David W; Choi, Kwang-Ho

    2004-09-01

    Chronic drug use weakens excitatory neocortical input to the nucleus accumbens (NAc). We previously reported that extinction training, a form of inhibitory learning that progressively reduces cocaine-seeking behaviour when reward is withheld, reverses this deficit by up-regulating GluR1 and GluR2/3 subunits of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) glutamate receptors in the NAc. The level of GluR1 up-regulation is positively associated with a reduction in cocaine seeking, suggesting that extinction-induced up-regulation in AMPA receptors in the NAc opposes motivational influences that maintain cocaine seeking. This hypothesis is supported by the finding that over-expression of GluR1 and GluR2 in the NAc facilitates extinction of cocaine self-administration. Furthermore, a single extinction training session conducted during GluR1 and GluR2 over-expression strongly and selectively attenuates the ability of an environmental stressor to trigger relapse to cocaine seeking long after GluR1 and GluR2 over-expression declines. These results could suggest that excitatory input to the NAc promotes extinction learning, but only when memory is recalled under stressful situations. Recent studies indicate that both environmental stress and the frustrative stress of withholding reward during extinction of drug self-administration induce similar neurochemical events in the NAc. These neurochemical events could impose a "state-dependency" on extinction learning such that subsequent exposure to stress acts as a cue to enhance retrieval of extinction memory. Our results suggest that extinction-induced up-regulation in NAc AMPA receptors acts reciprocally to facilitate state-dependent extinction learning, as stressful situations evoke extinction memories that exert powerful inhibitory control over drug-seeking behaviour. These results may have important therapeutic implications for behaviour-based approaches aimed at treating drug addiction.

  7. Forming competing fear learning and extinction memories in adolescence makes fear difficult to inhibit.

    PubMed

    Baker, Kathryn D; Richardson, Rick

    2015-11-01

    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. We examined neural correlates of impaired extinction retention by detection of phosphorylated mitogen-activated protein kinase immunoreactivity (pMAPK-IR) in several brain regions. Unexpectedly, adolescent rats exhibited good extinction retention if fear was acquired before adolescence. Further, fear acquired in adolescence could be successfully extinguished in adulthood but not within adolescence. Adolescent rats did not show extinction-induced increases in pMAPK-IR in the medial prefrontal cortex or the basolateral amygdala, or a pattern of reduced caudal central amygdala pMAPK-IR, as was observed in juveniles. This dampened prefrontal and basolateral amygdala MAPK activation following extinction in adolescence occurred even when there was no impairment in extinction retention. In contrast, only adolescent animals that exhibited impaired extinction retention showed elevated pMAPK-IR in the posterior paraventricular thalamus. These data suggest that neither the animal's age at the time of fear acquisition or extinction determines whether impaired extinction retention is exhibited. Rather, it appears that forming competing fear conditioning and extinction memories in adolescence renders this a vulnerable developmental period in which fear is difficult to inhibit. Furthermore, even under conditions that promote good extinction, the neural correlates of extinction in adolescence are different than those recruited in animals of other ages. © 2015 Baker and Richardson; Published by Cold Spring Harbor Laboratory Press.

  8. Forming competing fear learning and extinction memories in adolescence makes fear difficult to inhibit

    PubMed Central

    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. We examined neural correlates of impaired extinction retention by detection of phosphorylated mitogen-activated protein kinase immunoreactivity (pMAPK-IR) in several brain regions. Unexpectedly, adolescent rats exhibited good extinction retention if fear was acquired before adolescence. Further, fear acquired in adolescence could be successfully extinguished in adulthood but not within adolescence. Adolescent rats did not show extinction-induced increases in pMAPK-IR in the medial prefrontal cortex or the basolateral amygdala, or a pattern of reduced caudal central amygdala pMAPK-IR, as was observed in juveniles. This dampened prefrontal and basolateral amygdala MAPK activation following extinction in adolescence occurred even when there was no impairment in extinction retention. In contrast, only adolescent animals that exhibited impaired extinction retention showed elevated pMAPK-IR in the posterior paraventricular thalamus. These data suggest that neither the animal's age at the time of fear acquisition or extinction determines whether impaired extinction retention is exhibited. Rather, it appears that forming competing fear conditioning and extinction memories in adolescence renders this a vulnerable developmental period in which fear is difficult to inhibit. Furthermore, even under conditions that promote good extinction, the neural correlates of extinction in adolescence are different than those recruited in animals of other ages. PMID:26472643

  9. Nothing is safe: Intolerance of uncertainty is associated with compromised fear extinction learning.

    PubMed

    Morriss, Jayne; Christakou, Anastasia; van Reekum, Carien M

    2016-12-01

    Extinction-resistant fear is considered to be a central feature of pathological anxiety. Here we sought to determine if individual differences in Intolerance of Uncertainty (IU), a potential risk factor for anxiety disorders, underlies compromised fear extinction. We tested this hypothesis by recording electrodermal activity in 38 healthy participants during fear acquisition and extinction. We assessed the temporality of fear extinction, by examining early and late extinction learning. During early extinction, low IU was associated with larger skin conductance responses to learned threat vs. safety cues, whereas high IU was associated with skin conductance responding to both threat and safety cues, but no cue discrimination. During late extinction, low IU showed no difference in skin conductance between learned threat and safety cues, whilst high IU predicted continued fear expression to learned threat, indexed by larger skin conductance to threat vs. safety cues. These findings suggest a critical role of uncertainty-based mechanisms in the maintenance of learned fear. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  10. Reconciling reinforcement learning models with behavioral extinction and renewal: implications for addiction, relapse, and problem gambling.

    PubMed

    Redish, A David; Jensen, Steve; Johnson, Adam; Kurth-Nelson, Zeb

    2007-07-01

    Because learned associations are quickly renewed following extinction, the extinction process must include processes other than unlearning. However, reinforcement learning models, such as the temporal difference reinforcement learning (TDRL) model, treat extinction as an unlearning of associated value and are thus unable to capture renewal. TDRL models are based on the hypothesis that dopamine carries a reward prediction error signal; these models predict reward by driving that reward error to zero. The authors construct a TDRL model that can accommodate extinction and renewal through two simple processes: (a) a TDRL process that learns the value of situation-action pairs and (b) a situation recognition process that categorizes the observed cues into situations. This model has implications for dysfunctional states, including relapse after addiction and problem gambling.

  11. Post-Learning Sleep Transiently Boosts Context Specific Operant Extinction Memory

    PubMed Central

    Borquez, Margarita; Contreras, María P.; Vivaldi, Ennio; Born, Jan; Inostroza, Marion

    2017-01-01

    Operant extinction is learning to supress a previously rewarded behavior. It is known to be strongly associated with the specific context in which it was acquired, which limits the therapeutic use of operant extinction in behavioral treatments, e.g., of addiction. We examined whether sleep influences contextual memory of operant extinction over time, using two different recall tests (Recent and Remote). Rats were trained in an operant conditioning task (lever press) in context A, then underwent extinction training in context B, followed by a 3-h retention period that contained either spontaneous morning sleep, morning sleep deprivation, or spontaneous evening wakefulness. A recall test was performed either immediately after the 3-h experimental retention period (Recent recall) or after 48 h (Remote), in the extinction context B and in a novel context C. The two main findings were: (i) at the Recent recall test, sleep in comparison with sleep deprivation and spontaneous wakefulness enhanced extinction memory but, only in the extinction context B; (ii) at the Remote recall, extinction performance after sleep was enhanced in both contexts B and C to an extent comparable to levels at Recent recall in context B. Interestingly, extinction performance at Remote recall was also improved in the sleep deprivation groups in both contexts, with no difference to performance in the sleep group. Our results suggest that 3 h of post-learning sleep transiently facilitate the context specificity of operant extinction at a Recent recall. However, the improvement and contextual generalization of operant extinction memory observed in the long-term, i.e., after 48 h, does not require immediate post-learning sleep. PMID:28491027

  12. Cannabinoid modulation of prefrontal-limbic activation during fear extinction learning and recall in humans

    PubMed Central

    Rabinak, Christine A.; Angstadt, Mike; Lyons, Maryssa; Mori, Shoko; Milad, Mohammed R.; Liberzon, Israel; Phan, K. Luan

    2013-01-01

    Pre-extinction administration of ∆9-tetrahydrocannibinol (THC) facilitates recall of extinction in healthy humans, and evidence from animal studies suggest that this likely involves via enhancement of the cannabinoid system within the ventromedial prefrontal cortex (vmPFC) and hippocampus (HIPP), brain structures critical to fear extinction. However, the effect of cannabinoids on the underlying neural circuitry of extinction memory recall in humans has not been demonstrated. We conducted a functional magnetic resonance imaging (fMRI) study using a randomized, double-blind, placebo-controlled, between-subjects design (N=14/group) coupled with a standard Pavlovian fear extinction paradigm and an acute pharmacological challenge with oral dronabinol (synthetic THC) in healthy adult volunteers. We examined the effects of THC on vmPFC and HIPP activation when tested for recall of extinction learning 24 hours after extinction learning. Compared to subjects who received placebo, participants who received THC showed increased vmPFC and HIPP activation to a previously extinguished conditioned stimulus (CS+E) during extinction memory recall. This study provides the first evidence that pre-extinction administration of THC modulates prefrontal-limbic circuits during fear extinction in humans and prompts future investigation to test if cannabinoid agonists can rescue or correct the impaired behavioral and neural function during extinction recall in patients with PTSD. Ultimately, the cannabinoid system may serve as a promising target for innovative intervention strategies (e.g. pharmacological enhancement of exposure-based therapy) in PTSD and other fear learning-related disorders. PMID:24055595

  13. Male bumblebees perform learning flights on leaving a flower but not when leaving their nest.

    PubMed

    Robert, Théo; Frasnelli, Elisa; Collett, Thomas S; Hempel de Ibarra, Natalie

    2017-03-01

    Female bees and wasps demonstrate, through their performance of elaborate learning flights, when and where they memorise features of a significant site. An important feature of these flights is that the insects look back to fixate the site that they are leaving. Females, which forage for nectar and pollen and return with it to the nest, execute learning flights on their initial departure from both their nest and newly discovered flowers. To our knowledge, these flights have so far only been studied in females. Here, we describe and analyse putative learning flights observed in male bumblebees Bombus terrestris L. Once male bumblebees are mature, they leave their nest for good and fend for themselves. We show that, unlike female foragers, males always fly directly away from their nest, without looking back, in keeping with their indifference to their natal nest. In contrast, after males have drunk from artificial flowers, their flights on first leaving the flowers resemble the learning flights of females, particularly in their fixation of the flowers. These differences in the occurrence of female and male learning flights seem to match the diverse needs of the two sexes to learn about disparate, ecologically relevant places in their surroundings. © 2017. Published by The Company of Biologists Ltd.

  14. Insect-damaged fossil leaves record food web response to ancient climate change and extinction.

    PubMed

    Wilf, P

    2008-01-01

    Plants and herbivorous insects have dominated terrestrial ecosystems for over 300 million years. Uniquely in the fossil record, foliage with well-preserved insect damage offers abundant and diverse information both about producers and about ecological and sometimes taxonomic groups of consumers. These data are ideally suited to investigate food web response to environmental perturbations, and they represent an invaluable deep-time complement to neoecological studies of global change. Correlations between feeding diversity and temperature, between herbivory and leaf traits that are modulated by climate, and between insect diversity and plant diversity can all be investigated in deep time. To illustrate, I emphasize recent work on the time interval from the latest Cretaceous through the middle Eocene (67-47 million years ago (Ma)), including two significant events that affected life: the end-Cretaceous mass extinction (65.5 Ma) and its ensuing recovery; and globally warming temperatures across the Paleocene-Eocene boundary (55.8 Ma). Climatic effects predicted from neoecology generally hold true in these deep-time settings. Rising temperature is associated with increased herbivory in multiple studies, a result with major predictive importance for current global warming. Diverse floras are usually associated with diverse insect damage; however, recovery from the end-Cretaceous extinction reveals uncorrelated plant and insect diversity as food webs rebuilt chaotically from a drastically simplified state. Calibration studies from living forests are needed to improve interpretation of the fossil data.

  15. Extinction learning is slower, weaker and less context specific after alcohol.

    PubMed

    Bisby, James A; King, John A; Sulpizio, Valentina; Degeilh, Fanny; Valerie Curran, H; Burgess, Neil

    2015-11-01

    Alcohol is frequently involved in psychological trauma and often used by individuals to reduce fear and anxiety. We examined the effects of alcohol on fear acquisition and extinction within a virtual environment. Healthy volunteers were administered alcohol (0.4g/kg) or placebo and underwent acquisition and extinction from different viewpoints of a virtual courtyard, in which the conditioned stimulus, paired with a mild electric shock, was centrally located. Participants returned the following day to test fear recall from both viewpoints of the courtyard. Skin conductance responses were recorded as an index of conditioned fear. Successful fear acquisition under alcohol contrasted with impaired extinction learning evidenced by persistent conditioned responses (Experiment 1). Participants' impairments in extinction under alcohol correlated with impairments in remembering object-locations in the courtyard seen from one viewpoint when tested from the other viewpoint. Alcohol-induced extinction impairments were overcome by increasing the number of extinction trials (Experiment 2). However, a test of fear recall the next day showed persistent fear in the alcohol group across both viewpoints. Thus, alcohol impaired extinction rather than acquisition of fear, suggesting that extinction is more dependent than acquisition on alcohol-sensitive representations of spatial context. Overall, extinction learning under alcohol was slower, weaker and less context-specific, resulting in persistent fear at test that generalized to the extinction viewpoint. The selective effect on extinction suggests an effect of alcohol on prefrontal involvement, while the reduced context-specificity implicates the hippocampus. These findings have important implications for the use of alcohol by individuals with clinical anxiety disorders.

  16. Inhibiting DNA methylation alters olfactory extinction but not acquisition learning in Apis cerana and Apis mellifera.

    PubMed

    Gong, Zhiwen; Wang, Chao; Nieh, James C; Tan, Ken

    2016-07-01

    DNA methylation plays a key role in invertebrate acquisition and extinction memory. Honey bees have excellent olfactory learning, but the role of DNA methylation in memory formation has, to date, only been studied in Apis mellifera. We inhibited DNA methylation by inhibiting DNA methyltransferase (DNMT) with zebularine (zeb) and studied the resulting effects upon olfactory acquisition and extinction memory in two honey bee species, Apis cerana and A. mellifera. We used the proboscis extension reflex (PER) assay to measure memory. We provide the first demonstration that DNA methylation is also important in the olfactory extinction learning of A. cerana. DNMT did not reduce acquisition learning in either species. However, zeb bidirectionally and differentially altered extinction learning in both species. In particular, zeb provided 1h before acquisition learning improved extinction memory retention in A. mellifera, but reduced extinction memory retention in A. cerana. The reasons for these differences are unclear, but provide a basis for future studies to explore species-specific differences in the effects of methylation on memory formation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Vagus Nerve Stimulation as a Tool to Induce Plasticity in Pathways Relevant for Extinction Learning.

    PubMed

    Childs, Jessica E; Alvarez-Dieppa, Amanda C; McIntyre, Christa K; Kroener, Sven

    2015-08-21

    Extinction describes the process of attenuating behavioral responses to neutral stimuli when they no longer provide the reinforcement that has been maintaining the behavior. There is close correspondence between fear and human anxiety, and therefore studies of extinction learning might provide insight into the biological nature of anxiety-related disorders such as post-traumatic stress disorder, and they might help to develop strategies to treat them. Preclinical research aims to aid extinction learning and to induce targeted plasticity in extinction circuits to consolidate the newly formed memory. Vagus nerve stimulation (VNS) is a powerful approach that provides tight temporal and circuit-specific release of neurotransmitters, resulting in modulation of neuronal networks engaged in an ongoing task. VNS enhances memory consolidation in both rats and humans, and pairing VNS with exposure to conditioned cues enhances the consolidation of extinction learning in rats. Here, we provide a detailed protocol for the preparation of custom-made parts and the surgical procedures required for VNS in rats. Using this protocol we show how VNS can facilitate the extinction of conditioned fear responses in an auditory fear conditioning task. In addition, we provide evidence that VNS modulates synaptic plasticity in the pathway between the infralimbic (IL) medial prefrontal cortex and the basolateral complex of the amygdala (BLA), which is involved in the expression and modulation of extinction memory.

  18. Vagus Nerve Stimulation as a Tool to Induce Plasticity in Pathways Relevant for Extinction Learning

    PubMed Central

    Childs, Jessica E.; Alvarez-Dieppa, Amanda C.; McIntyre, Christa K.; Kroener, Sven

    2015-01-01

    Extinction describes the process of attenuating behavioral responses to neutral stimuli when they no longer provide the reinforcement that has been maintaining the behavior. There is close correspondence between fear and human anxiety, and therefore studies of extinction learning might provide insight into the biological nature of anxiety-related disorders such as post-traumatic stress disorder, and they might help to develop strategies to treat them. Preclinical research aims to aid extinction learning and to induce targeted plasticity in extinction circuits to consolidate the newly formed memory. Vagus nerve stimulation (VNS) is a powerful approach that provides tight temporal and circuit-specific release of neurotransmitters, resulting in modulation of neuronal networks engaged in an ongoing task. VNS enhances memory consolidation in both rats and humans, and pairing VNS with exposure to conditioned cues enhances the consolidation of extinction learning in rats. Here, we provide a detailed protocol for the preparation of custom-made parts and the surgical procedures required for VNS in rats. Using this protocol we show how VNS can facilitate the extinction of conditioned fear responses in an auditory fear conditioning task. In addition, we provide evidence that VNS modulates synaptic plasticity in the pathway between the infralimbic (IL) medial prefrontal cortex and the basolateral complex of the amygdala (BLA), which is involved in the expression and modulation of extinction memory. PMID:26325100

  19. Sleep Disruption, Safety Learning, and Fear Extinction in Humans: Implications for Posttraumatic Stress Disorder.

    PubMed

    Straus, Laura D; Drummond, Sean P A; Risbrough, Victoria B; Norman, Sonya B

    2017-09-24

    Fear learning is critical in the development and maintenance of posttraumatic stress disorder (PTSD) symptoms, and safety learning and extinction are necessary for recovery. Studies in animal models suggest that sleep disruption, and REM sleep fragmentation in particular, interfere with safety learning and extinction processes, and recently, studies are extending these findings to humans. A discussion of the human literature is presented here, which largely consists of experimental studies in healthy human control subjects. A theoretical model for the relationship between fear learning, sleep disruption, and impaired safety learning and extinction is proposed, which provides an explanatory framework for sleep disruption and its relationship to PTSD. Overall, findings suggest that sleep disruption plays a role in the development and maintenance of PTSD symptoms, and thus presents an important modifiable target in PTSD treatment.

  20. Extinction learning as a moderator of d-cycloserine efficacy for enhancing exposure therapy in posttraumatic stress disorder.

    PubMed

    de Kleine, Rianne A; Smits, Jasper A J; Hendriks, Gert-Jan; Becker, Eni S; van Minnen, Agnes

    2015-08-01

    Augmentation of exposure therapy with d-cycloserine (DCS) has proven efficacious across anxiety disorders, although results in PTSD have been mixed. Work in animals and anxiety-disordered patients suggest that the potentiating effects of DCS are dependent on the level of extinction learning during extinction training and exposure treatment, respectively. The aim of the current study was to replicate and extend previous work by examining the association between the degree of extinction learning and DCS efficacy in our randomized clinical trial on DCS (50 mg) versus placebo enhancement of exposure therapy in a chronic mixed-trauma PTSD sample (N=67; de Kleine, Hendriks, Kusters, Broekman, & van Minnen, 2012). The decline in subjective units of distress ratings collected during and across the exposure sessions were evaluated as indices of extinction learning. First, we examined whether extinction learning during an exposure session moderated DCS effects on self-reported PTSD symptoms at the next session. Second, we examined whether averaged extinction learning over the course of treatment interacted with group assignment to predict change over time and post treatment outcome. We did not find evidence that DCS effects were moderated by the degree of extinction learning, although, extinction learning was related to outcome regardless of group assignment. In PTSD, not one extinction-learning index has been consistently linked to DCS enhanced exposure treatment outcome. More (experimental) work needs to been done to unravel the complex interplay between extinction learning and DCS enhancement, especially in PTSD patients.

  1. Rethinking Extinction

    PubMed Central

    Dunsmoor, Joseph E.; Niv, Yael; Daw, Nathaniel; Phelps, Elizabeth A.

    2015-01-01

    Extinction serves as the leading theoretical framework and experimental model to describe how learned behaviors diminish through absence of anticipated reinforcement. In the past decade, extinction has moved beyond the realm of associative learning theory and behavioral experimentation in animals and has become a topic of considerable interest in the neuroscience of learning, memory, and emotion. Here, we review research and theories of extinction, both as a learning process and as a behavioral technique, and consider whether traditional understandings warrant a re-examination. We discuss the neurobiology, cognitive factors, and major computational theories, and revisit the predominant view that extinction results in new learning that interferes with expression of the original memory. Additionally, we reconsider the limitations of extinction as a technique to prevent the relapse of maladaptive behavior, and discuss novel approaches, informed by contemporary theoretical advances, that augment traditional extinction methods to target and potentially alter maladaptive memories. PMID:26447572

  2. Rethinking Extinction.

    PubMed

    Dunsmoor, Joseph E; Niv, Yael; Daw, Nathaniel; Phelps, Elizabeth A

    2015-10-07

    Extinction serves as the leading theoretical framework and experimental model to describe how learned behaviors diminish through absence of anticipated reinforcement. In the past decade, extinction has moved beyond the realm of associative learning theory and behavioral experimentation in animals and has become a topic of considerable interest in the neuroscience of learning, memory, and emotion. Here, we review research and theories of extinction, both as a learning process and as a behavioral technique, and consider whether traditional understandings warrant a re-examination. We discuss the neurobiology, cognitive factors, and major computational theories, and revisit the predominant view that extinction results in new learning that interferes with expression of the original memory. Additionally, we reconsider the limitations of extinction as a technique to prevent the relapse of maladaptive behavior and discuss novel approaches, informed by contemporary theoretical advances, that augment traditional extinction methods to target and potentially alter maladaptive memories.

  3. Enhancing Effects of NMDA-Receptor Blockade on Extinction Learning and Related Brain Activation Are Modulated by BMI

    PubMed Central

    Golisch, Anne; Heba, Stefanie; Glaubitz, Benjamin; Tegenthoff, Martin; Lissek, Silke

    2017-01-01

    A distributed network including prefrontal and hippocampal regions is involved in context-related extinction learning as well as in renewal. Renewal describes the recovery of an extinguished response if the context of extinction differs from the context of recall. Animal studies have demonstrated that prefrontal, but not hippocampal N-methyl-D-aspartate receptor (NMDAR) antagonism disrupted extinction learning and processing of task context. However, human studies of NMDAR in extinction learning are lacking, while NMDAR antagonism yielded contradictory results in other learning tasks. This fMRI study investigated the role of NMDAR for human behavioral and brain activation correlates of extinction and renewal. Healthy volunteers received a single dose of the NMDAR antagonist memantine prior to extinction of previously acquired stimulus-outcome associations presented in either identical or novel contexts. We observed better, and partly faster, extinction learning in participants receiving the NMDAR antagonist compared to placebo. However, memantine did not affect renewal. In both extinction and recall, the memantine group showed a deactivation in extinction-related brain regions, particularly in the prefrontal cortex, while hippocampal activity was increased. This higher hippocampal activation was in turn associated with the participants' body mass index (BMI) and extinction errors. Our results demonstrate potentially dose-related enhancing effects of memantine and highlight involvement of hippocampal NMDAR in context-related extinction learning. PMID:28326025

  4. Extinction learning deficit in a rodent model of attention-deficit hyperactivity disorder

    PubMed Central

    2012-01-01

    Background Deficient operant extinction has been hypothesized to be constitutive of ADHD dysfunction. In order to elucidate the behavioral mechanisms underlying this deficit, the performance of an animal model of ADHD, the spontaneously hypertensive rat (SHR), was compared against the performance of a control strain, the Wistar-Kyoto rat (WKY) during extinction. Method Following extensive training of lever pressing under variable interval schedules of food reinforcement (reported previously), SHR and WKY rats were exposed to two sessions of extinction training. Extinction data was analyzed using the Dynamic Bi-Exponential Refractory Model (DBERM) of operant performance. DBERM assumes that operant responses are organized in bouts separated by pauses; during extinction, bouts may decline across multiple dimensions, including frequency and length. DBERM parameters were estimated using hierarchical Bayesian modeling. Results SHR responded more than WKY during the first extinction session. DBERM parameter estimates revealed that, at the onset of extinction, SHR produced more response bouts than WKY. Over the course of extinction, response bouts progressively shortened for WKY but not for SHR. Conclusions Based on prior findings on the sensitivity of DBERM parameters to motivational and schedule manipulations, present data suggests that (1) more frequent response bouts in SHR are likely related to greater incentive motivation, and (2) the persistent length of bouts in SHR are likely related to a slower updating of the response-outcome association. Overall, these findings suggest specific motivational and learning deficits that may explain ADHD-related impairments in operant performance. PMID:23237608

  5. Looking beyond Fear and Extinction Learning: Considering Novel Treatment Targets for Anxiety

    PubMed Central

    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 durability of extinction-based treatments will be addressed. Moreover, adolescence may be a key developmental stage when threat-related perturbations emerge; therefore, targeting interventions during adolescence when these nascent processes are more malleable may alter the trajectory of anxiety disorders. PMID:25705579

  6. Pharmacological enhancement of drug cue extinction learning: translational challenges

    PubMed Central

    Kantak, K.M.; Nic Dhonnchadha, B.Á.

    2010-01-01

    Augmentation of cue exposure (extinction) therapy with cognitive-enhancing pharmacotherapy may constitute a rational strategy for the clinical management of drug relapse. While certain success has been reported for this form of therapy in anxiety disorders, in this article we highlight several obstacles that may undermine the efficacy of exposure therapy for substance use disorders. We also review translational studies that have evaluated the facilitative effects of the cognitive enhancer D-cycloserine on extinction targeting drug-related cues. Finally, important considerations for the design and implementation of future studies evaluating exposure therapy combined with pharmacotherapy for substance use disorders are discussed. PMID:21272016

  7. Sensory cortical population dynamics uniquely track behavior across learning and extinction.

    PubMed

    Moran, Anan; Katz, Donald B

    2014-01-22

    Neural responses in many cortical regions encode information relevant to behavior: information that necessarily changes as that behavior changes with learning. Although such responses are reasonably theorized to be related to behavior causation, the true nature of that relationship cannot be clarified by simple learning studies, which show primarily that responses change with experience. Neural activity that truly tracks behavior (as opposed to simply changing with experience) will not only change with learning but also change back when that learning is extinguished. Here, we directly probed for this pattern, recording the activity of ensembles of gustatory cortical single neurons as rats that normally consumed sucrose avidly were trained first to reject it (i.e., conditioned taste aversion learning) and then to enjoy it again (i.e., extinction), all within 49 h. Both learning and extinction altered cortical responses, consistent with the suggestion (based on indirect evidence) that extinction is a novel form of learning. But despite the fact that, as expected, postextinction single-neuron responses did not resemble "naive responses," ensemble response dynamics changed with learning and reverted with extinction: both the speed of stimulus processing and the relationships among ensemble responses to the different stimuli tracked behavioral relevance. These data suggest that population coding is linked to behavior with a fidelity that single-neuron coding is not.

  8. Differential Effects of Controllable Stress Exposure on Subsequent Extinction Learning in Adult Rats.

    PubMed

    Hadad-Ophir, Osnat; Brande-Eilat, Noa; Richter-Levin, Gal

    2015-01-01

    Deficits in fear extinction are thought to be related to various anxiety disorders. While failure to extinguish conditioned fear may result in pathological anxiety levels, the ability to quickly and efficiently attenuate learned fear through extinction processes can be extremely beneficial for the individual. One of the factors that may affect the efficiency of the extinction process is prior experience of stressful situations. In the current study, we examined whether exposure to controllable stress, which is suggested to induce stress resilience, can affect subsequent fear extinction. Here, following prolonged two-way shuttle (TWS) avoidance training and a validation of acquired stress controllability, adult rats underwent either cued or contextual fear-conditioning (FC), followed by an extinction session. We further evaluated long lasting alterations of GABAergic targets in the medial pre-frontal cortex (mPFC), as these were implicated in FC and extinction and stress controllability. In cued, but not in contextual fear extinction, within-session extinction was enhanced following controllable stress compared to a control group. Interestingly, impaired extinction recall was detected in both extinction types following the stress procedure. Additionally, stress controllability-dependent alterations in GABAergic markers expression in infralimbic (IL), but not prelimbic (PL) cortex, were detected. These alterations are proposed to be related to the within-session effect, but not the recall impairment. The results emphasize the contribution of prior experience on coping with subsequent stressful experiences. Moreover, the results emphasize that exposure to controllable stress does not generally facilitate future stress coping as previously claimed, but its effects are dependent on specific features of the events taking place.

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

    PubMed Central

    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

  10. Differential Effects of Controllable Stress Exposure on Subsequent Extinction Learning in Adult Rats

    PubMed Central

    Hadad-Ophir, Osnat; Brande-Eilat, Noa; Richter-Levin, Gal

    2016-01-01

    Deficits in fear extinction are thought to be related to various anxiety disorders. While failure to extinguish conditioned fear may result in pathological anxiety levels, the ability to quickly and efficiently attenuate learned fear through extinction processes can be extremely beneficial for the individual. One of the factors that may affect the efficiency of the extinction process is prior experience of stressful situations. In the current study, we examined whether exposure to controllable stress, which is suggested to induce stress resilience, can affect subsequent fear extinction. Here, following prolonged two-way shuttle (TWS) avoidance training and a validation of acquired stress controllability, adult rats underwent either cued or contextual fear-conditioning (FC), followed by an extinction session. We further evaluated long lasting alterations of GABAergic targets in the medial pre-frontal cortex (mPFC), as these were implicated in FC and extinction and stress controllability. In cued, but not in contextual fear extinction, within-session extinction was enhanced following controllable stress compared to a control group. Interestingly, impaired extinction recall was detected in both extinction types following the stress procedure. Additionally, stress controllability-dependent alterations in GABAergic markers expression in infralimbic (IL), but not prelimbic (PL) cortex, were detected. These alterations are proposed to be related to the within-session effect, but not the recall impairment. The results emphasize the contribution of prior experience on coping with subsequent stressful experiences. Moreover, the results emphasize that exposure to controllable stress does not generally facilitate future stress coping as previously claimed, but its effects are dependent on specific features of the events taking place. PMID:26793083

  11. The Plasticity of Extinction: Contribution of the Prefrontal Cortex in Treating Addiction through Inhibitory Learning

    PubMed Central

    Gass, J. T.; Chandler, L. J.

    2013-01-01

    Theories of drug addiction that incorporate various concepts from the fields of learning and memory have led to the idea that classical and operant conditioning principles underlie the compulsiveness of addictive behaviors. Relapse often results from exposure to drug-associated cues, and the ability to extinguish these conditioned behaviors through inhibitory learning could serve as a potential therapeutic approach for those who suffer from addiction. This review will examine the evidence that extinction learning alters neuronal plasticity in specific brain regions and pathways. In particular, subregions of the prefrontal cortex (PFC) and their projections to other brain regions have been shown to differentially modulate drug-seeking and extinction behavior. Additionally, there is a growing body of research demonstrating that manipulation of neuronal plasticity can alter extinction learning. Therefore, the ability to alter plasticity within areas of the PFC through pharmacological manipulation could facilitate the acquisition of extinction and provide a novel intervention to aid in the extinction of drug-related memories. PMID:23750137

  12. Behavioral and neurobiological mechanisms of extinction in Pavlovian and instrumental learning.

    PubMed

    Todd, Travis P; Vurbic, Drina; Bouton, Mark E

    2014-02-01

    This article reviews research on the behavioral and neural mechanisms of extinction as it is represented in both Pavlovian and instrumental learning. In Pavlovian extinction, repeated presentation of a signal without its reinforcer weakens behavior evoked by the signal; in instrumental extinction, repeated occurrence of a voluntary action without its reinforcer weakens the strength of the action. In either case, contemporary research at both the behavioral and neural levels of analysis has been guided by a set of extinction principles that were first generated by research conducted at the behavioral level. The review discusses these principles and illustrates how they have informed the study of both Pavlovian and instrumental extinction. It shows that behavioral and neurobiological research efforts have been tightly linked and that their results are readily integrated. Pavlovian and instrumental extinction are also controlled by compatible behavioral and neural processes. Since many behavioral effects observed in extinction can be multiply determined, we suggest that the current close connection between behavioral-level and neural-level analyses will need to continue.

  13. Extrasynaptic GABAA receptors in mediodorsal thalamic nucleus modulate fear extinction learning

    PubMed Central

    2014-01-01

    Background The gamma-amino-butyric acid (GABA) system is a critical mediator of fear extinction process. GABA can induce “phasic” or “tonic” inhibition in neurons through synaptic or extrasynaptic GABAA receptors, respectively. However, role of the thalamic “tonic GABA inhibition” in cognition has not been explored. We addressed this issue in extinction of conditioned fear in mice. Results Here, we show that GABAA receptors in the mediodorsal thalamic nucleus (MD) modulate fear extinction. Microinjection of gabazine, a GABAA receptor antagonist, into the MD decreased freezing behavior in response to the conditioned stimulus and thus facilitated fear extinction. Interestingly, microinjection of THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol), a preferential agonist for the δ-subunit of extrasynaptic GABAA receptors, into the MD attenuated fear extinction. In the opposite direction, an MD-specific knock-out of the extrasynaptic GABAA receptors facilitated fear extinction. Conclusions Our results suggest that “tonic GABA inhibition” mediated by extrasynaptic GABAA receptors in MD neurons, suppresses fear extinction learning. These results raise a possibility that pharmacological control of tonic mode of GABAA receptor activation may be a target for treatment of anxiety disorders like post-traumatic stress disorder. PMID:24886120

  14. Behavioral and Neurobiological Mechanisms of Extinction in Pavlovian and Instrumental Learning

    PubMed Central

    Todd, Travis P.; Vurbic, Drina; Bouton, Mark E.

    2013-01-01

    This article reviews research on the behavioral and neural mechanisms of extinction as it is represented in both Pavlovian and instrumental learning. In Pavlovian extinction, repeated presentation of a signal without its reinforcer weakens behavior evoked by the signal; in instrumental extinction, repeated occurrence of a voluntary action without its reinforcer weakens the strength of the action. In either case, contemporary research at both the behavioral and neural levels of analysis has been guided by a set of extinction principles that were first generated by research conducted at the behavioral level. The review discusses these principles and illustrates how they have informed the study of both Pavlovian and instrumental extinction. It shows that behavioral and neurobiological research efforts have been tightly linked and that their results are readily integrated. Pavlovian and instrumental extinction are also controlled by compatible behavioral and neural processes. Since many behavioral effects observed in extinction can be multiply determined, we suggest that the current close connection between behavioral-level and neural-level analyses will need to continue. PMID:23999219

  15. Involvement of Dopamine D1/D5 and D2 Receptors in Context-Dependent Extinction Learning and Memory Reinstatement

    PubMed Central

    André, Marion Agnès Emma; Manahan-Vaughan, Denise

    2016-01-01

    Dopamine contributes to the regulation of higher order information processing and executive control. It is important for memory consolidation processes, and for the adaptation of learned responses based on experience. In line with this, under aversive learning conditions, application of dopamine receptor antagonists prior to extinction result in enhanced memory reinstatement. Here, we investigated the contribution of the dopaminergic system to extinction and memory reinstatement (renewal) of an appetitive spatial learning task in rodents. Rats were trained for 3 days in a T-maze (context “A”) to associate a goal arm with a food reward, despite low reward probability (acquisition phase). On day 4, extinction learning (unrewarded) occurred, that was reinforced by a context change (“B”). On day 5, re-exposure to the (unrewarded) “A” context took place (renewal of context “A”, followed by extinction of context “A”). In control animals, significant extinction occurred on day 4, that was followed by an initial memory reinstatement (renewal) on day 5, that was, in turn, succeeded by extinction of renewal. Intracerebral treatment with a D1/D5-receptor antagonist prior to the extinction trials, elicited a potent enhancement of extinction in context “B”. By contrast, a D1/D5-agonist impaired renewal in context “A”. Extinction in the “A” context on day 5 was unaffected by the D1/D5-ligands. Treatment with a D2-receptor antagonist prior to extinction had no overall effect on extinction in context “B” or renewal in context “A”, although extinction of the renewal effect was impaired on day 5, compared to controls. Taken together, these data suggest that dopamine acting on the D1/D5-receptor modulates both acquisition and consolidation of context-dependent extinction. By contrast, the D2-receptor may contribute to context-independent aspects of this kind of extinction learning. PMID:26834599

  16. D-cycloserine Deters Reacquisition of Cocaine Self-Administration by Augmenting Extinction Learning

    PubMed Central

    Nic Dhonnchadha, Bríd Á; Szalay, Jonathan J; Achat-Mendes, Cindy; Platt, Donna M; Otto, Michael W; Spealman, Roger D; Kantak, Kathleen M

    2010-01-01

    Augmentation of cue exposure (extinction) therapy with cognitive-enhancing pharmacotherapy may offer an effective strategy to combat cocaine relapse. To investigate this possibility at the preclinical level, rats and squirrel monkeys were trained to self-administer cocaine paired with a brief visual cue. Lever pressing was subsequently extinguished by withholding cocaine injections while maintaining response-contingent presentations of the cue. The glycine partial agonist D-cycloserine (DCS; 15 and 30 mg/kg in rats, 3 and 10 mg/kg in monkeys) was evaluated for its effects on the rate of extinction and subsequent reacquisition of cocaine self-administration. Compared with vehicle, pretreatment with 30 mg/kg DCS 0.5 h before extinction training reduced the number of responses and latency to reach the extinction criterion in rats, but neither dose of DCS altered these measures in monkeys. In both species, pretreatment with the higher dose of DCS before extinction training significantly attenuated reacquisition of cocaine self-administration compared with either extinction training in the absence of DCS or DCS in the absence of explicit extinction. Furthermore, treatment with 30 mg/kg DCS accompanied by brief handling (a stress induction) immediately after but not 6 h after extinction training attenuated reacquisition of cocaine self-administration in rats. No adverse effects of 10 mg/kg DCS were evident in quantitative observational studies in monkeys. The results suggest that DCS augmented consolidation of extinction learning to deter reacquisition of cocaine self-administration in rats and monkeys. The results suggest that DCS combined with exposure therapy may constitute a rational strategy for the clinical management of cocaine relapse. PMID:19741593

  17. The disruptive effects of the CB1 receptor antagonist rimonabant on extinction learning in mice are task-specific.

    PubMed

    Niyuhire, Floride; Varvel, Stephen A; Thorpe, Andrew J; Stokes, Rene J; Wiley, Jenny L; Lichtman, Aron H

    2007-04-01

    Disruption of CB(1) receptor signaling through the use of CB(1) (-/-) mice or the CB(1) receptor antagonist rimonabant (SR141716) has been demonstrated to impair extinction of learned responses in conditioned fear and Morris water maze tasks. In contrast, CB(1) (-/-) mice exhibited normal extinction rates in an appetitively motivated operant conditioning task. The purpose of this study was to test whether rimonabant would differentially disrupt extinction learning between fear-motivated and food-motivated tasks. Separate groups of C57BL/6J mice were trained in two aversively motivated tasks, conditioned freezing and passive avoidance, and an appetitively motivated operant conditioning task at a fixed ratio (FR-5) schedule of food reinforcement. After acquisition, the respective reinforcers in each task were withheld, and an intraperitoneal injection of vehicle or rimonabant was given 30 min before each extinction session. Rimonabant (3 mg/kg) treatment significantly disrupted extinction in both the conditioned freezing and passive avoidance tasks but failed to affect extinction rates in the operant conditioning task, whether using daily or weekly extinction sessions. Interestingly, rimonabant (3 mg/kg) prevented the significant increases in lever pressing (i.e., extinction burst) that occurred during the first extinction session of the operant conditioning task. These results support the hypothesis that the CB(1) receptor plays a vital role in the extinction of aversive memories but is not essential for extinction of learned responses in appetitively motivated tasks.

  18. Neural correlates of two different types of extinction learning in the amygdala central nucleus

    PubMed Central

    Iordanova, Mihaela D.; Deroche, Mickael L. D.; Esber, Guillem R.; Schoenbaum, Geoffrey

    2016-01-01

    Extinction is a fundamental form of memory updating in which one learns to stop expecting an event that no longer occurs. This learning ensues when one experiences a change in environmental contingencies, that is, when an expected outcome fails to occur (simple extinction), or when a novel inflated expectation of a double outcome (overexpectation) is in conflict with the real outcome, and is a process that has been linked to amygdala function. Here, we show that in rats, the same neuronal population in the amygdala central nucleus updates reward expectancies and behaviour in both types of extinction, and neural changes in one paradigm are reflected in the other. This work may have implications for the management of addiction and anxiety disorders that require treatments based on the outcome omission, and disorders such as obesity that could use overexpectation, but not omission strategies. PMID:27531638

  19. Brain morphology correlates of interindividual differences in conditioned fear acquisition and extinction learning.

    PubMed

    Winkelmann, Tobias; Grimm, Oliver; Pohlack, Sebastian T; Nees, Frauke; Cacciaglia, Raffaele; Dinu-Biringer, Ramona; Steiger, Frauke; Wicking, Manon; Ruttorf, Michaela; Schad, Lothar R; Flor, Herta

    2016-05-01

    The neural circuits underlying fear learning have been intensively investigated in pavlovian fear conditioning paradigms across species. These studies established a predominant role for the amygdala in fear acquisition, while the ventromedial prefrontal cortex (vmPFC) has been shown to be important in the extinction of conditioned fear. However, studies on morphological correlates of fear learning could not consistently confirm an association with these structures. The objective of the present study was to investigate if interindividual differences in morphology of the amygdala and the vmPFC are related to differences in fear acquisition and extinction learning in humans. We performed structural magnetic resonance imaging in 68 healthy participants who underwent a differential cued fear conditioning paradigm. Volumes of subcortical structures as well as cortical thickness were computed by the semi-automated segmentation software Freesurfer. Stronger acquisition of fear as indexed by skin conductance responses was associated with larger right amygdala volume, while the degree of extinction learning was positively correlated with cortical thickness of the right vmPFC. Both findings could be conceptually replicated in an independent sample of 53 subjects. The data complement our understanding of the role of human brain morphology in the mechanisms of the acquisition and extinction of conditioned fear.

  20. Hyperresponsiveness of the Neural Fear Network During Fear Conditioning and Extinction Learning in Male Cocaine Users.

    PubMed

    Kaag, Anne Marije; Levar, Nina; Woutersen, Karlijn; Homberg, Judith; van den Brink, Wim; Reneman, Liesbeth; van Wingen, Guido

    2016-10-01

    The authors investigated whether cocaine use disorder is associated with abnormalities in the neural underpinnings of aversive conditioning and extinction learning, as these processes may play an important role in the development and persistence of drug abuse. Forty male regular cocaine users and 51 male control subjects underwent a fear conditioning and extinction protocol during functional MRI. Skin conductance response was measured throughout the experiment as an index of conditioned responses. Cocaine users showed hyperresponsiveness of the amygdala and insula during fear conditioning, as well as hyporesponsiveness of the dorsomedial prefrontal cortex during extinction learning. In cocaine users, but not in control subjects, skin conductance responses were positively correlated with responsiveness of the insula, amygdala, and dorsomedial prefrontal cortex during fear conditioning but negatively correlated with responsiveness of the ventromedial prefrontal cortex during extinction learning. Increased sensitivity to aversive conditioned cues in cocaine users might be a risk factor for stress-relief craving in cocaine use disorder. These results support the postulated role of altered aversive conditioning in cocaine use disorder and may be an important step in understanding the role of aversive learning in the pathology of cocaine use disorder.

  1. Learning and the persistence of appetite: extinction and the motivation to eat and overeat.

    PubMed

    Bouton, Mark E

    2011-04-18

    The modern world is saturated with highly palatable and highly available food, providing many opportunities to associate food with environmental cues and actions (through Pavlovian and operant or instrumental learning, respectively). Basic learning processes can often increase the tendency to approach and consume food, whereas extinction, in which Pavlovian and operant behaviors decline when the reinforcer is withheld, weakens but does not erase those tendencies. Contemporary research suggests that extinction involves an inhibitory form of new learning that appears fragile because it is highly dependent on the context for expression. These ideas are supported by the phenomena of renewal, spontaneous recovery, resurgence, reinstatement, and rapid reacquisition in appetitive learning, which together may help explain why overeating may be difficult to suppress permanently, and why appetitive behavior may seem so persistent.

  2. Preventing the return of fear using reconsolidation updating and methylene blue is differentially dependent on extinction learning

    PubMed Central

    Auchter, Allison M.; Shumake, Jason; Gonzalez-Lima, Francisco; Monfils, Marie H.

    2017-01-01

    Many factors account for how well individuals extinguish conditioned fears, such as genetic variability, learning capacity and conditions under which extinction training is administered. We predicted that memory-based interventions would be more effective to reduce the reinstatement of fear in subjects genetically predisposed to display more extinction learning. We tested this hypothesis in rats genetically selected for differences in fear extinction using two strategies: (1) attenuation of fear memory using post-retrieval extinction training, and (2) pharmacological enhancement of the extinction memory after extinction training by low-dose USP methylene blue (MB). Subjects selectively bred for divergent extinction phenotypes were fear conditioned to a tone stimulus and administered either standard extinction training or retrieval + extinction. Following extinction, subjects received injections of saline or MB. Both reconsolidation updating and MB administration showed beneficial effects in preventing fear reinstatement, but differed in the groups they targeted. Reconsolidation updating showed an overall effect in reducing fear reinstatement, whereas pharmacological memory enhancement using MB was an effective strategy, but only for individuals who were responsive to extinction. PMID:28397861

  3. Therapeutic Effects of Extinction Learning as a Model of Exposure Therapy in Rats.

    PubMed

    Fucich, Elizabeth A; Paredes, Denisse; Morilak, David A

    2016-12-01

    Current treatments for stress-related psychiatric disorders, such as depression and posttraumatic stress disorder (PTSD), are inadequate. Cognitive behavioral psychotherapies, including exposure therapy, are an alternative to pharmacotherapy, but the neurobiological mechanisms are unknown. Preclinical models demonstrating therapeutic effects of behavioral interventions are required to investigate such mechanisms. Exposure therapy bears similarity to extinction learning. Thus, we investigated the therapeutic effects of extinction learning as a behavioral intervention to model exposure therapy in rats, testing its effectiveness in reversing chronic stress-induced deficits in cognitive flexibility and coping behavior that resemble dimensions of depression and PTSD. Rats were fear-conditioned by pairing a tone with footshock, and then exposed to chronic unpredictable stress (CUS) that induces deficits in cognitive set-shifting and active coping behavior. They then received an extinction learning session as a therapeutic intervention by repeated exposure to the tone with no shock. Effects on cognitive flexibility and coping behavior were assessed 24 h later on the attentional set-shifting test or shock-probe defensive burying test, respectively. Extinction reversed the CUS-induced deficits in cognitive flexibility and coping behavior, and increased phosphorylation of ribosomal protein S6 in the medial prefrontal cortex (mPFC) of stress-compromised rats, suggesting a role for activity-dependent protein synthesis in the therapeutic effect. Inhibiting protein synthesis by microinjecting anisomycin into mPFC blocked the therapeutic effect of extinction on cognitive flexibility. These results demonstrate the utility of extinction as a model by which to study mechanisms underlying exposure therapy, and suggest these mechanisms involve protein synthesis in the mPFC, the further study of which may identify novel therapeutic targets.

  4. Lesions of the lateral habenula facilitate active avoidance learning and threat extinction.

    PubMed

    Song, Mihee; Jo, Yong Sang; Lee, Yeon-Kyung; Choi, June-Seek

    2017-02-01

    The lateral habenula (LHb) is an epithalamic brain structure that provides strong projections to midbrain monoaminergic systems that are involved in motivation, emotion, and reinforcement learning. LHb neurons are known to convey information about aversive outcomes and negative prediction errors, suggesting a role in learning from aversive events. To test this idea, we examined the effects of electrolytic lesions of the LHb on signaled two-way active avoidance learning in which rats were trained to avoid an unconditioned stimulus (US) by taking a proactive shuttling response to an auditory conditioned stimulus (CS). The lesioned animals learned the avoidance response significantly faster than the control groups. In a separate experiment, we also investigated whether the LHb contributes to Pavlovian threat (fear) conditioning and extinction. Following paired presentations of the CS and the US, LHb-lesioned animals showed normal acquisition of conditioned response (CR) measured with freezing. However, extinction of the CR in the subsequent CS-only session was significantly faster. The enhanced performance in avoidance learning and in threat extinction jointly suggests that the LHb normally plays an inhibitory role in learning driven by absence of aversive outcomes.

  5. Role of the hippocampus and amygdala in the extinction of fear-motivated learning.

    PubMed

    Vianna, Monica R; Coitinho, Adriana S; Izquierdo, Ivan

    2004-01-01

    Fear-motivated learning is at the root of phobias, panic, generalized anxiety and the posttraumatic stress disorder. This makes the inhibition of fear-motivated behavior a therapeutic desideratum in these diseases. The simplest way to accomplish this is by extinction, a procedure by which a given association between a conditioned stimulus or context (CS) and a fearsome event is replaced by a new association between the CS and the lack of the fearsome stimulus. This is a new learning for the subject and, in rats, it requires gene expression and protein synthesis both in the hippocampus and the basolateral amygdala, alongside with the activation of various metabolic signaling pathways. These requirements are similar to, but not identical with those for consolidation of the original memory. In addition, some systems uninvolved in original consolidation appear to be involved in extinction, namely, the endocannabinoid system. Extinction can be enhanced by prolonging the exposure to the lack of fearsome stimulation; e.g., in rats, by increasing the time of permanence in the compartment where the animals no longer receive a footshock. Further research into the possibilities of enhancing extinction at the expense of the original fearsome learning is desirable.

  6. Fear learning and extinction are linked to neuronal plasticity through Rin1 signaling.

    PubMed

    Bliss, Joanne M; Gray, Erin E; Dhaka, Ajay; O'Dell, Thomas J; Colicelli, John

    2010-03-01

    The amygdala is known to have a crucial role in both the acquisition and extinction of conditioned fear, but the physiological changes and biochemical mechanisms underlying these forms of learning are only partly understood. The Ras effector Rin1 activates Abl tyrosine kinases and Rab5 GTPases and is highly expressed in mature neurons of the telencephalon including the amygdala, where it inhibits the acquisition of fear memories (Rin1(-/-) mice show enhanced learning of conditioned fear). Here we report that Rin1(-/-) mice exhibit profound deficits in both latent inhibition and fear extinction, suggesting a critical role for Rin1 in gating the acquisition and persistence of cue-dependent fear conditioning. Surprisingly, we also find that depotentiation, a proposed cellular mechanism of extinction, is enhanced at lateral-basolateral (LA-BLA) amygdaloid synapses in Rin1(-/-) mice. Inhibition of a single Rin1 downstream effector pathway, the Abl tyrosine kinases, led to reduced amygdaloid depotentiation, arguing that proper coordination of Abl and Rab5 pathways is critical for Rin1-mediated effects on plasticity. While demonstrating a correlation between amygdala plasticity and fear learning, our findings argue against models proposing a direct causative relationship between amygdala depotentiation and fear extinction. Taken together, the behavior and physiology of Rin1(-/-) mice provide new insights into the regulation of memory acquisition and maintenance. In addition, Rin1(-/-) mice should prove useful as a model for pathologies marked by enhanced fear acquisition and retention, such as posttraumatic stress disorder.

  7. Students with Special Educational Needs in Secondary Education: Are They Intending to Learn or to Leave?

    ERIC Educational Resources Information Center

    Pijl, Sip Jan; Frostad, Per; Mjaavatn, Per Egil

    2014-01-01

    During their secondary school years, a considerable number of students seriously consider choosing between learning and leaving. Leaving school early means that students do not complete their education. Early school leaving is the last step in a process in which students gradually lose interest and develop the intention to leave school. This study…

  8. Enhancement of extinction learning attenuates ethanol-seeking behavior and alters plasticity in the prefrontal cortex.

    PubMed

    Gass, Justin T; Trantham-Davidson, Heather; Kassab, Amanda S; Glen, William B; Olive, M Foster; Chandler, L Judson

    2014-05-28

    Addiction is a chronic relapsing disorder in which relapse is often initiated by exposure to drug-related cues. The present study examined the effects of mGluR5 activation on extinction of ethanol-cue-maintained responding, relapse-like behavior, and neuronal plasticity. Rats were trained to self-administer ethanol and then exposed to extinction training during which they were administered either vehicle or the mGluR5 positive allosteric modulator 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl) or CDPPB. CDPPB treatment reduced active lever responding during extinction, decreased the total number of extinction sessions required to meet criteria, and attenuated cue-induced reinstatement of ethanol seeking. CDPPB facilitation of extinction was blocked by the local infusion of the mGluR5 antagonist 3-((2-methyl-4-thiazolyl)ethynyl) pyridine into the infralimbic (IfL) cortex, but had no effect when infused into the prelimbic (PrL) cortex. Analysis of dendritic spines revealed alterations in structural plasticity, whereas electrophysiological recordings demonstrated differential alterations in glutamatergic neurotransmission in the PrL and IfL cortex. Extinction was associated with increased amplitude of evoked synaptic PrL and IfL NMDA currents but reduced amplitude of PrL AMPA currents. Treatment with CDPPB prevented the extinction-induced enhancement of NMDA currents in PrL without affecting NMDA currents in the IfL. Whereas CDPPB treatment did not alter the amplitude of PrL or IfL AMPA currents, it did promote the expression of IfL calcium-permeable GluR2-lacking receptors in both abstinence- and extinction-trained rats, but had no effect in ethanol-naive rats. These results confirm changes in the PrL and IfL cortex in glutamatergic neurotransmission during extinction learning and demonstrate that manipulation of mGluR5 facilitates extinction of ethanol cues in association with neuronal plasticity.

  9. Enhancement of Extinction Learning Attenuates Ethanol-Seeking Behavior and Alters Plasticity in the Prefrontal Cortex

    PubMed Central

    Trantham-Davidson, Heather; Kassab, Amanda S.; Glen, William B.; Olive, M. Foster; Chandler, L. Judson

    2014-01-01

    Addiction is a chronic relapsing disorder in which relapse is often initiated by exposure to drug-related cues. The present study examined the effects of mGluR5 activation on extinction of ethanol-cue-maintained responding, relapse-like behavior, and neuronal plasticity. Rats were trained to self-administer ethanol and then exposed to extinction training during which they were administered either vehicle or the mGluR5 positive allosteric modulator 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl) or CDPPB. CDPPB treatment reduced active lever responding during extinction, decreased the total number of extinction sessions required to meet criteria, and attenuated cue-induced reinstatement of ethanol seeking. CDPPB facilitation of extinction was blocked by the local infusion of the mGluR5 antagonist 3-((2-methyl-4-thiazolyl)ethynyl) pyridine into the infralimbic (IfL) cortex, but had no effect when infused into the prelimbic (PrL) cortex. Analysis of dendritic spines revealed alterations in structural plasticity, whereas electrophysiological recordings demonstrated differential alterations in glutamatergic neurotransmission in the PrL and IfL cortex. Extinction was associated with increased amplitude of evoked synaptic PrL and IfL NMDA currents but reduced amplitude of PrL AMPA currents. Treatment with CDPPB prevented the extinction-induced enhancement of NMDA currents in PrL without affecting NMDA currents in the IfL. Whereas CDPPB treatment did not alter the amplitude of PrL or IfL AMPA currents, it did promote the expression of IfL calcium-permeable GluR2-lacking receptors in both abstinence- and extinction-trained rats, but had no effect in ethanol-naive rats. These results confirm changes in the PrL and IfL cortex in glutamatergic neurotransmission during extinction learning and demonstrate that manipulation of mGluR5 facilitates extinction of ethanol cues in association with neuronal plasticity. PMID:24872560

  10. Extinction learning, which consists of the inhibition of retrieval, can be learned without retrieval.

    PubMed

    de Carvalho Myskiw, Jociane; Furini, Cristiane Regina Guerino; Schmidt, Bianca; Ferreira, Flávia; Izquierdo, Ivan

    2015-01-13

    In the present study we test the hypothesis that extinction is not a consequence of retrieval in unreinforced conditioned stimulus (CS) presentation but the mere perception of the CS in the absence of a conditioned response. Animals with cannulae implanted in the CA1 region of hippocampus were subjected to extinction of contextual fear conditioning. Muscimol infused intra-CA1 before an extinction training session of contextual fear conditioning (CFC) blocks retrieval but not consolidation of extinction measured 24 h later. Additionally, this inhibition of retrieval does not affect early persistence of extinction when tested 7 d later or its spontaneous recovery after 2 wk. Furthermore, both anisomycin, an inhibitor of ribosomal protein synthesis, and rapamycin, an inhibitor of extraribosomal protein synthesis, given into the CA1, impair extinction of CFC regardless of whether its retrieval was blocked by muscimol. Therefore, retrieval performance in the first unreinforced session is not necessary for the installation, maintenance, or spontaneous recovery of extinction of CFC.

  11. Sleep promotes consolidation and generalization of extinction learning in simulated exposure therapy for spider fear.

    PubMed

    Pace-Schott, Edward F; Verga, Patrick W; Bennett, Tobias S; Spencer, Rebecca M C

    2012-08-01

    Simulated exposure therapy for spider phobia served as a clinically naturalistic model to study effects of sleep on extinction. Spider-fearing, young adult women (N = 66), instrumented for skin conductance response (SCR), heart rate acceleration (HRA) and corrugator electromyography (EMG), viewed 14 identical 1-min videos of a behaving spider before a 12-hr delay containing a normal night's Sleep (N = 20) or continuous daytime Wake (N = 23), or a 2-hr delay of continuous wake in the Morning (N = 11) or Evening (N = 12). Following the delay, all groups viewed this same video 6 times followed by six 1-min videos of a novel spider. After each video, participants rated disgust, fearfulness and unpleasantness. In all 4 groups, all measures except corrugator EMG diminished across Session 1 (extinction learning) and, excepting SCR to a sudden noise, increased from the old to novel spider in Session 2. In Wake only, summed subjective ratings and SCR to the old spider significantly increased across the delay (extinction loss) and were greater for the novel vs. the old spider when it was equally novel at the beginning of Session 1 (sensitization). In Sleep only, SCR to a sudden noise decreased across the inter-session delay (extinction augmentation) and, along with HRA, was lower to the novel spider than initially to the old spider in Session 1 (extinction generalization). None of the above differentiated Morning and Evening groups suggesting that intervening sleep, rather than time-of-testing, produced differences between Sleep and Wake. Thus, sleep following exposure therapy may promote retention and generalization of extinction learning.

  12. Sleep Promotes Consolidation and Generalization of Extinction Learning in Simulated Exposure Therapy for Spider Fear

    PubMed Central

    Pace-Schott, Edward F.; Verga, Patrick; Bennet, Tobias; Spencer, Rebecca M.C.

    2012-01-01

    Simulated exposure therapy for spider phobia served as a clinically naturalistic model to study effects of sleep on extinction. Spider-fearing, young adult women (N=66), instrumented for skin conductance response (SCR), heart rate acceleration (HRA) and corrugator electromyography (EMG), viewed 14 identical 1-min videos of a behaving spider before a 12-hr delay containing a normal night’s Sleep (N=20) or continuous daytime Wake (N=23), or a 2-hr delay of continuous wake in the Morning (N=11) or Evening (N=12). Following the delay, all groups viewed this same video 6 times followed by six 1-min videos of a novel spider. After each video, participants rated disgust, fearfulness and unpleasantness. In all 4 groups, all measures except corrugator EMG diminished across Session 1 (extinction learning) and, excepting SCR to a sudden noise, increased from the old to novel spider in Session 2. In Wake only, summed subjective ratings and SCR to the old spider significantly increased across the delay (extinction loss) and were greater for the novel vs. the old spider when it was equally novel at the beginning of Session 1 (sensitization). In Sleep only, SCR to a sudden noise decreased across the inter-session delay (extinction augmentation) and, along with HRA, was lower to the novel spider than initially to the old spider in Session 1 (extinction generalization). None of the above differentiated Morning and Evening groups suggesting that intervening sleep, rather than time-of-testing, produced differences between Sleep and Wake. Thus, sleep following exposure therapy may promote retention and generalization of extinction learning. PMID:22578824

  13. Conditioned fear and extinction learning performance and its association with psychiatric symptoms in active duty Marines

    PubMed Central

    Acheson, D.T.; Geyer, M.A.; Baker, D.G.; Nievergelt, C.M.; Yurgil, K.; Risbrough, V.B.

    2014-01-01

    Summary Background Posttraumatic Stress Disorder (PTSD) is a major public health concern, especially given the recent wars in Iraq and Afghanistan. Nevertheless, despite a sharp increase in the incidence of psychiatric disorders in returning veterans, empirically based prevention strategies are still lacking. To develop effective prevention and treatment strategies, it is necessary to understand the underlying biological mechanisms contributing to PTSD and other trauma related symptoms. Methods The “Marine Resiliency Study II” (MRS-II; October 2011–October 2013) Neurocognition project is an investigation of neurocognitive performance in Marines about to be deployed to Afghanistan. As part of this investigation, 1195 Marines and Navy corpsmen underwent a fear conditioning and extinction paradigm and psychiatric symptom assessment prior to deployment. The current study assesses (1) the effectiveness of the fear potentiated startle paradigm in producing fear learning and extinction and (2) the association of performance in the paradigm with baseline psychiatric symptom classes (healthy: n = 923, PTSD symptoms: n = 42, anxiety symptoms: n = 37, and depression symptoms: n = 12). Results Results suggest that the task was effective in producing differential fear learning and fear extinction in this cohort. Further, distinct patterns emerged differentiating the PTSD and anxiety symptom classes from both healthy and depression classes. During fear acquisition, the PTSD symptom group was the only group to show deficient discrimination between the conditioned stimulus (CS+) and safety cue (CS−), exhibiting larger startle responses during the safety cue compared to the healthy group. During extinction learning, the PTSD symptom group showed significantly less reduction in their CS+ responding over time compared to the healthy group, as well as reduced extinction of self-reported anxiety to the CS+ by the end of the extinction session. Conversely, the anxiety symptom

  14. Value Learning and Arousal in the Extinction of Probabilistic Rewards: The Role of Dopamine in a Modified Temporal Difference Model

    PubMed Central

    Song, Minryung R.; Fellous, Jean-Marc

    2014-01-01

    Because most rewarding events are probabilistic and changing, the extinction of probabilistic rewards is important for survival. It has been proposed that the extinction of probabilistic rewards depends on arousal and the amount of learning of reward values. Midbrain dopamine neurons were suggested to play a role in both arousal and learning reward values. Despite extensive research on modeling dopaminergic activity in reward learning (e.g. temporal difference models), few studies have been done on modeling its role in arousal. Although temporal difference models capture key characteristics of dopaminergic activity during the extinction of deterministic rewards, they have been less successful at simulating the extinction of probabilistic rewards. By adding an arousal signal to a temporal difference model, we were able to simulate the extinction of probabilistic rewards and its dependence on the amount of learning. Our simulations propose that arousal allows the probability of reward to have lasting effects on the updating of reward value, which slows the extinction of low probability rewards. Using this model, we predicted that, by signaling the prediction error, dopamine determines the learned reward value that has to be extinguished during extinction and participates in regulating the size of the arousal signal that controls the learning rate. These predictions were supported by pharmacological experiments in rats. PMID:24586823

  15. Value learning and arousal in the extinction of probabilistic rewards: the role of dopamine in a modified temporal difference model.

    PubMed

    Song, Minryung R; Fellous, Jean-Marc

    2014-01-01

    Because most rewarding events are probabilistic and changing, the extinction of probabilistic rewards is important for survival. It has been proposed that the extinction of probabilistic rewards depends on arousal and the amount of learning of reward values. Midbrain dopamine neurons were suggested to play a role in both arousal and learning reward values. Despite extensive research on modeling dopaminergic activity in reward learning (e.g. temporal difference models), few studies have been done on modeling its role in arousal. Although temporal difference models capture key characteristics of dopaminergic activity during the extinction of deterministic rewards, they have been less successful at simulating the extinction of probabilistic rewards. By adding an arousal signal to a temporal difference model, we were able to simulate the extinction of probabilistic rewards and its dependence on the amount of learning. Our simulations propose that arousal allows the probability of reward to have lasting effects on the updating of reward value, which slows the extinction of low probability rewards. Using this model, we predicted that, by signaling the prediction error, dopamine determines the learned reward value that has to be extinguished during extinction and participates in regulating the size of the arousal signal that controls the learning rate. These predictions were supported by pharmacological experiments in rats.

  16. Autophosphorylation of [alpha]CaMKII is Differentially Involved in New Learning and Unlearning Mechanisms of Memory Extinction

    ERIC Educational Resources Information Center

    Kimura, Ryoichi; Silva, Alcino J.; Ohno, Masuo

    2008-01-01

    Accumulating evidence indicates the key role of [alpha]-calcium/calmodulin-dependent protein kinase II ([alpha]CaMKII) in synaptic plasticity and learning, but it remains unclear how this kinase participates in the processing of memory extinction. Here, we investigated the mechanism by which [alpha]CaMKII may mediate extinction by using…

  17. Distinct Contributions of the Basolateral Amygdala and the Medial Prefrontal Cortex to Learning and Relearning Extinction of Context Conditioned Fear

    ERIC Educational Resources Information Center

    Laurent, Vincent; Westbrook, R. Frederick

    2008-01-01

    We studied the roles of the basolateral amygdala (BLA) and the medial prefrontal cortex (mPFC) in learning and relearning to inhibit context conditioned fear (freezing) in extinction. In Experiment 1, pre-extinction BLA infusion of the NMDA receptor (NMDAr) antagonist, ifenprodil, impaired the development and retention of inhibition but…

  18. Autophosphorylation of [alpha]CaMKII is Differentially Involved in New Learning and Unlearning Mechanisms of Memory Extinction

    ERIC Educational Resources Information Center

    Kimura, Ryoichi; Silva, Alcino J.; Ohno, Masuo

    2008-01-01

    Accumulating evidence indicates the key role of [alpha]-calcium/calmodulin-dependent protein kinase II ([alpha]CaMKII) in synaptic plasticity and learning, but it remains unclear how this kinase participates in the processing of memory extinction. Here, we investigated the mechanism by which [alpha]CaMKII may mediate extinction by using…

  19. Distinct Contributions of the Basolateral Amygdala and the Medial Prefrontal Cortex to Learning and Relearning Extinction of Context Conditioned Fear

    ERIC Educational Resources Information Center

    Laurent, Vincent; Westbrook, R. Frederick

    2008-01-01

    We studied the roles of the basolateral amygdala (BLA) and the medial prefrontal cortex (mPFC) in learning and relearning to inhibit context conditioned fear (freezing) in extinction. In Experiment 1, pre-extinction BLA infusion of the NMDA receptor (NMDAr) antagonist, ifenprodil, impaired the development and retention of inhibition but…

  20. Dissociation of the Role of Infralimbic Cortex in Learning and Consolidation of Extinction of Recent and Remote Aversion Memory.

    PubMed

    Awad, Walaa; Ferreira, Guillaume; Maroun, Mouna

    2015-10-01

    Medial prefrontal circuits have been reported to undergo a major reorganization over time and gradually take a more important role for remote emotional memories such as contextual fear memory or food aversion memory. The medial prefrontal cortex, and specifically its ventral subregion, the infralimbic cortex (IL), was also reported to be critical for recent memory extinction of contextual fear conditioning and conditioned odor aversion. However, its exact role in the extinction of remotely acquired information is still not clear. Using postretrieval blockade of protein synthesis or inactivation of the IL, we showed that the IL is similarly required for extinction consolidation of recent and remote fear memory. However, in odor aversion memory, the IL was only involved in extinction consolidation of recent, but not remote, memory. In contrast, only remote retrieval of aversion memory induced c-Fos activation in the IL and preretrieval inactivation of the IL with lidocaine impaired subsequent extinction of remote but not recent memory, indicating IL is necessary for extinction learning of remote aversion memory. In contrast to the effects in odor aversion, our data show that the involvement of the IL in the consolidation of fear extinction does not depend on the memory age. More importantly, our data indicate that the IL is implicated in the extinction of fear and nonfear-based associations and suggest dissociation in the engagement of the IL in the learning and consolidation of food aversion extinction over time.

  1. Leaving

    ERIC Educational Resources Information Center

    Jones, Robyn L.

    2011-01-01

    Within this article, the author presents a personal story, "Leaving," which highlights the problematic experience of opposing established practice. The tale tells of the difficulty faced by creative agency when confronted by a constraining structural hegemony. Specifically, it draws attention to the professionalization of academic life through a…

  2. Leaving

    ERIC Educational Resources Information Center

    Jones, Robyn L.

    2011-01-01

    Within this article, the author presents a personal story, "Leaving," which highlights the problematic experience of opposing established practice. The tale tells of the difficulty faced by creative agency when confronted by a constraining structural hegemony. Specifically, it draws attention to the professionalization of academic life through a…

  3. EtOH self-administration on shuttle box avoidance learning and extinction in rats.

    PubMed

    Pallarés, M A; Nadal, R A; Hernández-Torres, M; Ferré, N A

    1997-01-01

    The effects of ethanol on the acquisition and extinction of the two-way active avoidance response were examined in adult, male Wistar rats from two treatment groups, oral self-administration of alcohol solution (10% v/v ethanol and 3% w/v glucose in distilled water) and oral self-administration of control solution (3% w/v glucose in distilled water). Alcohol or control solutions were available 1 h per day during 15 days simultaneously with food, with free water for the rest of the day. Blood was drawn in the last day of this phase to evaluate blood ethanol levels (BEL). After this period, rats were tested in a two-bottle paradigm for 1 h per day and placed in a shuttle box immediately afterwards. This phase went lasted for 10 days. Subjects were trained to avoid an electric foot shock in the first 5 days (15 trials per day). Following this, half of the subjects were tested in an "easy extinction with punishment" (EEP) and the other half in a "difficult extinction with punishment" (DEP) of the avoidance response for the last 5 days. Alcohol accelerates the avoidance responding acquisition, and no significant effects of alcohol were seen in the extinction phase. Data are discussed in terms of the specificity of the effects of alcohol on learning.

  4. Learning deficits expressed as delayed extinction of a conditioned running response following perinatal exposure to vinclozolin.

    PubMed

    André, Susan M; Markowski, Vincent P

    2006-01-01

    Vinclozolin (Vz) is one member of a group of fungicides whose metabolites are androgen receptor antagonists. These fungicides have been shown to block androgen-driven development and compromise reproductive function. The current study sought to determine if Vz also affects learning following exposure to low doses during the perinatal period. To test this, an androgen-dependent behavior was examined, the extinction of a previously reinforced running response. Pregnant Long-Evans rats were administered a daily oral dose of 0, 1.5, 3, 6 or 12 mg/kg Vz from the 14th day of gestation through postnatal day 3. After reaching adulthood, male and female offspring were trained to run through a short alleyway for food reinforcement. Acquisition of the response was not affected by Vz exposure. However, males required more trials than females for response extinction once food was no longer available in the apparatus. Males exposed to 6 or 12 mg/kg Vz failed to show any extinction by the end of the procedure, while the lowest dose of Vz appeared to facilitate extinction in both male and female offspring. These results demonstrate that endocrine disrupting antiandrogens can alter nervous system development in addition to the reproductive system.

  5. Extinction of appetitive learning is disrupted by cycloheximide and propranolol in the sand maze in rats.

    PubMed

    Cohen, Joshua; Gotthard, Gretchen Hanson

    2011-05-01

    The present study investigated whether memory for extinction in an appetitive task (the sand maze) could be attenuated by administration of cycloheximide (protein synthesis inhibitor) or propranolol (β-adrenergic receptor antagonist). Ninety-day-old male Long-Evans rats were trained to retrieve a sweet cereal reinforcer from an open container in the sand maze. One day following this non-spatial training, rats received three extinction trials in which they were placed in the maze with the reinforcer present, but unattainable. Thirty minutes prior to the first extinction trial, rats received an intraperitoneal injection of cycloheximide (1mg/kg), propranolol (25mg/kg), or vehicle (1mg/kg distilled water). Twenty-four hours later, rats were tested in the sand maze with the reinforcer again available. Results from the test trial showed that both cycloheximide and propranolol groups found the reinforcer more quickly than controls. Two weeks later, rats were trained on a spatial version of the sand maze in which they had to search for a buried reinforcer using extramaze cues. Cycloheximide and propranolol groups learned this task significantly faster than the control group, demonstrating the long-lasting effect of cycloheximide and propranolol on the blocking of memory for extinction.

  6. Extinction learning in childhood anxiety disorders, obsessive compulsive disorder and post-traumatic stress disorder: implications for treatment.

    PubMed

    McGuire, Joseph F; Orr, Scott P; Essoe, Joey K-Y; McCracken, James T; Storch, Eric A; Piacentini, John

    2016-10-01

    Threat conditioning and extinction play an important role in anxiety disorders, obsessive compulsive disorder (OCD), and post-traumatic stress disorder (PTSD). Although these conditions commonly affect children, threat conditioning and extinction have been primarily studied in adults. However, differences in phenomenology and neural architecture prohibit the generalization of adult findings to youth. A comprehensive literature search using PubMed and PsycInfo was conducted to identify studies that have used differential conditioning tasks to examine threat acquisition and extinction in youth. The information obtained from this review helps to clarify the influence of these processes on the etiology and treatment of youth with OCD, PTSD and other anxiety disorders. Thirty studies of threat conditioning and extinction were identified Expert commentary: Youth with anxiety disorders, OCD, and PTSD have largely comparable threat acquisition relative to unaffected controls, with some distinctions noted for youth with PTSD or youth who have suffered maltreatment. However, impaired extinction was consistently observed across youth with these disorders and appears to be consistent with deficiencies in inhibitory learning. Incorporating strategies to improve inhibitory learning may improve extinction learning within extinction-based treatments like cognitive behavioral therapy (CBT). Strategies to improve inhibitory learning in CBT are discussed.

  7. In vitro extinction learning in Hermissenda: involvement of conditioned inhibition molecules

    PubMed Central

    Cavallo, Joel S.; Hamilton, Brittany N.; Farley, Joseph

    2014-01-01

    Extinction of a conditioned association is typically viewed as the establishment of new learning rather than the erasure of the original memory. However, recent research in the nudibranch, Hermissenda crassicornis (H.c.) demonstrated that extinction training (using repeated light-alone presentations) given 15 min, but not 23 h, after memory acquisition reversed both the cellular correlates of learning (enhanced Type B cell excitability) and the behavioral changes (reduced phototaxis) produced by associative conditioning (pairings of light, CS, and rotation, US). Here, we investigated the putative molecular signaling pathways that underlie this extinction in H.c. by using a novel in vitro protocol combined with pharmacological manipulations. After intact H.c. received either light-rotation pairings (Paired), random presentations of light and rotation (Random), or no stimulation (Untrained), B cells from isolated CNSs were recorded from during exposure to extinction training consisting of two series of 15 consecutive light-steps (LSs). When in vitro extinction was administered shortly (2 h, but not 24 h) after paired training, B cells from Paired animals showed progressive and robust declines in spike frequency by the 30th LS, while control cells (Random and Untrained) did not. We found that several molecules implicated in H.c. conditioned inhibitory (CI) learning, protein phosphatase 1 (PP1) and arachidonic acid (AA)/12-lipoxygenase (12-LOX) metabolites, also contributed to the spike frequency decreases produced by in vitro extinction. Protein phosphatase 2B (PP2B) also appeared to play a role. Calyculin A (PP1 inhibitor), cyclosporin A (PP2B inhibitor), and baicalein (a 12-LOX inhibitor) all blocked the spike frequency declines in Paired B cells produced by 30 LSs. Conversely, injection of catalytically-active PP1 (caPP1) or PP2B (caPP2B) into Untrained B cells partially mimicked the spike frequency declines observed in Paired cells, as did bath-applied AA, and

  8. Extinction learning, which consists of the inhibition of retrieval, can be learned without retrieval

    PubMed Central

    de Carvalho Myskiw, Jociane; Furini, Cristiane Regina Guerino; Schmidt, Bianca; Ferreira, Flávia; Izquierdo, Ivan

    2015-01-01

    In the present study we test the hypothesis that extinction is not a consequence of retrieval in unreinforced conditioned stimulus (CS) presentation but the mere perception of the CS in the absence of a conditioned response. Animals with cannulae implanted in the CA1 region of hippocampus were subjected to extinction of contextual fear conditioning. Muscimol infused intra-CA1 before an extinction training session of contextual fear conditioning (CFC) blocks retrieval but not consolidation of extinction measured 24 h later. Additionally, this inhibition of retrieval does not affect early persistence of extinction when tested 7 d later or its spontaneous recovery after 2 wk. Furthermore, both anisomycin, an inhibitor of ribosomal protein synthesis, and rapamycin, an inhibitor of extraribosomal protein synthesis, given into the CA1, impair extinction of CFC regardless of whether its retrieval was blocked by muscimol. Therefore, retrieval performance in the first unreinforced session is not necessary for the installation, maintenance, or spontaneous recovery of extinction of CFC. PMID:25550507

  9. Evidence for the involvement of extinction-associated inhibitory learning in the forced swimming test.

    PubMed

    Campus, P; Colelli, V; Orsini, C; Sarra, D; Cabib, S

    2015-02-01

    The forced swimming test (FST) remains one of the most used tools for screening antidepressants in rodent models. Nonetheless, the nature of immobility, its main behavioral measure, is still a matter of debate. The present study took advantage of our recent finding that mice of the inbred DBA/2J strain require a functioning left dorsolateral striatum (DLS) to consolidate long-term memory of FST to test whether immobility is the outcome of stress-related learning. Infusion of the GABA-A agonist muscimol in the left DLS immediately after a single experience of FST prevented and infusion in the left or the right amygdala impaired recall of the acquired levels of immobility in a probe test performed 24h later. Post-training left DLS infusion of muscimol, at a dose capable of preventing retention of FST-induced immobility, did not influence 24h retention of inhibitory avoidance training or of the escape response acquired in a water T-maze. However, this same treatment prevented 24h retention of the extinction training of the consolidated escape response. These results indicate that a left DLS-centered memory system selectively mediates memory consolidation of FST and of escape extinction and support the hypothesis that immobility is the result of extinction-like inhibitory learning involving all available escape responses due to the inescapable/unavoidable nature of FST experience.

  10. [Effects of item-arrangement on serial pattern learning and extinction in rats].

    PubMed

    Taniuchi, T

    1997-10-01

    Two experiments using rats as subjects examined effects of item-arrangement on acquisition and extinction in serial learning. In Experiment 1, Group A received series of 16-0-16 and 1-0-1 food pellets in a runway, while Group D received 1-0-16 and 16-0-1 series. Both groups manifested a remote anticipation of the third item on Run 2, and current anticipation of the third item on Run 3. In extinction phase, resistance was greater in Group D than Group A. These results indicate that the first item signaled not only the second item, but also the third item. In Experiment 2, two of the four groups were trained with either of the following monotonic series: 0-16-0-8-0-4- 0-2-0-1 (Group M16) or 0-1-0-2-0-4-0-8-0-16 (Group M1), while the other two groups were given one of the following nonmonotonic series: 0-16-0-2-0-4-0-8-0-1 (Group NM16) or 0-1-0-8-0-4-0-2-0-16 (Group NM1). In extinction phase, Group M16 showed the least resistance. These results are discussed mainly on the basis of remote association view and structural complexity theory of serial learning.

  11. Connecting, learning, leaving: supporting young parents in the community.

    PubMed

    Mills, Annie; Schmied, Virginia; Taylor, Christine; Dahlen, Hannah; Schuiringa, Wies; Hudson, Margaret E

    2012-11-01

    Providing support and parenting education through home visiting is a key early intervention strategy with young parents. Less is known about what home visitors do that makes a difference. The purpose of this paper is to describe the role and experiences of professional staff working with young parents participating in a multicomponent parent support programme (home visiting and supported parenting groups) provided by a non-government organisation in a socially disadvantaged area of Sydney, Australia. This was a qualitative descriptive study. Data were collected through three focus groups conducted with the same six staff over an 18-month period. Participant descriptions of their role and experiences working with young mothers were analysed thematically. Additional data from 20 anonymised client records were analysed through content analysis. Analysis of the focus group data revealed two themes, 'Connecting' and 'Facilitating Learning'. The theme 'Connecting' reflected the development of a relationship with the young mother commencing with 'how do we engage them?', 'building trust' through to formation of a relationship described as 'they know we're not friends, they know we're workers'. The second theme, 'Facilitating Learning' was informed by the analysis of both group and client record data and comprised a number of themes around what and how mothers learnt, through to 'ending the relationship' as the mothers left the programme. The quality of a mothers' learning was dependent on the quality of the connection between herself and the staff, similarly their capacity and, or confidence to leave the programme was dependent on the relationship, 'connecting' and the learning undertaken. Role modelling through interactions with children as well as with each other was seen as the most effective way to facilitate social and parenting skill development, while formal education sessions were evaluated by the workers to be less successful than informal ones.

  12. Learning to forget: manipulating extinction and reconsolidation processes to treat addiction.

    PubMed

    Torregrossa, Mary M; Taylor, Jane R

    2013-04-01

    Finding effective long-lasting treatments for drug addiction has been an elusive goal. Consequently, researchers are beginning to investigate novel treatment strategies including manipulations of drug-associated memories. When environmental stimuli (cues) become associated with drug use, they become powerful motivators of continued drug use and relapse after abstinence. Reducing the strength of these cue-drug memories could decrease the number of factors that induce craving and relapse to aid in the treatment of addiction. Enhancing the consolidation of extinction learning and/or disrupting cue-drug memory reconsolidation are two strategies that have been proposed to reduce the strength of cues in motivating drug-seeking and drug-taking behavior. Here, we review the latest basic and clinical research elucidating the mechanisms underlying consolidation of extinction and reconsolidation of cue-drug memories in the hopes of developing pharmacological tools that exploit these signaling systems to treat addiction.

  13. Alterations in Expression and Phosphorylation of GluA1 Receptors following Cocaine-Cue Extinction Learning

    PubMed Central

    Nic Dhonnchadha, BÁ; Lin, A; Leite-Morris, KA; Kaplan, GB; Man, HY; Kantak, KM

    2012-01-01

    Brain regional analyses of total GluA1 and GluA1-pSer845 were used to delineate plasticity of the AMPA receptor in conjunction with cocaine-cue extinction learning. Rats were trained to self-administer cocaine paired with a 2-sec light cue and later underwent a single 2hr extinction session for which cocaine was withheld but response-contingent cues were presented. Control groups received yoked-saline sessions or received cocaine self-administration training without undergoing extinction training. Extinction-related increases and decreases, respectively, in total GluA1 were observed in the ventromedial prefrontal cortex (vmPFC) and basolateral amygdala (BLA). Phosphorylation of GluA1 at Ser845 was increased in the vmPFC and nucleus accumbens (NAc). Though total GluA1 did not change in NAc, there was a positive association between the number of responses during extinction training and the magnitude of total GluA1 in NAc. No significant changes were evident in the dorsal hippocampus. We conclude that the BLA and vmPFC, in particular, appear to be loci for the inhibition of learned behavior induced via extinction training, but each site may have different signaling functions for cocaine-cue extinction learning. PMID:23085477

  14. Indices of extinction-induced "depression" after operant learning using a runway vs. a cued free-reward delivery schedule.

    PubMed

    Topic, Bianca; Kröger, Inga; Vildirasova, Petya G; Huston, Joseph P

    2012-11-01

    Loss of reward is one of the etiological factors leading to affective disorders, such as major depression. We have proposed several variants of an animal model of depression based on extinction of reinforced behavior of rats. A number of behaviors emitted during extinction trials were found to be attenuated by antidepressant treatment and, thus, qualified as indices of extinction-induced "despair". These include increases in immobility in the Morris water maze and withdrawal from the former source of reward as well as biting behavior in operant chambers. Here, we assess the effects of reward omission on behaviors after learning of (a) a cued free-reward delivery in an operant chamber and (b) food-reinforced runway behavior. Sixty adult male Wistar rats were either trained to receive food reinforcement every 90 s (s) after a 5s lasting cue light (FI 90), or to traverse an alley to gain food reward. Daily drug treatment with either the selective serotonin reuptake inhibitor citalopram or the tricyclic antidepressant imipramine (each 10mg/kg) or vehicle was begun either 25 days (operant chamber) or 3 days (runway) prior to extinction. The antidepressants suppressed rearing behavior in both paradigms specifically during the extinction trials, which indicates this measure as a useful marker of depression-related behavior, possibly indicating vertical withdrawal. In the operant chamber, only marginal effects on operant learning responses during extinction were found. In the runway, the operant learned responses run time and distance to the goal, as well as total distance moved, grooming and quiescence were also influenced by the antidepressants, providing a potential set of markers for extinction-induced "depression" in the runway. Both paradigms differ substantially with respect to the anticipation of reward, behaviors that are learned and that accompany extinction. Accordingly, antidepressant treatment influenced different sets of behaviors in these two learning tasks.

  15. Prelimbic cortical BDNF is required for memory of learned fear but not extinction or innate fear

    PubMed Central

    Choi, Dennis C.; Maguschak, Kimberly A.; Ye, Keqiang; Jang, Sung-Wuk; Myers, Karyn M.; Ressler, Kerry J.

    2010-01-01

    In the medial prefrontal cortex, the prelimbic area is emerging as a major modulator of fear behavior, but the mechanisms remain unclear. Using a selective neocortical knockout mouse, virally mediated prelimbic cortical-specific gene deletion, and pharmacological rescue with a TrkB agonist, we examined the role of a primary candidate mechanism, BDNF, in conditioned fear. We found consistently robust deficits in consolidation of cued fear but no effects on acquisition, expression of unlearned fear, sensorimotor function, and spatial learning. This deficit in learned fear in the BDNF knockout mice was rescued with systemic administration of a TrkB receptor agonist, 7,8-dihydroxyflavone. These data indicate that prelimbic BDNF is critical for consolidation of learned fear memories, but it is not required for innate fear or extinction of fear. Moreover, use of site-specific, inducible BDNF deletions shows a powerful mechanism that may further our understanding of the pathophysiology of fear-related disorders. PMID:20133801

  16. [Treatment of posttraumatic stress disorder and extinction learning of traumatic memory].

    PubMed

    Asukai, Nozomu

    2013-06-01

    Posttraumatic stress disorder (PTSD) is a debilitating psychological condition that develops following exposure to a traumatic event. The characteristic symptoms of PTSD are re-experience, avoidance, psychic numbing and hyper-arousal. The biological PTSD literature has been dramatically growing over the past three decades. PTSD symptoms related to re-experiencing the traumatic event may be conceptualized within a fear conditioning framework. Recent findings suggest that PTSD is associated with a failure of extinction learning of an acquired fear response. A fear-circuit model of PTSD posits that vmPFC fails to inhibit the amygdala, which has a crucial role in fear learning. Exposure therapy currently has the largest number of randomized clinical trials demonstrating its efficacy, and is recommended with substantial clinical confidence in treatment guidelines for PTSD. The efficacy of Prolonged Exposure (PE) was also shown for Japanese PTSD patients in a randomized controlled trial (Asukai et al., 2010). The emotional processing theory that accounts for the treatment mechanism of PE may be consistent with the hypothesis of a neurobiological mechanism in PTSD. D-cycloserine (DCS), an NMDA partial agonist, has been shown to facilitate extinction learning in animals and humans. Clinically, DCS has been shown to be a promising augmentation to PE, particularly for those who need longer treatment.

  17. Zinc transporter 3 is involved in learned fear and extinction, but not in innate fear.

    PubMed

    Martel, Guillaume; Hevi, Charles; Friebely, Olivia; Baybutt, Trevor; Shumyatsky, Gleb P

    2010-11-01

    Synaptically released Zn²+ 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, highly enriched in the amygdala-associated neural circuitry, and ZnT3 KO mice lack Zn²+ in synaptic vesicles. However, earlier work reported no deficiency in fear memory in ZnT3 KO mice, which is surprising based on the effects of Zn²+ on amygdala synaptic plasticity. We therefore reexamined ZnT3 KO mice in various tasks for learned and innate fear. The mutants were deficient in a weak fear-conditioning protocol using single tone-shock pairing but showed normal memory when a stronger, five-pairing protocol was used. ZnT3 KO mice were deficient in memory when a tone was presented as complex auditory information in a discontinuous fashion. Moreover, ZnT3 KO mice showed abnormality in trace fear conditioning and in fear extinction. By contrast, ZnT3 KO mice had normal anxiety. Thus, ZnT3 is involved in associative fear memory and extinction, but not in innate fear, consistent with the role of synaptic zinc in amygdala synaptic plasticity.

  18. Learning and extinction of a passive avoidance response in mice with high levels of predisposition to catalepsy.

    PubMed

    Dubrovina, N I; Zinov'ev, D R; Zinov'eva, D V; Kulikov, A V

    2009-06-01

    This report presents results obtained from comparative analysis of learning and the dynamics of extinction of a conditioned passive avoidance response in ASC mice, which were bred for a high level of predisposition to catalepsy, and in CBA and AKR mice. The following findings were obtained: 1) impairments to the extinction of the memory of fear represent an important symptom of depression in ASC mice; 2) extinction is delayed in CBA mice; and 3) new inhibitory learning occurs quickly in AKR mice. Prolonged retention of the fear memory in ASC mice appears to be related to increased anxiety on prolonged testing without a punishment. The deficit of inhibition of the fear reaction in ASC mice allows this strain to be regarded as a genetic model of depression.

  19. Systemic or Intra-Amygdala Infusion of the Benzodiazepine, Midazolam, Impairs Learning, but Facilitates Re-Learning to Inhibit Fear Responses in Extinction

    ERIC Educational Resources Information Center

    Hart, Genevra; Harris, Justin A.; Westbrook, R. Frederick

    2010-01-01

    A series of experiments used rats to study the effect of a systemic or intra-amygdala infusion of the benzodiazepine, midazolam, on learning and re-learning to inhibit context conditioned fear (freezing) responses. Rats were subjected to two context-conditioning episodes followed by extinction under drug or vehicle, or to two cycles of context…

  20. Systemic or Intra-Amygdala Infusion of the Benzodiazepine, Midazolam, Impairs Learning, but Facilitates Re-Learning to Inhibit Fear Responses in Extinction

    ERIC Educational Resources Information Center

    Hart, Genevra; Harris, Justin A.; Westbrook, R. Frederick

    2010-01-01

    A series of experiments used rats to study the effect of a systemic or intra-amygdala infusion of the benzodiazepine, midazolam, on learning and re-learning to inhibit context conditioned fear (freezing) responses. Rats were subjected to two context-conditioning episodes followed by extinction under drug or vehicle, or to two cycles of context…

  1. Partial reinforcement effects on learning and extinction of place preferences in the water maze.

    PubMed

    Prados, José; Sansa, Joan; Artigas, Antonio A

    2008-11-01

    In two experiments, two groups of rats were trained in a navigation task according to either a continuous or a partial schedule of reinforcement. In Experiment 1, animals that were given continuous reinforcement extinguished the spatial response of approaching the goal location more readily than animals given partial reinforcement-a partial reinforcement extinction effect. In Experiment 2, after partially or continuously reinforced training, animals were trained in a new task that made use of the same reinforcer according to a continuous reinforcement schedule. Animals initially given partial reinforcement performed better in the novel task than did rats initially given continuous reinforcement. These results replicate, in the spatial domain, well-known partial reinforcement phenomena typically observed in the context of Pavlovian and instrumental conditioning, suggesting that similar principles govern spatial and associative learning. The results reported support the notion that salience modulation processes play a key role in determining partial reinforcement effects.

  2. A comparison of adult and adolescent rat behavior in operant learning, extinction, and behavioral inhibition paradigms.

    PubMed

    Andrzejewski, Matthew E; Schochet, Terri L; Feit, Elizabeth C; Harris, Rachel; McKee, Brenda L; Kelley, Ann E

    2011-02-01

    Poor self-control, lack of inhibition, and impulsivity contribute to the propensity of adolescents to engage in risky or dangerous behaviors. Brain regions (e.g., prefrontal cortex) involved in impulse-control, reward-processing, and decision-making continue to develop during adolescence, raising the possibility that an immature brain contributes to dangerous behavior during adolescence. However, very few validated animal behavioral models are available for behavioral neuroscientists to explore the relationship between brain development and behavior. To that end, a valid model must be conducted in the relatively brief window of adolescence and not use manipulations that potentially compromise development. The present experiments used three operant arrangements to assess whether adolescent rats differ from adults in measures of learning, behavioral inhibition, and impulsivity, within the aforementioned time frame without substantial food restriction. In Experiment 1, separate squads of rats were trained to lever-press and then transitioned to two types of extinction. Relative to their baselines, adolescent rats responded more during extinction than adults, suggesting that they were less sensitive to the abolishment of the reinforcement contingency. Experiment 2 demonstrated similar age-related differences during exposure to a differential reinforcement of low rates schedule, a test of behavioral inhibition. Lastly, in Experiment 3, adolescent's responding decreased more slowly than adults during exposure to a resetting delay of reinforcement schedule, suggesting impaired self-control. Results from these experiments suggest that adolescents exhibit impaired learning, behavioral inhibition and self-control, and in concert with recent reports, provide researchers with three behavioral models to more fully explore neurobiology of risk-taking behavior in adolescence. (PsycINFO Database Record (c) 2011 APA, all rights reserved).

  3. Positive Allosteric Modulation of mGluR5 Accelerates Extinction Learning but Not Relearning Following Methamphetamine Self-Administration

    PubMed Central

    Kufahl, Peter R.; Hood, Lauren E.; Nemirovsky, Natali E.; Barabas, Piroska; Halstengard, Casey; Villa, Angel; Moore, Elisabeth; Watterson, Lucas R.; Olive, M. Foster

    2012-01-01

    Recent studies have implicated glutamate neurotransmission as an important substrate for the extinction of conditioned behaviors, including responding for drug reinforcement. Positive allosteric modulation of the type-5 metabotropic glutamate receptor (mGluR5) in particular has emerged as a treatment strategy for the enhancement of extinction of drug-motivated behaviors. Here, we investigated the effects of the mGluR5 positive allosteric modulator CDPPB, a compound known for its cognitive enhancing effects in rodents, on extinction learning in rats with different histories of methamphetamine (METH) training. Rats were trained to self-administer METH under two conditions: 16 daily sessions of short access (90 min/day, ShA), or eight daily sessions of short access followed by eight sessions of long access (6 h/day, LgA). Control rats self-administered sucrose pellets in daily 30 min sessions. Next, rats were administered vehicle or 30 mg/kg CDPPB prior to seven consecutive daily extinction sessions, subjected to additional extinction sessions to re-establish a post-treatment baseline, and then tested for reinstatement of behavior in the presence of METH- or sucrose-paired cues. Rats were then subjected to a second series of extinction sessions, preceded by vehicle or 30 mg/kg CDPPB, and an additional test for cue-triggered reinstatement. CDPPB treatment resulted in a more rapid extinction of responding on the active lever, especially in the early sessions of the first extinction sequence. However, treatment effects were minimal during subsequent cue reinstatement tests and non-existent during the second series of extinction sessions. Rats with histories of ShA, LgA, and sucrose training expressed similar behavioral sensitivities to CDPPB, with LgA rats demonstrating a modestly higher treatment effect. Positive allosteric modulation of mGluR5 may therefore have some beneficial effects on efforts to facilitate extinction learning and reduce methamphetamine

  4. Towards a Learning Identity: Young People Becoming Learners after Leaving School

    ERIC Educational Resources Information Center

    Higgins, Jane

    2013-01-01

    This article explores the development of learning identities among 51 young New Zealanders who left school with few or no qualifications. Most experienced a period of time after leaving school when they were not in education, employment or training (known as NEET). At the time of this research all had moved into a learning environment of some…

  5. AX+, BX- Discrimination Learning in the Fear-Potentiated Startle Paradigm: Possible Relevance to Inhibitory Fear Learning in Extinction

    PubMed Central

    Myers, Karyn M.; Davis, Michael

    2004-01-01

    The neural mechanisms of fear suppression most commonly are studied through the use of extinction, a behavioral procedure in which a feared stimulus (i.e., one previously paired with shock) is nonreinforced repeatedly, leading to a reduction or elimination of the fear response. Although extinction is perhaps the most convenient index of fear inhibition, a great deal of behavioral work suggests that postextinction training conditioned stimuli are both excitatory and inhibitory, making it difficult to determine whether a neural manipulation affects inhibition, excitation, or some combination thereof. For this reason we sought to develop a behavioral procedure that would render a stimulus primarily inhibitory while at the same time avoiding some of the issues raised by the traditional conditioned inhibition paradigm, namely second-order conditioning, external inhibition, and configural learning. Using the fear-potentiated startle paradigm, we adapted an AX+, BX- training procedure in which stimuli A and X were presented simultaneously and paired with shock, and stimuli B and X were presented simultaneously in the absence of shock. In testing, high levels of fear-potentiated startle were seen in the presence of A and AX and much lower levels were seen in the presence of B and AB, as would be predicted if stimulus B were a conditioned inhibitor. We believe this method is a viable alternative to the traditional conditioned inhibition training procedure and will be useful for studying the neural mechanisms of fear inhibition. PMID:15254216

  6. Temporal Dynamics of Recovery from Extinction Shortly after Extinction Acquisition

    ERIC Educational Resources Information Center

    Archbold, Georgina E.; Dobbek, Nick; Nader, Karim

    2013-01-01

    Evidence suggests that extinction is new learning. Memory acquisition involves both short-term memory (STM) and long-term memory (LTM) components; however, few studies have examined early phases of extinction retention. Retention of auditory fear extinction was examined at various time points. Shortly (1-4 h) after extinction acquisition…

  7. Temporal Dynamics of Recovery from Extinction Shortly after Extinction Acquisition

    ERIC Educational Resources Information Center

    Archbold, Georgina E.; Dobbek, Nick; Nader, Karim

    2013-01-01

    Evidence suggests that extinction is new learning. Memory acquisition involves both short-term memory (STM) and long-term memory (LTM) components; however, few studies have examined early phases of extinction retention. Retention of auditory fear extinction was examined at various time points. Shortly (1-4 h) after extinction acquisition…

  8. Translation of associative learning models into extinction reminders delivered via mobile phones during cue exposure interventions for substance use.

    PubMed

    Rosenthal, M Zachary; Kutlu, Munir G

    2014-09-01

    Despite experimental findings and some treatment research supporting the use of cues as a means to induce and extinguish cravings, interventions using cue exposure have not been well integrated into contemporary substance abuse treatments. A primary problem with exposure-based interventions for addiction is that after learning not to use substances in the presence of addiction cues inside the clinic (i.e., extinction), stimuli in the naturalistic setting outside the clinic may continue to elicit craving, drug use, or other maladaptive conditioned responses. For exposure-based substance use interventions to be efficacious, new approaches are needed that can prevent relapse by directly generalizing learning from the therapeutic setting into naturalistic settings associated with a high risk for relapse. Basic research suggests that extinction reminders (ERs) can be paired with the context of learning new and more adaptive conditioned responses to substance abuse cues in exposure therapies for addiction. Using mobile phones and automated dialing and data collection software, ERs can be delivered in everyday high-risk settings to inhibit conditioned responses to substance-use-related stimuli. In this review, we describe how associative learning mechanisms (e.g., conditioned inhibition) can inform how ERs are conceptualized, learned, and implemented to prevent substance use when delivered via mobile phones. This approach, exposure with portable reminders of extinction, is introduced as an adjunctive intervention that uses brief automated ERs between clinic visits when individuals are in high-risk settings for drug use.

  9. Translation of Associative Learning Models into Extinction Reminders Delivered via Mobile Phones During Cue Exposure Interventions for Substance Use

    PubMed Central

    Rosenthal, M. Zachary; Kutlu, Munir G.

    2014-01-01

    Despite experimental findings and some treatment research supporting the use of cues as a means to induce and extinguish cravings, interventions using cue exposure have not been well integrated into contemporary substance abuse treatments. A primary problem with exposure-based interventions for addiction is that after learning not to use substances in the presence of addiction cues inside the clinic (i.e., extinction), stimuli in the naturalistic setting outside the clinic may continue to elicit craving, drug use, or other maladaptive conditioned responses. For exposure-based substance use interventions to be efficacious, new approaches are needed that can prevent relapse by directly generalizing learning from the therapeutic setting into naturalistic settings associated with a high-risk for relapse. Basic research suggests that extinction reminders (ERs) can be paired with the context of learning new and more adaptive conditioned responses to substance abuse cues in exposure therapies for addiction. Using mobile phones and automated dialing and data collection software, ERs can be delivered in everyday high-risk settings to inhibit conditioned responses to substance use-related stimuli. In this review, we describe how associative learning mechanisms (e.g., conditioned inhibition) can inform how ERs are conceptualized, learned, and implemented to prevent substance use when delivered via mobile phones. This approach, exposure with portable reminders of extinction, is introduced as an adjunctive intervention that uses brief automated ERs between clinic visits when individuals are in high-risk settings for drug use. PMID:25134055

  10. Impaired Contextual Fear Extinction Learning is Associated with Aberrant Regulation of CHD-Type Chromatin Remodeling Factors.

    PubMed

    Wille, Alexandra; Maurer, Verena; Piatti, Paolo; Whittle, Nigel; Rieder, Dietmar; Singewald, Nicolas; Lusser, Alexandra

    2015-01-01

    Successful attenuation of fearful memories is a cognitive process requiring initiation of highly coordinated transcription programs. Chromatin-modulating mechanisms such as DNA methylation and histone modifications, including acetylation, are key regulators of these processes. However, knowledge concerning the role of ATP-dependent chromatin remodeling factors (ChRFs) being required for successful fear extinction is lacking. Underscoring the potential importance of these factors that alter histone-DNA contacts within nucleosomes are recent genome-wide association studies linking several ChRFs to various human cognitive and psychiatric disorders. To better understand the role of ChRFs in the brain, and since to date little is known about ChRF expression in the brain, we performed a comprehensive survey of expression levels of 24 ATP-dependent remodelers across different brain areas, and we identified several distinct high molecular weight complexes by chromatographic methods. We next aimed to gain novel insight into the potential regulation of ChRFs in different brain regions in association with normal and impaired fear extinction learning. To this end, we established the 129S1/SvImJ (S1) laboratory mouse strain as a model for compromised contextual fear extinction learning that can be rescued by dietary zinc restriction (ZnR). Using this model along with genetically related but fear extinction-competent 129S6/SvEv (S6) mice as controls, we found that impaired fear extinction in S1 was associated with enhanced ventral hippocampal expression of CHD1 and reduced expression of CHD5 that was normalized following successful rescue of impaired fear extinction. Moreover, a select reduction in CHD3 expression was observed in the ventral hippocampus (vHC) following successful rescue of fear extinction in S1 mice. Taken together, these data provide novel insight into the regulation of specific ChRFs following an impaired cognitive process and its rescue, and they suggest that

  11. Impaired Contextual Fear Extinction Learning is Associated with Aberrant Regulation of CHD-Type Chromatin Remodeling Factors

    PubMed Central

    Wille, Alexandra; Maurer, Verena; Piatti, Paolo; Whittle, Nigel; Rieder, Dietmar; Singewald, Nicolas; Lusser, Alexandra

    2015-01-01

    Successful attenuation of fearful memories is a cognitive process requiring initiation of highly coordinated transcription programs. Chromatin-modulating mechanisms such as DNA methylation and histone modifications, including acetylation, are key regulators of these processes. However, knowledge concerning the role of ATP-dependent chromatin remodeling factors (ChRFs) being required for successful fear extinction is lacking. Underscoring the potential importance of these factors that alter histone-DNA contacts within nucleosomes are recent genome-wide association studies linking several ChRFs to various human cognitive and psychiatric disorders. To better understand the role of ChRFs in the brain, and since to date little is known about ChRF expression in the brain, we performed a comprehensive survey of expression levels of 24 ATP-dependent remodelers across different brain areas, and we identified several distinct high molecular weight complexes by chromatographic methods. We next aimed to gain novel insight into the potential regulation of ChRFs in different brain regions in association with normal and impaired fear extinction learning. To this end, we established the 129S1/SvImJ (S1) laboratory mouse strain as a model for compromised contextual fear extinction learning that can be rescued by dietary zinc restriction (ZnR). Using this model along with genetically related but fear extinction-competent 129S6/SvEv (S6) mice as controls, we found that impaired fear extinction in S1 was associated with enhanced ventral hippocampal expression of CHD1 and reduced expression of CHD5 that was normalized following successful rescue of impaired fear extinction. Moreover, a select reduction in CHD3 expression was observed in the ventral hippocampus (vHC) following successful rescue of fear extinction in S1 mice. Taken together, these data provide novel insight into the regulation of specific ChRFs following an impaired cognitive process and its rescue, and they suggest that

  12. Trauma exposure relates to heightened stress, altered amygdala morphology and deficient extinction learning: Implications for psychopathology.

    PubMed

    Cacciaglia, Raffaele; Nees, Frauke; Grimm, Oliver; Ridder, Stephanie; Pohlack, Sebastian T; Diener, Slawomira J; Liebscher, Claudia; Flor, Herta

    2017-02-01

    Stress exposure causes a structural reorganization in neurons of the amygdala. In particular, animal models have repeatedly shown that both acute and chronic stress induce neuronal hypertrophy and volumetric increase in the lateral and basolateral nuclei of amygdala. These effects are visible on the behavioral level, where stress enhances anxiety behaviors and provokes greater fear learning. We assessed stress and anxiety levels in a group of 18 healthy human trauma-exposed individuals (TR group) compared to 18 non-exposed matched controls (HC group), and related these measurements to amygdala volume. Traumas included unexpected adverse experiences such as vehicle accidents or sudden loss of a loved one. As a measure of aversive learning, we implemented a cued fear conditioning paradigm. Additionally, to provide a biological marker of chronic stress, we measured the sensitivity of the hypothalamus-pituitary-adrenal (HPA) axis using a dexamethasone suppression test. Compared to the HC, the TR group showed significantly higher levels of chronic stress, current stress and trait anxiety, as well as increased volume of the left amygdala. Specifically, we observed a focal enlargement in its lateral portion, in line with previous animal data. Compared to HC, the TR group also showed enhanced late acquisition of conditioned fear and deficient extinction learning, as well as salivary cortisol hypo-suppression to dexamethasone. Left amygdala volumes positively correlated with suppressed morning salivary cortisol. Our results indicate differences in trauma-exposed individuals which resemble those previously reported in animals exposed to stress and in patients with post-traumatic stress disorder and depression. These data provide new insights into the mechanisms through which traumatic stress might prompt vulnerability for psychopathology.

  13. Early age-dependent impairments of context-dependent extinction learning, object recognition, and object-place learning occur in rats.

    PubMed

    Wiescholleck, Valentina; Emma André, Marion Agnès; Manahan-Vaughan, Denise

    2014-03-01

    The hippocampus is vulnerable to age-dependent memory decline. Multiple forms of memory depend on adequate hippocampal function. Extinction learning comprises active inhibition of no longer relevant learned information concurrent with suppression of a previously learned reaction. It is highly dependent on context, and evidence exists that it requires hippocampal activation. In this study, we addressed whether context-based extinction as well as hippocampus-dependent tasks, such as object recognition and object-place recognition, are equally affected by moderate aging. Young (7-8 week old) and older (7-8 month old) Wistar rats were used. For the extinction study, animals learned that a particular floor context indicated that they should turn into one specific arm (e.g., left) to receive a food reward. On the day after reaching the learning criterion of 80% correct choices, the floor context was changed, no reward was given and animals were expected to extinguish the learned response. Both, young and older rats managed this first extinction trial in the new context with older rats showing a faster extinction performance. One day later, animals were returned to the T-maze with the original floor context and renewal effects were assessed. In this case, only young but not older rats showed the expected renewal effect (lower extinction ratio as compared to the day before). To assess general memory abilities, animals were tested in the standard object recognition and object-place memory tasks. Evaluations were made at 5 min, 1 h and 7 day intervals. Object recognition memory was poor at short-term and intermediate time-points in older but not young rats. Object-place memory performance was unaffected at 5 min, but impaired at 1 h in older but not young rats. Both groups were impaired at 7 days. These findings support that not only aspects of general memory, but also context-dependent extinction learning, are affected by moderate aging. This may reflect less flexibility in

  14. Interoceptive conditioning with the nicotine stimulus: extinction learning as a method for assessing stimulus similarity across doses.

    PubMed

    Polewan, Robert J; Savala, Stephanie A; Bevins, Rick A

    2013-02-01

    Interoceptive conditioning involving the nicotine stimulus likely contributes to chronic tobacco use. To better understand the nature of this interoceptive conditioning, we compared generalization during repeated extinction with generalization in a 'transfer of extinction' test using a wide range of test doses. Rats were first trained in the discriminated goal-tracking task in which nicotine (0.2 or 0.4 mg/kg), but not saline, was paired with repeated intermittent access to sucrose. Across sessions, nicotine acquired control of approach behavior directed at the location of previous sucrose deliveries. Extinction followed with eight 20-min sessions without sucrose access; extinction doses of nicotine ranged from 0.05 to 0.6 mg/kg. In rats trained with 0.4 mg/kg, the 0.1, 0.2, and 0.6 mg/kg doses evoked comparable responding across extinction sessions; substitution was only partial at 0.05 and 0.075 mg/kg (i.e. above saline controls, but less than the training dose). With the 0.2 mg/kg training dose, complete generalization was seen only at the 0.1 and 0.4 mg/kg doses. After extinction, rats were given a transfer test with their training dose. Rats trained with 0.4 mg/kg showed full transfer of extinction learning with 0.1, 0.2, and 0.6 mg/kg (i.e. responding comparable with extinction with the training dose). Partial transfer was observed at 0.075 mg/kg. With the 0.2 mg/kg nicotine dose, only 0.4 mg/kg fully generalized; 0.075, 0.1, and 0.6 mg/kg showed partial transfer. Extinction with 0.05 mg/kg dose did not show transfer to either training dose. These findings indicated that conclusions regarding stimulus similarity across nicotine doses can vary with testing protocol.

  15. Occasion setting, inhibition, and the contextual control of extinction in Pavlovian and instrumental (operant) learning.

    PubMed

    Trask, Sydney; Thrailkill, Eric A; Bouton, Mark E

    2017-04-01

    An occasion setter is a stimulus that modulates the ability of another stimulus to control behavior. A rich history of experimental investigation has identified several important properties that define occasion setters and the conditions that give rise to occasion setting. In this paper, we first consider the basic hallmarks of occasion setting in Pavlovian conditioning. We then review research that has examined the mechanisms underlying the crucial role of context in Pavlovian and instrumental extinction. In Pavlovian extinction, evidence suggests that the extinction context can function as a negative occasion setter whose role is to disambiguate the current meaning of the conditioned stimulus; the conditioning context can also function as a positive occasion setter. In operant extinction, in contrast, the extinction context may directly inhibit the response, and the conditioning context can directly excite it. We outline and discuss the key results supporting these distinctions. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Evidence of a role for multiple memory systems in behavioral extinction.

    PubMed

    Gabriele, Amanda; Packard, Mark G

    2006-05-01

    The acquisition of learned behavior involves multiple memory systems, and hippocampal system damage impairs cognitive learning while leaving stimulus-response habit learning intact. In view of evidence that extinction also involves new learning, the present experiments examined whether multiple memory systems theory may be applicable to the neural bases of extinction. Adult Long-Evans rats were trained to run in a straight-alley maze for food reward. Twenty-four hours later, rats matched for runway latencies during acquisition received extinction training. In a response extinction condition conducive to habit learning, rats performed a runway approach response to an empty food cup. In a latent extinction condition conducive to cognitive learning, rats were placed at an empty food cup without performing a runway approach response. Prior to daily extinction training, neural activity of the dorsal hippocampus was reversibly inactivated via infusion of bupivacaine (0.75%, 0.5 microl/side). Control rats receiving saline infusions displayed extinction behavior in both the response and latent training conditions. In contrast, rats receiving bupivacaine extinguished normally in the response condition, but did not display latent extinction. The findings (1) confirm that learning underlying extinction of the same overt behavior can occur with or without explicit performance of the previously acquired response, (2) indicate that extinction learning produced by response and latent training procedures can be neuroanatomically dissociated, and (3) suggest that similarly to initial task acquisition, the hippocampus may critically mediate extinction in situations requiring the use of cognitive learning, such as when performance of a previously acquired response habit is prevented.

  17. Drive decay: the cause of fast "extinction" of habits learned for brain stimulation.

    PubMed

    HOWARTH, C I; DEUTSCH, J A

    1962-07-06

    According to Deutsch's theory of intracranial self-stimulation, cessation of responding after the withdrawal of the stimulus should be a simple function of time without stimulation. To test this prediction, the lever was withdrawn from a Skinner box for varying times, then replaced and normal extinction completed. The number of extinction trials was a simple function of the time the lever was out of the box, thus confirming Deutsch's hypothesis that cessation of responding in this instance is due to a decay of a motivational excitation produced by the electrical stimulation, and not a function of the number of unreinforced trials as in normal extinction.

  18. Effects of postnatal malnutrition and senescence on learning, long-term memory, and extinction in the rat.

    PubMed

    Martínez, Yvonne; Díaz-Cintra, Sofía; León-Jacinto, Uriel; Aguilar-Vázquez, Azucena; Medina, Andrea C; Quirarte, Gina L; Prado-Alcalá, Roberto A

    2009-10-12

    There is a wealth of information indicating that the hippocampal formation is important for learning and memory consolidation. The hippocampus is very sensitive to ageing and developmentally stressful factors such as prenatal malnutrition, which produces anatomical alterations of hippocampal pyramidal cells as well as impaired spatial learning. On the other hand, there are no reports about differential effects of postnatal malnutrition, installed at birth and maintained all through life in young and aged rats, on learning and memory of active avoidance, a task with an important procedural component. We now report that learning and long-term retention of this task were impaired in young malnourished animals, but not in young control, senile control, and senile malnourished Sprague-Dawley rats; young and senile rats were 90 and 660 days of age, respectively. Extinction tests showed, however, that long-term memory of the malnourished groups and senile control animals is impaired as compared with the young control animals. These data strongly suggest that the learning and long-term retention impairments seen in the young animals were due to postnatal malnutrition; in the senile groups, this cognitive alteration did not occur, probably because ageing itself is an important factor that enables the brain to engage in compensatory mechanisms that reduce the effects of malnutrition. Nonetheless, ageing and malnutrition, conditions known to produce anatomic and functional hippocampal alterations, impede the maintenance of long-term memory, as seen during the extinction test.

  19. Altered consolidation of extinction-like inhibitory learning in genotype-specific dysfunctional coping fostered by chronic stress in mice.

    PubMed

    Campus, P; Maiolati, M; Orsini, C; Cabib, S

    2016-12-15

    Genetic and stress-related factors interact to foster mental disorders, possibly through dysfunctional learning. In a previous study we reported that a temporary experience of reduced food availability increases forced swim (FS)-induced helplessness tested 14days after a first experience in mice of the standard inbred C57BL/6(B6) strain but reduces it in mice of the genetically unrelated DBA/2J (D2) strain. Because persistence of FS-induced helplessness influences adaptive coping with stress challenge and involve learning processes the present study tested whether the behavioral effects of restricted feeding involved altered consolidation of FS-related learning. First, we demonstrated that restricted feeding does not influence behavior expressed on the first FS experience, supporting a specific effect on persistence rather then development of helplessness. Second, we found that FS-induced c-fos expression in the infralimbic cortex (IL) was selectively enhanced in food-restricted (FR) B6 mice and reduced in FR D2 mice, supporting opposite alterations of consolidation processes involving this brain area. Third, we demonstrated that immediate post-FS inactivation of IL prevents 24h retention of acquired helplessness by continuously free-fed mice of both strains, indicating the requirement of a functioning IL for consolidation of FS-related learning in either mouse strain. Finally, in line with the known role of IL in consolidation of extinction memories, we found that restricted feeding selectively facilitated 24h retention of an acquired extinction in B6 mice whereas impairing it in D2 mice. These findings support the conclusion that an experience of reduced food availability strain-specifically affects persistence of newly acquired passive coping strategies by altering consolidation of extinction-like inhibitory learning.

  20. AX+, BX- Discrimination Learning in the Fear-Potentiated Startle Paradigm: Possible Relevance to Inhibitory Fear Learning in Extinction

    ERIC Educational Resources Information Center

    Myers, Karyn M.; Davis, Michael

    2004-01-01

    The neural mechanisms of fear suppression most commonly are studied through the use of extinction, a behavioral procedure in which a feared stimulus (i.e., one previously paired with shock) is nonreinforced repeatedly, leading to a reduction or elimination of the fear response. Although extinction is perhaps the most convenient index of fear…

  1. AX+, BX- Discrimination Learning in the Fear-Potentiated Startle Paradigm: Possible Relevance to Inhibitory Fear Learning in Extinction

    ERIC Educational Resources Information Center

    Myers, Karyn M.; Davis, Michael

    2004-01-01

    The neural mechanisms of fear suppression most commonly are studied through the use of extinction, a behavioral procedure in which a feared stimulus (i.e., one previously paired with shock) is nonreinforced repeatedly, leading to a reduction or elimination of the fear response. Although extinction is perhaps the most convenient index of fear…

  2. Amphibian decline and extinction: what we know and what we need to learn.

    PubMed

    Collins, James P

    2010-11-01

    For over 350 million yr, thousands of amphibian species have lived on Earth. Since the 1980s, amphibians have been disappearing at an alarming rate, in many cases quite suddenly. What is causing these declines and extinctions? In the modern era (post 1500) there are 6 leading causes of biodiversity loss in general, and all of these acting alone or together are responsible for modern amphibian declines: commercial use; introduced/exotic species that compete with, prey on, and parasitize native frogs and salamanders; land use change; contaminants; climate change; and infectious disease. The first 3 causes are historical in the sense that they have been operating for hundreds of years, although the rate of change due to each accelerated greatly after about the mid-20th century. Contaminants, climate change, and emerging infectious diseases are modern causes suspected of being responsible for the so-called 'enigmatic decline' of amphibians in protected areas. Introduced/exotic pathogens, land use change, and infectious disease are the 3 causes with a clear role in amphibian decline as well as extinction; thus far, the other 3 causes are only implicated in decline and not extinction. The present work is a review of the 6 causes with a focus on pathogens and suggested areas where new research is needed. Batrachochytrium dendrobatidis (Bd) is a chytrid fungus that is an emerging infectious disease causing amphibian population decline and species extinction. Historically, pathogens have not been seen as a major cause of extinction, but Bd is an exception, which is why it is such an interesting, important pathogen to understand. The late 20th and early 21st century global biodiversity loss is characterized as a sixth extinction event. Amphibians are a striking example of these losses as they disappear at a rate that greatly exceeds historical levels. Consequently, modern amphibian decline and extinction is a lens through which we can view the larger story of biodiversity

  3. Effects of prior cocaine versus morphine or heroin self-administration on extinction learning driven by over-expectation versus omission of reward

    PubMed Central

    Lucantonio, Federica; Kambhampati, S; Haney, Richard Z; Atalayer, Deniz; Rowland, Neil E; Shaham, Yavin; Schoenbaum, Geoffrey

    2014-01-01

    Background Addiction is characterized by an inability to stop using drugs, despite adverse consequences. One contributing factor to this compulsive drug taking could be the impact of drug use on the ability to extinguish drug seeking after changes in expected outcomes. Here we compared effects of cocaine, morphine, and heroin self-administration on two forms of extinction learning: standard extinction driven by reward omission and extinction driven by reward over-expectation. Methods In Experiment 1, we trained rats to self-administer cocaine, morphine, or sucrose for 3 hr/day (limited access). In Experiment 2, we trained rats to self-administer heroin or sucrose for 12 hr/day (extended access). Three weeks later, we trained the rats to associate several cues with palatable food reward, after which we assessed extinction of the learned Pavlovian response, first by pairing two cues together in the over-expectation procedure and later by omitting the food reward. Results Rats trained under limited access conditions to self-administer sucrose or morphine demonstrated normal extinction in response to both over-expectation and reward omission, whereas cocaine-experienced rats or rats trained to self-administer heroin under extended access conditions exhibited normal extinction in response to reward omission but failed to show extinction in response to over-expectation. Conclusions The specific long-lasting effects of cocaine and heroin show that drug exposure induces long-lasting deficits in the ability to extinguish reward seeking after changes in expected outcomes. These deficits were not observed in a standard extinction procedure but instead only affected extinction learning driven by a more complex phenomenon of over-expectation. PMID:25641634

  4. Effects of prior cocaine versus morphine or heroin self-administration on extinction learning driven by overexpectation versus omission of reward.

    PubMed

    Lucantonio, Federica; Kambhampati, Sarita; Haney, Richard Z; Atalayer, Deniz; Rowland, Neil E; Shaham, Yavin; Schoenbaum, Geoffrey

    2015-05-15

    Addiction is characterized by an inability to stop using drugs, despite adverse consequences. One contributing factor to this compulsive drug taking could be the impact of drug use on the ability to extinguish drug seeking after changes in expected outcomes. Here, we compared effects of cocaine, morphine, and heroin self-administration on two forms of extinction learning: standard extinction driven by reward omission and extinction driven by reward overexpectation. In experiment 1, we trained rats to self-administer cocaine, morphine, or sucrose for 3 hours per day (limited access). In experiment 2, we trained rats to self-administer heroin or sucrose for 12 hours per day (extended access). Three weeks later, we trained the rats to associate several cues with palatable food reward, after which we assessed extinction of the learned Pavlovian response, first by pairing two cues together in the overexpectation procedure and later by omitting the food reward. Rats trained under limited access conditions to self-administer sucrose or morphine demonstrated normal extinction in response to both overexpectation and reward omission, whereas cocaine-experienced rats or rats trained to self-administer heroin under extended access conditions exhibited normal extinction in response to reward omission but failed to show extinction in response to overexpectation. Here we show that cocaine and heroin can induce long-lasting deficits in the ability to extinguish reward seeking. These deficits were not observed in a standard extinction procedure but instead only affected extinction learning driven by a more complex phenomenon of overexpectation. Published by Elsevier Inc.

  5. Adolescents exhibit behavioral differences from adults during instrumental learning and extinction

    PubMed Central

    Sturman, David A.; Mandell, Daniel R.; Moghaddam, Bita

    2010-01-01

    Adolescence is associated with the development of brain regions linked to cognition and emotion. Such changes are thought to contribute to the behavioral and neuropsychiatric vulnerabilities of this period. We compared adolescent (P28-42) and adult (P60+) rats as they performed a simple instrumental task and extinction. Animals were trained to poke into a hole for a food-pellet reinforcer. After six days of training, animals underwent extinction sessions in which the previously rewarded behavior was no longer reinforced. During extinction we examined the effects of continued presentation of a cue light and food restriction. Adults and adolescents exhibited similar performance during training, although adolescents made more task-irrelevant pokes, consistent with increased exploration. Adults made more premature pokes, which could indicate a more exclusive focus on the task. During extinction, adolescents made more perseverative (previously reinforced) pokes than adults. This behavior was strongly modulated by the combination of motivational factors present (food restriction and cue light), indicating that adolescents were differentially sensitive to them. Furthermore, food restriction induced greater open-field activity in adolescents but not adults. Thus, as the neural circuitry of motivated behavior develops substantially during adolescence, so too does the behavioral sensitivity to motivational factors. Understanding how such factors differently affect adolescents may shed light on mechanisms that lead to the development of disorders that are manifested during this period. PMID:20141277

  6. Evaluative differential conditioning of disgust: a sticky form of relational learning that is resistant to extinction.

    PubMed

    Olatunji, Bunmi O; Forsyth, John P; Cherian, Ancy

    2007-01-01

    The present study sought to (a) test whether autonomic (i.e., electrodermal) and evaluative conditioning can be differentially established to verbal CSs, and (b) whether extinction procedures can reliably attenuate differential conditioned evaluative responding. Thirty undergraduates underwent a 10-min adaptation period followed by three consecutive conditioning phases: habituation, acquisition, and extinction. Conditioning involved participants viewing two semi-randomly presented words on a computer monitor. During acquisition, one word (CS+) was reliably paired 12 times with the UCS (pictorial stimuli depicting bodily mutilation), whereas the remaining word (CS-) was presented 12 times and reliably followed by neutral pictures (inanimate common objects). As predicted, electrodermal and evaluative responses during acquisition were of larger magnitude to the CS+ compared to the CS-. During extinction, participants continued to evaluate the CS+ as more disgusting relative to the CS-, whereas distress and fear-related emotional ratings attenuated across extinction trials. The implications of these findings for the modifiability of disgust-based evaluative responses in specific anxiety disorders will be discussed.

  7. Adolescents exhibit behavioral differences from adults during instrumental learning and extinction.

    PubMed

    Sturman, David A; Mandell, Daniel R; Moghaddam, Bita

    2010-02-01

    Adolescence is associated with the development of brain regions linked to cognition and emotion. Such changes are thought to contribute to the behavioral and neuropsychiatric vulnerabilities of this period. We compared adolescent (Postnatal Days 28-42) and adult (Postnatal Day 60+) rats as they performed a simple instrumental task and extinction. Rats were trained to poke into a hole for a food-pellet reinforcer. After six days of training, rats underwent extinction sessions in which the previously rewarded behavior was no longer reinforced. During extinction, we examined the effects of continued presentation of a cue light and food restriction. Adults and adolescents exhibited similar performance during training, although adolescents made more task-irrelevant pokes, consistent with increased exploration. Adults made more premature pokes, which could indicate a more exclusive focus on the task. During extinction, adolescents made more perseverative (previously reinforced) pokes than adults. This behavior was strongly modulated by the combination of motivational factors present (food restriction and cue light), indicating that adolescents were differentially sensitive to them. Furthermore, food restriction induced greater open-field activity in adolescents but not in adults. Thus, as the neural circuitry of motivated behavior develops substantially during adolescence, so too does the behavioral sensitivity to motivational factors. Understanding how such factors differently affect adolescents may shed light on mechanisms that lead to the development of disorders that are manifested during this period.

  8. Activation of the Infralimbic Cortex in a Fear Context Enhances Extinction Learning

    ERIC Educational Resources Information Center

    Thompson, Brittany M.; Baratta, Michael V.; Biedenkapp, Joseph C.; Rudy, Jerry W.; Watkins, Linda R.; Maier, Steven F.

    2010-01-01

    Activation of the infralimbic region (IL) of the medial prefrontal cortex (mPFC) reduces conditioned fear in a variety of situations, and the IL is thought to play an important role in the extinction of conditioned fear. Here we report a series of experiments using contextual fear conditioning in which the IL is activated with the GABAa antagonist…

  9. Extinction, Spontaneous Recovery and Renewal of Flavor Preferences Based on Taste-Taste Learning

    ERIC Educational Resources Information Center

    Diaz, Estrella; De la Casa, L. G.

    2011-01-01

    This paper presents evidence of extinction, spontaneous recovery and renewal in a conditioned preferences paradigm based on taste-taste associations. More specifically, in three experiments rats exposed to a simultaneous compound of citric acid-saccharin solution showed a preference for the citric solution when the preference was measured with a…

  10. Activation of the Infralimbic Cortex in a Fear Context Enhances Extinction Learning

    ERIC Educational Resources Information Center

    Thompson, Brittany M.; Baratta, Michael V.; Biedenkapp, Joseph C.; Rudy, Jerry W.; Watkins, Linda R.; Maier, Steven F.

    2010-01-01

    Activation of the infralimbic region (IL) of the medial prefrontal cortex (mPFC) reduces conditioned fear in a variety of situations, and the IL is thought to play an important role in the extinction of conditioned fear. Here we report a series of experiments using contextual fear conditioning in which the IL is activated with the GABAa antagonist…

  11. Extinction, Spontaneous Recovery and Renewal of Flavor Preferences Based on Taste-Taste Learning

    ERIC Educational Resources Information Center

    Diaz, Estrella; De la Casa, L. G.

    2011-01-01

    This paper presents evidence of extinction, spontaneous recovery and renewal in a conditioned preferences paradigm based on taste-taste associations. More specifically, in three experiments rats exposed to a simultaneous compound of citric acid-saccharin solution showed a preference for the citric solution when the preference was measured with a…

  12. The Metabotropic Glutamate Receptor, mGlu5, Is Required for Extinction Learning That Occurs in the Absence of a Context Change

    PubMed Central

    André, Marion Agnes Emma; Güntürkün, Onur; Manahan-Vaughan, Denise

    2015-01-01

    The metabotropic glutamate (mGlu) receptors and, in particular, mGlu5 are crucially involved in multiple forms of synaptic plasticity that are believed to underlie explicit memory. MGlu5 is also required for information transfer through neuronal oscillations and for spatial memory. Furthermore, mGlu5 is involved in extinction of implicit forms of learning. This places this receptor in a unique position with regard to information encoding. Here, we explored the role of this receptor in context-dependent extinction learning under constant, or changed, contextual conditions. Animals were trained over 3 days to take a left turn under 25% reward probability in a T-maze with a distinct floor pattern (Context A). On Day 4, they experienced either a floor pattern change (Context B) or the same floor pattern (Context A) in the absence of reward. After acquisition of the task, the animals were returned to the maze once more on Day 5 (Context A, no reward). Treatment with the mGlu5 antagonist, 2-methyl-6-(phenylethynyl) pyridine, before maze exposure on Day 4 completely inhibited extinction learning in the AAA paradigm but had no effect in the ABA paradigm. A subsequent return to the original context (A, on Day 5) revealed successful extinction in the AAA paradigm, but impairment of extinction in the ABA paradigm. These data support that although extinction learning in a new context is unaffected by mGlu5 antagonism, extinction of the consolidated context is impaired. This suggests that mGlu5 is intrinsically involved in enabling learning that once-relevant information is no longer valid. © 2014 The Authors. Hippocampus Published by Wiley Periodicals, Inc. PMID:25160592

  13. The metabotropic glutamate receptor, mGlu5, is required for extinction learning that occurs in the absence of a context change.

    PubMed

    André, Marion Agnes Emma; Güntürkün, Onur; Manahan-Vaughan, Denise

    2015-02-01

    The metabotropic glutamate (mGlu) receptors and, in particular, mGlu5 are crucially involved in multiple forms of synaptic plasticity that are believed to underlie explicit memory. MGlu5 is also required for information transfer through neuronal oscillations and for spatial memory. Furthermore, mGlu5 is involved in extinction of implicit forms of learning. This places this receptor in a unique position with regard to information encoding. Here, we explored the role of this receptor in context-dependent extinction learning under constant, or changed, contextual conditions. Animals were trained over 3 days to take a left turn under 25% reward probability in a T-maze with a distinct floor pattern (Context A). On Day 4, they experienced either a floor pattern change (Context B) or the same floor pattern (Context A) in the absence of reward. After acquisition of the task, the animals were returned to the maze once more on Day 5 (Context A, no reward). Treatment with the mGlu5 antagonist, 2-methyl-6-(phenylethynyl) pyridine, before maze exposure on Day 4 completely inhibited extinction learning in the AAA paradigm but had no effect in the ABA paradigm. A subsequent return to the original context (A, on Day 5) revealed successful extinction in the AAA paradigm, but impairment of extinction in the ABA paradigm. These data support that although extinction learning in a new context is unaffected by mGlu5 antagonism, extinction of the consolidated context is impaired. This suggests that mGlu5 is intrinsically involved in enabling learning that once-relevant information is no longer valid.

  14. Are extinction opinions extinct?

    PubMed Central

    2017-01-01

    Extinction models vary in the information they require, the simplest considering the rate of certain sightings only. More complicated methods include uncertain sightings and allow for variation in the reliability of uncertain sightings. Generally extinction models require expert opinion, either as a prior belief that a species is extinct, or to establish the quality of a sighting record, or both. Is this subjectivity necessary? We present two models to explore whether the individual quality of sightings, judged by experts, is strongly informative of the probability of extinction: the ‘quality breakpoint method’ and the ‘quality as variance method’. For the first method we use the Barbary lion as an exemplar. For the second method we use the Barbary lion, Alaotra grebe, Jamaican petrel and Pohnpei starling as exemplars. The ‘quality breakpoint method’ uses certain and uncertain sighting records, and the quality of uncertain records, to establish whether a change point in the rate of sightings can be established using a simultaneous Bayesian optimisation with a non-informative prior. For the Barbary lion, there is a change in subjective quality of sightings around 1930. Unexpectedly sighting quality increases after this date. This suggests that including quality scores from experts can lead to irregular effects and may not offer reliable results. As an alternative, we use quality as a measure of variance around the sightings, not a change in quality. This leads to predictions with larger standard deviations, however the results remain consistent across any prior belief of extinction. Nonetheless, replacing actual quality scores with random quality scores showed little difference, inferring that the quality scores from experts are superfluous. Therefore, we deem the expensive process of obtaining pooled expert estimates as unnecessary, and even when used we recommend that sighting data should have minimal input from experts in terms of assessing the

  15. mGlu5 Receptors and Relapse to Cocaine-Seeking: The Role of Receptor Trafficking in Postrelapse Extinction Learning Deficits.

    PubMed

    Knackstedt, Lori A; Schwendt, Marek

    2016-01-01

    We have previously demonstrated that MTEP, an allosteric antagonist of mGlu5, infused into the nucleus accumbens attenuates relapse after abstinence from cocaine self-administration. MTEP infused into the dorsolateral striatum (dlSTR) does not alter relapse but has long-lasting effects on subsequent extinction learning. Here we tested whether systemic MTEP would prevent relapse after abstinence or alter extinction learning. We also investigated the mechanism of action by which intra-dlSTR MTEP on test day alters extinction on subsequent days. Animals self-administered cocaine for 12 days followed by abstinence for 20-21 days. MTEP (0.5-5 mg/kg IP) was administered prior to placement into the operant chamber for a context-primed relapse test. A separate group of animals received intra-dlSTR MTEP prior to the relapse test and were sacrificed day later. Systemic administration of MTEP attenuated abstinent-relapse without significantly affecting extinction learning. Surface biotinylation analysis of protein expression in the dlSTR revealed that, in cocaine animals, intra-dlSTR MTEP administration decreased mGlu5 surface expression and prevented changes in Arc and GluA1/GluA2 observed in their vehicle counterparts. Thus, blockade of mGlu5 receptors may be utilized in future treatment strategies for relapse prevention in humans, although the effects of chronic blockade on extinction learning should be further evaluated.

  16. Relationship of delay aversion and response inhibition to extinction learning, aggression, and sexual behaviour.

    PubMed

    Van den Bergh, Filip; Spronk, Marjolein; Ferreira, Leila; Bloemarts, Emilie; Groenink, Lucianne; Olivier, Berend; Oosting, Ronald

    2006-11-25

    Impulsivity is an important symptom of many psychiatric disorders, and can be divided into two subtypes: response inhibition deficits and delay aversion. In the present study, we investigated the relationship between delay aversion and response inhibition, both to each other and to locomotion, extinction of conditioned responses, sexual behaviour, and aggressive behaviour. To that end, we quantified the behaviour of 24 rats in several tests. To measure response inhibition, rats were trained in a stop-signal task. In this operant task, rats were rewarded food if they inhibited execution of a response after presentation of an audible stop-signal. Delay aversion was measured in an operant task in which rats made a choice between a small, immediately available reward and a large reward available after a delay. The results showed that delay aversion and response inhibition were independent. Responses during extinction and various measures of aggressive behaviour were positively correlated to delay aversion. The speed of go-trials in the stop-task was correlated to non-aggressive behaviour. We conclude that the role of response inhibition in various behaviours is small, but delay aversion in particular contributes to several other behaviours, such as aggressive behaviour and extinction.

  17. Learning and extinction of conditioned hearing sensation change in the beluga whale (Delphinapterus leucas).

    PubMed

    Nachtigall, Paul E; Supin, Alexander Ya; Estaban, Jose-Antonio; Pacini, Aude F

    2016-02-01

    Ice-dwelling beluga whales are increasingly being exposed to anthropogenic loud sounds. Beluga's hearing sensitivity measured during a warning sound just preceding a loud sound was tested using pip-train stimuli and auditory evoked potential recording. When the test/warning stimulus with a frequency of 32 or 45 kHz preceded the loud sound with a frequency of 32 kHz and a sound pressure level of 153 dB re 1 μPa, 2 s, hearing thresholds before the loud sound increased relative to the baseline. The threshold increased up to 15 dB for the test frequency of 45 kHz and up to 13 dB for the test frequency of 32 kHz. These threshold increases were observed during two sessions of 36 trials each. Extinction tests revealed no change during three experimental sessions followed by a jump-like return to baseline thresholds. The low exposure level producing the hearing-dampening effect (156 dB re 1 µPa(2)s in each trial), and the manner of extinction, may be considered as evidence that the observed hearing threshold increases were a demonstration of conditioned dampening of hearing when the whale anticipated the quick appearance of a loud sound in the same way demonstrated in the false killer whale and bottlenose dolphin.

  18. Deficient inhibitory processing in trait anxiety: Evidence from context-dependent fear learning, extinction recall and renewal.

    PubMed

    Haaker, J; Lonsdorf, T B; Schümann, D; Menz, M; Brassen, S; Bunzeck, N; Gamer, M; Kalisch, R

    2015-10-01

    Impaired fear inhibition has been described as a hallmark of pathological anxiety. We aimed at further characterizing the relation between fear inhibition and anxiety by extending previous work to contextual safety stimuli as well as to dimensional scores of trait anxiety in a large sample. We employed a validated paradigm for context-dependent fear acquisition/extinction (day 1) and retrieval/expression (day 2) in 377 healthy individuals. This large sample size allowed the employment of a dimensional rather than binary approach with respect to individual differences in trait anxiety. We observed a positive correlation on day 1 between trait anxiety with all CSs that possess an inherent inhibitory component, conveyed either by reliable non-reinforcement of a specific CS in a dangerous context (safe cue) or by the context itself (i.e., safe context). No correlation however was observed for a CS that possesses excitatory (threatening) properties only. These results were observed during fear learning (day 1) for US expectancy and fear ratings but not for SCRs. No such pattern was evident during fear and extinction retrieval/expression (day 2). We provide further evidence that high trait anxiety is associated with the inability to take immediate advantage of environmental safety cues (cued and contextual), which might represent a promising trans-diagnostic marker for different anxiety disorders. Consequently, the incorporation of methods to optimize inhibitory learning in current cognitive behavioral therapy (CBT) treatments might open up a promising avenue for precision medicine in anxiety disorders. We did not include patients diagnosed with anxiety disorders. Copyright © 2015. Published by Elsevier B.V.

  19. Neuronal circuits of fear extinction.

    PubMed

    Herry, Cyril; Ferraguti, Francesco; Singewald, Nicolas; Letzkus, Johannes J; Ehrlich, Ingrid; Lüthi, Andreas

    2010-02-01

    Fear extinction is a form of inhibitory learning that allows for the adaptive control of conditioned fear responses. Although fear extinction is an active learning process that eventually leads to the formation of a consolidated extinction memory, it is a fragile behavioural state. Fear responses can recover spontaneously or subsequent to environmental influences, such as context changes or stress. Understanding the neuronal substrates of fear extinction is of tremendous clinical relevance, as extinction is the cornerstone of psychological therapy of several anxiety disorders and because the relapse of maladaptative fear and anxiety is a major clinical problem. Recent research has begun to shed light on the molecular and cellular processes underlying fear extinction. In particular, the acquisition, consolidation and expression of extinction memories are thought to be mediated by highly specific neuronal circuits embedded in a large-scale brain network including the amygdala, prefrontal cortex, hippocampus and brain stem. Moreover, recent findings indicate that the neuronal circuitry of extinction is developmentally regulated. Here, we review emerging concepts of the neuronal circuitry of fear extinction, and highlight novel findings suggesting that the fragile phenomenon of extinction can be converted into a permanent erasure of fear memories. Finally, we discuss how research on genetic animal models of impaired extinction can further our understanding of the molecular and genetic bases of human anxiety disorders.

  20. Updating Watson & Marks (1971): How Has Our Understanding of the Mechanisms of Extinction Learning Evolved and Where Is Our Field Going Next?

    PubMed

    Asnaani, Anu; McLean, Carmen P; Foa, Edna B

    2016-09-01

    J. P. Watson and I. M. Marks published a seminal article in Behavior Therapy entitled "Relevant and Irrelevant Fear in Flooding-A Crossover Study of Phobic Patients" in 1971 that paved the way for important theoretical developments and empirical studies that examined the mechanisms underlying extinction learning. Indeed, in the 44 years since their article was published, our knowledge about how exposure therapy works has increased considerably. In this review, we explore the progress our field has made in understanding extinction learning and how Watson and Marks' important work has influenced this progress. We provide a brief summary of the design and major findings of the Watson and Marks (1971) study, followed by a brief description of several theoretical conceptualizations of fear extinction that were developed following the article's publication. We also review empirical studies that illustrate the "state of the science" with regard to the following key issues that were explored in Watson and Marks' paper: (a) the effect of specificity of exposure stimuli content in exposure therapy on outcome; (b) fear activation as a mechanism of exposure; and (c) the associations between within- and between-session extinction learning and treatment outcome. The major findings of these three issues over the past 4 decades are summarized and discussed.

  1. Stimulation of the Noradrenergic System during Memory Formation Impairs Extinction Learning but not the Disruption of Reconsolidation

    PubMed Central

    Soeter, Marieke; Kindt, Merel

    2012-01-01

    The noradrenergic system plays a critical role in the ‘consolidation' of emotional memory. If we are to target ‘reconsolidation' in patients with anxiety disorders, the noradrenergic strengthening of fear memory should not impair the disruption of reconsolidation. In Experiment I, we addressed this issue using a differential fear conditioning procedure allowing selective reactivation of one of two fear associations. First, we strengthened fear memory by administering an α2-adrenergic receptor antagonist (ie, yohimbine HCl; double-blind placebo-controlled study) 30 min before acquisition (time for peak value yohimbine HCl <1 h). Next, the reconsolidation of one of the fear associations was manipulated by administering a β-adrenergic receptor antagonist (ie, propranolol HCl) 90 min before its selective reactivation (time for peak value propranolol HCl <2 h). In Experiment II, we administered propranolol HCl after reactivation of the memory to rule out a possible effect of the pharmacological manipulation on the memory retrieval itself. The excessive release of noradrenaline during memory formation not only delayed the process of extinction 48 h later, but also triggered broader fear generalization. Yet, the β-adrenergic receptor blocker during reconsolidation selectively ‘neutralized' the fear-arousing aspects of the noradrenergic-strengthened memory and undermined the generalization of fear. We observed a similar reduction in fear responding when propranolol HCl was administered after reactivation of the memory. The present findings demonstrate the involvement of noradrenergic modulation in the formation as well as generalization of human fear memory. Given that the noradrenergic strengthening of fear memory impaired extinction learning but not the disruption of reconsolidation, our findings may have implications for the treatment of anxiety disorders. PMID:22169947

  2. The role of ventral and dorsal striatum mGluR5 in relapse to cocaine-seeking and extinction learning.

    PubMed

    Knackstedt, Lori A; Trantham-Davidson, Heather L; Schwendt, Marek

    2014-01-01

    Cocaine addiction is a chronic, relapsing disease characterized by an inability to regulate drug-seeking behavior. Here we investigated the role of mGluR5 in the ventral and dorsal striatum in regulating cocaine-seeking following both abstinence and extinction. Animals underwent 2 weeks of cocaine self-administration followed by 3 weeks of home-cage abstinence. Animals were then reintroduced to the operant chamber for a context-induced relapse test, followed by 7-10 days of extinction training. Once responding was extinguished, cue-primed reinstatement test was conducted. Both drug-seeking tests were conducted in the presence of either mGluR5 negative allosteric modulator, MTEP or vehicle infused into either the nucleus accumbens (NA) core or dorsolateral striatum (dSTR). We found that MTEP infused in the NA core attenuated both context-induced relapse following abstinence and cue-primed reinstatement following extinction training. Blocking dSTR mGluR5 had no effect on context- or cue-induced cocaine-seeking. However, the intra-dSTR MTEP infusion on the context-induced relapse test day attenuated extinction learning for 4 days after the infusion. Furthermore, mGluR5 surface expression was reduced and LTD was absent in dSTR slices of animals undergoing 3 weeks of abstinence from cocaine but not sucrose self-administration. LTD was restored by bath application of VU-29, a positive allosteric modulator of mGluR5. Bath application of MTEP prevented the induction of LTD in dSTR slices from sucrose animals. Taken together, this data indicates that dSTR mGluR5 plays an essential role in extinction learning but not cocaine relapse, while NA core mGluR5 modulates drug-seeking following both extinction and abstinence from cocaine self-administration. © 2013 Society for the Study of Addiction.

  3. Extinction and Latent Inhibition Involve a Similar Form of Inhibitory Learning that is Stored in and Retrieved from the Infralimbic Cortex.

    PubMed

    Lingawi, Nura W; Westbrook, R Fredrick; Laurent, Vincent

    2016-10-20

    Extinction and latent inhibition each refer to a reduction in conditioned responding: the former occurs when pairings of a conditioned stimulus (CS) and an unconditioned stimulus (US) are followed by repeated presentations of the CS alone; the latter occurs when CS alone presentations precede its pairings with the US. The present experiments used fear conditioning to test the hypothesis that both phenomena involve a similar form of inhibitory learning that recruits common neuronal substrates. We found that the initial inhibitory memory established by extinction is reactivated in the infralimbic (IL) cortex during additional extinction. Remarkably, this reactivation also occurs when the initial inhibitory memory had been established by latent inhibition. In both cases, the inhibitory memory was strengthened by pharmacological stimulation of the IL. Moreover, NMDA receptor blockade in the IL disrupted the weakening in conditioned responding produced by either latent inhibition or extinction. These findings, therefore, indicate that latent inhibition and extinction produce a similar inhibitory memory that is retrieved from the IL. They also demonstrate that the IL plays a wide role in fear regulation by promoting the retrieval of inhibitory memories generated by CS alone presentations either before or after this CS has been rendered dangerous.

  4. Beta-adrenergic receptors support attention to extinction learning that occurs in the absence, but not the presence, of a context change

    PubMed Central

    André, Marion Agnès Emma; Wolf, Oliver T.; Manahan-Vaughan, Denise

    2015-01-01

    The noradrenergic (NA)-system is an important regulator of cognitive function. It contributes to extinction learning (EL), and in disorders where EL is impaired NA-dysfunction has been postulated. We explored whether NA acting on beta-adrenergic-receptors (β-AR), regulates EL that depends on context, but is not fear-associated. We assessed behavior in an “AAA” or “ABA” paradigm: rats were trained for 3 days in a T-maze (context-A) to learn that a reward is consistently found in the goal arm, despite low reward probability. This was followed on day 4 by EL (unrewarded), whereby in the ABA-paradigm, EL was reinforced by a context change (B), and in the AAA-paradigm, no context change occurred. On day 5, re-exposure to the A-context (unrewarded) occurred. Typically, in control “AAA” animals EL occurred on day 4 that progressed further on day 5. In control “ABA” animals, EL also occurred on day 4, followed by renewal of the previously learned (A) behavior on day 5, that was succeeded (on day 5) by extinction of this behavior, as the animals realised that no food reward would be given. Treatment with the β-AR-antagonist, propranolol, prior to EL on day 4, impaired EL in the AAA-paradigm. In the “ABA” paradigm, antagonist treatment on day 4, had no effect on extinction that was reinforced by a context change (B). Furthermore, β-AR-antagonism prior to renewal testing (on day 5) in the ABA-paradigm, resulted in normal renewal behavior, although subsequent extinction of responses during day 5 was prevented by the antagonist. Thus, under both treatment conditions, β-AR-antagonism prevented extinction of the behavior learned in the “A” context. β-AR-blockade during an overt context change did not prevent EL, whereas β-AR were required for EL in an unchanging context. These data suggest that β-AR may support EL by reinforcing attention towards relevant changes in the previously learned experience, and that this process supports extinction

  5. Genetic Inactivation of D-Amino Acid Oxidase Enhances Extinction and Reversal Learning in Mice

    ERIC Educational Resources Information Center

    Labrie, Viviane; Duffy, Steven; Wang, Wei; Barger, Steven W.; Baker, Glen B.; Roder, John C.

    2009-01-01

    Activation of the N-methyl-d-aspartate receptor (NMDAR) glycine site has been shown to accelerate adaptive forms of learning that may benefit psychopathologies involving cognitive and perseverative disturbances. In this study, the effects of increasing the brain levels of the endogenous NMDAR glycine site agonist D-serine, through the genetic…

  6. Zinc Transporter 3 Is Involved in Learned Fear and Extinction, but Not in Innate Fear

    ERIC Educational Resources Information Center

    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,…

  7. Genetic Inactivation of D-Amino Acid Oxidase Enhances Extinction and Reversal Learning in Mice

    ERIC Educational Resources Information Center

    Labrie, Viviane; Duffy, Steven; Wang, Wei; Barger, Steven W.; Baker, Glen B.; Roder, John C.

    2009-01-01

    Activation of the N-methyl-d-aspartate receptor (NMDAR) glycine site has been shown to accelerate adaptive forms of learning that may benefit psychopathologies involving cognitive and perseverative disturbances. In this study, the effects of increasing the brain levels of the endogenous NMDAR glycine site agonist D-serine, through the genetic…

  8. Facing Extinction: Organizational Learning in a Small Secondary School under Duress

    ERIC Educational Resources Information Center

    Symons, Cam

    2005-01-01

    This study examined the process of organizational learning in a small secondary school in a company town during a protracted period of turbulence, arising from the downsizing of the community's main employer. The hypothesis was that distributed leadership among school staff created a change in teaching practices from a limited repertoire of…

  9. Facing Extinction: Organizational Learning in a Small Secondary School under Duress

    ERIC Educational Resources Information Center

    Symons, Cam

    2005-01-01

    This study examined the process of organizational learning in a small secondary school in a company town during a protracted period of turbulence, arising from the downsizing of the community's main employer. The hypothesis was that distributed leadership among school staff created a change in teaching practices from a limited repertoire of…

  10. Zinc Transporter 3 Is Involved in Learned Fear and Extinction, but Not in Innate Fear

    ERIC Educational Resources Information Center

    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,…

  11. Valproic acid but not D-cycloserine facilitates sleep-dependent offline learning of extinction and habituation of conditioned fear in humans.

    PubMed

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

    2013-01-01

    The effectiveness of D-cycloserine (DCS), an N-methyl-D-aspartate glutamate receptor partial agonist, and valproic acid (VPA), a histone deacetylase inhibitor, in facilitating the extinction of fear-conditioned memory has been explored in humans and animals. Here, we confirmed whether DCS (100 mg) and VPA (400 mg) act in off-line learning processes during sleep or waking, for further clinical application to anxiety disorders and posttraumatic stress disorder (PTSD). We performed a randomized, blind, placebo-controlled clinical trial in 90 healthy adults. Visual cues and electric shocks were used as the conditioned stimulus (CS) and unconditioned stimulus (US), respectively. The extinction effect was observed not in simple recall after the extinction of coupled CS-US, but was observed in the post-re-exposure phase after unexpected re-exposure to reinstatement CS-US coupling. Newly acquired conditioned fear was also eliminated or habituated by DCS and VPA administration, in line with previous findings. Furthermore, VPA facilitated the off-line learning process of conditioned fear extinction and habituation during sleep, while DCS facilitated this process during waking. These novel findings suggest that DCS and VPA might enhance exposure-based cognitive therapy for anxiety disorders and PTSD by reducing the vulnerability to reinstatement and preventing relapses of fear-conditioned responses, and provide evidence for a peculiarity of the sleep-dependent off-line learning process for conditioned fear extinction. This article is part of a Special Issue entitled 'Cognitive Enhancers'. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. Extinction in multiple contexts: Effects on the rate of extinction and the strength of response recovery.

    PubMed

    Bustamante, Javier; Uengoer, Metin; Thorwart, Anna; Lachnit, Harald

    2016-09-01

    In two human predictive-learning experiments, we investigated the effects of extinction in multiple contexts on the rate of extinction and the strength of response recovery. In each experiment, participants initially received acquisition training with a target cue in one context, followed by extinction either in a different context (extinction in a single context) or in three different contexts (extinction in multiple contexts). The results of both experiments showed that conducting extinction in multiple contexts led to higher levels of responding during extinction than did extinction in a single context. Additionally, Experiment 2 showed that extinction in multiple contexts prevented ABC renewal but had no detectable impact on ABA renewal. Our results are discussed within the framework of contemporary learning theories of contextual control and extinction.

  13. Extinction with multiple excitors.

    PubMed

    McConnell, Bridget L; Miguez, Gonzalo; Miller, Ralph R

    2013-06-01

    Four conditioned suppression experiments with rats, using an ABC renewal design, investigated the effects of compounding the target conditioned excitor with additional, nontarget conditioned excitors during extinction. Experiment 1 showed stronger extinction, as evidenced by less renewal, when the target excitor was extinguished in compound with a second excitor, relative to when it was extinguished with associatively neutral stimuli. Critically, this deepened extinction effect was attenuated (i.e., more renewal occurred) when a third excitor was added during extinction training. This novel demonstration contradicts the predictions of associative learning models based on total error reduction, but it is explicable in terms of a counteraction effect within the framework of the extended comparator hypothesis. The attenuated deepened extinction effect was replicated in Experiments 2a and 3, which also showed that pretraining consisting of weakening the association between the two additional excitors (Experiments 2a and 2b) or weakening the association between one of the additional excitors and the unconditioned stimulus (Experiment 3) attenuated the counteraction effect, thereby resulting in a decrease in responding to the target excitor. These results suggest that more than simple total error reduction determines responding after extinction.

  14. A developmental analysis of threat/safety learning and extinction recall during middle childhood.

    PubMed

    Michalska, Kalina J; Shechner, Tomer; Hong, Melanie; Britton, Jennifer C; Leibenluft, Ellen; Pine, Daniel S; Fox, Nathan A

    2016-06-01

    The current study examined developmental changes in fear learning and generalization in 54 healthy 5-10-year old children using a novel fear conditioning paradigm. In this task, the conditioned stimuli (CS+/CS-) were two blue and yellow colored cartoon bells, and the unconditioned stimulus was an unpleasant loud alarm sound presented with a red cartoon bell. Physiological and subjective data were acquired. Three weeks after conditioning, 48 of these participants viewed the CS-, CS+, and morphed images resembling the CS+. Participants made threat-safety discriminations while appraising threat and remembering the CS+. Although no age-related differences in fear learning emerged, patterns of generalization were qualified by child age. Older children demonstrated better discrimination between the CS+ and CS morphs than younger age groups and also reported more fear to stimuli resembling the CS+ than younger children. Clinical implications and future directions are discussed. Copyright © 2016. Published by Elsevier Inc.

  15. Effects of Neonatal Amygdala Lesions on Fear Learning, Conditioned Inhibition, and Extinction in Adult Macaques

    PubMed Central

    Kazama, Andy M.; Heuer, Eric; Davis, Michael; Bachevalier, Jocelyne

    2013-01-01

    Fear conditioning studies have demonstrated the critical role played by the amygdala in emotion processing. Although all lesion studies until now investigated the effect of adult-onset damage on fear conditioning, the current study assessed fear-learning abilities, as measured by fear-potentiated startle, in adult monkeys that had received neonatal neurotoxic amygdala damage or sham-operations. After fear acquisition, their abilities to learn and use a safety cue to modulate their fear to the conditioned cue, and, finally, to extinguish their response to the fear conditioned cue were measured with the AX+/BX− Paradigm. Neonatal amygdala damage retarded, but did not completely abolish, the acquisition of a learned fear. After acquisition of the fear signal, four of the six animals with neonatal amygdala lesions discriminated between the fear and safety cues and were also able to use the safety signal to reduce the potentiated-startle response and to extinguish the fear response when the air-blast was absent. In conclusion, the present results support the critical contribution of the amygdala during the early phases of fear conditioning that leads to quick, robust responses to potentially threatening stimuli, a highly adaptive process across all species and likely to be present in early infancy. The neonatal amygdala lesions also indicated the presence of amygdala-independent alternate pathways that are capable to support fear learning in the absence of a functional amygdala. This parallel processing of fear responses within these alternate pathways was also sufficient to support the ability to flexibly modulate the magnitude of the fear responses. PMID:22642884

  16. Effects of neonatal amygdala lesions on fear learning, conditioned inhibition, and extinction in adult macaques.

    PubMed

    Kazama, Andy M; Heuer, Eric; Davis, Michael; Bachevalier, Jocelyne

    2012-06-01

    Fear conditioning studies have demonstrated the critical role played by the amygdala in emotion processing. Although all lesion studies until now investigated the effect of adult-onset damage on fear conditioning, the current study assessed fear-learning abilities, as measured by fear-potentiated startle, in adult monkeys that had received neonatal neurotoxic amygdala damage or sham-operations. After fear acquisition, their abilities to learn and use a safety cue to modulate their fear to the conditioned cue, and, finally, to extinguish their response to the fear conditioned cue were measured with the AX+/BX- Paradigm. Neonatal amygdala damage retarded, but did not completely abolish, the acquisition of a learned fear. After acquisition of the fear signal, four of the six animals with neonatal amygdala lesions discriminated between the fear and safety cues and were also able to use the safety signal to reduce the potentiated-startle response and to extinguish the fear response when the air-blast was absent. In conclusion, the present results support the critical contribution of the amygdala during the early phases of fear conditioning that leads to quick, robust responses to potentially threatening stimuli, a highly adaptive process across all species and likely to be present in early infancy. The neonatal amygdala lesions also indicated the presence of amygdala-independent alternate pathways that are capable to support fear learning in the absence of a functional amygdala. This parallel processing of fear responses within these alternate pathways was also sufficient to support the ability to flexibly modulate the magnitude of the fear responses. © 2012 American Psychological Association

  17. Effect of ethanolic extract of Acacia auriculiformis leaves on learning and memory in rats

    PubMed Central

    Sharma, Ajitha; Shetty, Manjunath; Parida, Amrita; Adiga, Shalini; Kamath, Shobha; Sowjanya

    2014-01-01

    Background: The effects and benefits of Acacia auriculiformis on health are not well established. This study was planned to evaluate the effect of ethanolic extract of Acacia auriculiformis leaves on learning and memory in rats. Materials and Methods: Learning and memory were evaluated using passive avoidance paradigm and rewarded alternation test (T-maze) after the oral administration of two doses (200mg/kg and 400mg/kg) of ethanolic extract of Acacia auriculiformis with rivastigmine as positive control. Forty eight rats were divided into 4 groups in each study model. Estimation of brain cholinesterase activity was done to substantiate the results of the above mentioned tests. Data was analyzed using one way Analysis of Variance (ANOVA) followed by Tukey's post-hoc test using GraphPad InStat software, version 3.06. Results: The extract produced a dose-dependent improvement in the memory score namely the step through latency in passive avoidance model (P < 0.001) and the percentage of correct responses in rewarded alternation test (P < 0.05). Dose-dependent inhibition of brain cholinesterase activity (P < 0.001) was also noted. Conclusion: The acetylcholinesterase inhibiting property of Acacia auriculiformis contributes to its memory enhancing potential. Further large scale studies are required to elucidate its benefits on cognitive function. This may offer a promising new option for the treatment of dementia and other cognitive deficits. PMID:25002806

  18. Behavioral and neurophysiological evidence that lateral paracapsular GABAergic synapses in the basolateral amygdala contribute to the acquisition and extinction of fear learning.

    PubMed

    Skelly, M J; Chappell, A M; Ariwodola, O J; Weiner, J L

    2016-01-01

    The lateral/basolateral amygdala (BLA) is crucial to the acquisition and extinction of Pavlovian fear conditioning, and synaptic plasticity in this region is considered to be a neural correlate of learned fear. We recently reported that activation of BLA β3-adrenoreceptors (β3-ARs) selectively enhances lateral paracapsular (LPC) feed-forward GABAergic inhibition onto BLA pyramidal neurons, and that intra-BLA infusion of a β3-AR agonist reduces measures of unconditioned anxiety-like behavior. Here, we utilized a combination of behavioral and electrophysiological approaches to characterize the role of BLA LPCs in the acquisition of fear and extinction learning in adult male Long-Evans rats. We report that intra-BLA microinjection of β3-AR agonists (BRL37344 or SR58611A, 1μg/0.5μL/side) prior to training fear conditioning or extinction blocks the expression of these behaviors 24h later. Furthermore,ex vivo low-frequency stimulation of the external capsule (LFS; 1Hz, 15min), which engages LPC synapses, induces LTP of BLA fEPSPs, while application of a β3-AR agonist (SR58611A, 5μM) induces LTD of fEPSPs when combined with LFS. Interestingly, fEPSP LTP is not observed in recordings from fear conditioned animals, suggesting that fear learning may engage the same mechanisms that induce synaptic plasticity at this input. In support of this, we find that LFS produces LTD of inhibitory postsynaptic currents (iLTD) at LPC GABAergic synapses, and that this effect is also absent following fear conditioning. Taken together, these data provide preliminary evidence that modulation of LPC GABAergic synapses can influence the acquisition and extinction of fear learning and related synaptic plasticity in the BLA. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Reorganization of Learning-Associated Prefrontal Synaptic Plasticity between the Recall of Recent and Remote Fear Extinction Memory

    ERIC Educational Resources Information Center

    Hugues, Sandrine; Garcia, Rene

    2007-01-01

    We have previously shown that fear extinction is accompanied by an increase of synaptic efficacy in inputs from the ventral hippocampus (vHPC) and mediodorsal thalamus (MD) to the medial prefrontal cortex (mPFC) and that disrupting these changes to mPFC synaptic transmission compromises extinction processes. The aim of this study was to examine…

  20. Reorganization of Learning-Associated Prefrontal Synaptic Plasticity between the Recall of Recent and Remote Fear Extinction Memory

    ERIC Educational Resources Information Center

    Hugues, Sandrine; Garcia, Rene

    2007-01-01

    We have previously shown that fear extinction is accompanied by an increase of synaptic efficacy in inputs from the ventral hippocampus (vHPC) and mediodorsal thalamus (MD) to the medial prefrontal cortex (mPFC) and that disrupting these changes to mPFC synaptic transmission compromises extinction processes. The aim of this study was to examine…

  1. Biologically based neural circuit modelling for the study of fear learning and extinction

    NASA Astrophysics Data System (ADS)

    Nair, Satish S.; Paré, Denis; Vicentic, Aleksandra

    2016-11-01

    The neuronal systems that promote protective defensive behaviours have been studied extensively using Pavlovian conditioning. In this paradigm, an initially neutral-conditioned stimulus is paired with an aversive unconditioned stimulus leading the subjects to display behavioural signs of fear. Decades of research into the neural bases of this simple behavioural paradigm uncovered that the amygdala, a complex structure comprised of several interconnected nuclei, is an essential part of the neural circuits required for the acquisition, consolidation and expression of fear memory. However, emerging evidence from the confluence of electrophysiological, tract tracing, imaging, molecular, optogenetic and chemogenetic methodologies, reveals that fear learning is mediated by multiple connections between several amygdala nuclei and their distributed targets, dynamical changes in plasticity in local circuit elements as well as neuromodulatory mechanisms that promote synaptic plasticity. To uncover these complex relations and analyse multi-modal data sets acquired from these studies, we argue that biologically realistic computational modelling, in conjunction with experiments, offers an opportunity to advance our understanding of the neural circuit mechanisms of fear learning and to address how their dysfunction may lead to maladaptive fear responses in mental disorders.

  2. Facets of Pavlovian and operant extinction.

    PubMed

    Lattal, K Matthew; Lattal, Kennon A

    2012-05-01

    Research on extinction is of fundamental importance in both Pavlovian and operant approaches to the experimental analysis of learning. Although these approaches are often motivated by different empirical and theoretical questions, extinction has emerged as a research area in which common themes unite the two approaches. In this review, we focus on some common considerations in the analysis of Pavlovian and operant extinction. These include methodological challenges and interpretational issues in analyzing behavior during and after extinction. We consider the different roles that theory has played in the development of research on extinction in these preparations and conclude with some attention to applications of extinction.

  3. Nonassociative learning processes determine expression and extinction of conditioned fear in mice.

    PubMed

    Kamprath, Kornelia; Wotjak, Carsten T

    2004-01-01

    Freezing to a tone following auditory fear conditioning is commonly considered as a measure of the strength of the tone-shock association. The decrease in freezing on repeated nonreinforced tone presentation following conditioning, in turn, is attributed to the formation of an inhibitory association between tone and shock that leads to a suppression of the expression of fear. This study challenges these concepts for auditory fear conditioning in mice. We show that acquisition of conditioned fear by a few tone-shock pairings is accompanied by a nonassociative sensitization process. As a consequence, the freezing response of conditioned mice seems to be determined by both associative and nonassociative memory components. Our data suggest that the intensity of freezing as a function of footshock intensity is primarily determined by the nonassociative component, whereas the associative component is more or less categorical. We next demonstrate that the decrease in freezing on repeated nonreinforced tone presentation following conditioning shows fundamental properties of habituation. Thus, it might be regarded as a habituation-like process, which abolishes the influence of sensitization on the freezing response to the tone without affecting the expression of the associative memory component. Taken together, this study merges the dual-process theory of habituation with the concept of classical fear conditioning and demonstrates that sensitization and habituation as two nonassociative learning processes may critically determine the expression of conditioned fear in mice.

  4. The extinction properties of forest components

    NASA Technical Reports Server (NTRS)

    Karam, M. A.; Fung, A. K.; Blanchard, A. J.; Nance, C. E.

    1988-01-01

    The effect of each forest component on the extinction of electromagnetic waves is investigated by modeling the branches with finite cylinders, deciduous leaves with elliptic disks, and coniferous leaves with needles. The inner field is estimated by the field inside an infinitely long cylinder of similar properties for the branches, and by the Shifrin approximation for the leaves. For each forest component analytic expressions were derived for the extinction cross section via the forward scattering theorem and for ohmic and scattered losses. For branches, the variation of the extinction cross section obtained via the forward scattering theorem is illustrated numerically as a function of the branch radius and the imaginery part of its dielectric constant. It is compared with the measurements from a single branch. For the leaves, the forward scattering theorem gives value for the extinction cross section equal to the ohmic cross section.

  5. The type 3 adenylyl cyclase is required for novel object learning and extinction of contextual memory: role of cAMP signaling in primary cilia.

    PubMed

    Wang, Zhenshan; Phan, Trongha; Storm, Daniel R

    2011-04-13

    Although primary cilia are found on neurons throughout the brain, their physiological function remains elusive. Human ciliopathies are associated with cognition defects, and transgenic mice lacking proteins expressed in primary cilia exhibit defects in learning and memory. Recently, it was reported that mice lacking the G-protein-coupling receptor somatostatin receptor-3 (SSTR3), a protein expressed predominately in the primary cilia of neurons, have defective memory for novel object recognition and lower cAMP levels in the brain. Since SSTR3 is coupled to regulation of adenylyl cyclase, this suggests that adenylyl cyclase activity in primary cilia of CNS neurons may be critical for some forms of learning and memory. Because the type 3 adenylyl cyclase (AC3) is expressed in primary cilia of hippocampal neurons, we examined AC3(-/-) mice for several forms of learning and memory. Here, we report that AC3(-/-) mice show no short-term memory for novel objects and fail to exhibit extinction of contextual fear conditioning. They also show impaired learning and memory for temporally dissociative passive avoidance. Since AC3 is exclusively expressed in primary cilia, we conclude that cAMP signals generated within primary cilia contribute to some forms of learning and memory, including extinction of contextual fear conditioning.

  6. The Type 3 Adenylyl Cyclase is Required for Novel Object Learning and Extinction of Contextual Memory: Role of cAMP Signaling in Primary Cilia

    PubMed Central

    Wang, Zhenshan; Phan, Trongha; Storm, Daniel R.

    2011-01-01

    Although primary cilia are found on neurons throughout the brain, their physiological function remains elusive. Human ciliopathies are associated with cognition defects and transgenic mice lacking proteins expressed in primary cilia exhibit defects in learning and memory. Recently, it was reported that mice lacking the G-protein coupling receptor somatostatin receptor-3 (SSTR3), a protein expressed predominately in the primary cilia of neurons, have defective memory for novel object recognition and lower cAMP levels in the brain. Since SSTR3 is coupled to regulation of adenylyl cyclase this suggests that adenylyl cyclase activity in primary cilia of CNS neurons may be critical for some forms of learning and memory. Because the type 3 adenylyl cyclase (AC3) is expressed in primary cilia of hippocampal neurons, we examined AC3−/− mice for several forms of learning and memory. Here, we report that AC3−/− mice show no short-term memory for novel objects and fail to exhibit extinction of contextual fear conditioning. They also show impaired learning and memory for temporally dissociated passive avoidance (TDPA). Since AC3 is exclusively expressed in primary cilia we conclude that cAMP signals generated within primary cilia contribute to some forms of learning and memory including extinction of contextual fear conditioning. PMID:21490195

  7. Stress and Fear Extinction

    PubMed Central

    Maren, Stephen; Holmes, Andrew

    2016-01-01

    Stress has a critical role in the development and expression of many psychiatric disorders, and is a defining feature of posttraumatic stress disorder (PTSD). Stress also limits the efficacy of behavioral therapies aimed at limiting pathological fear, such as exposure therapy. Here we examine emerging evidence that stress impairs recovery from trauma by impairing fear extinction, a form of learning thought to underlie the suppression of trauma-related fear memories. We describe the major structural and functional abnormalities in brain regions that are particularly vulnerable to stress, including the amygdala, prefrontal cortex, and hippocampus, which may underlie stress-induced impairments in extinction. We also discuss some of the stress-induced neurochemical and molecular alterations in these brain regions that are associated with extinction deficits, and the potential for targeting these changes to prevent or reverse impaired extinction. A better understanding of the neurobiological basis of stress effects on extinction promises to yield novel approaches to improving therapeutic outcomes for PTSD and other anxiety and trauma-related disorders. PMID:26105142

  8. One-trial learning and superior resistance to extinction of autonomic responses conditioned to potentially phobic stimuli.

    PubMed

    Ohman, A; Eriksson, A; Olofsson, C

    1975-02-01

    Human subjects were exposed to pictures of potentially phobic (snakes) and supposedly neutral (houses) objects as conditioned stimuli (CSs) in a Pavlovian conditioning experiment with shock as unconditioned stimulus (US), and skin conductance and finger pulse volume as dependent variables. The skin conductance responses conditioned to phobic stimuli were acquired after one CS-US pairing, and showed practically no extinction, whereas the responses to neutral stimuli showed very little resistance to extinction after both 1 and 5 reinforcements. The superior resistance to extinction of the phobic condition was interpreted to be a specific associative effect. In general, the skin conductance acquisition data showed tendencies similar to those during extinction. For finger pulse volume responses, however, there were very weak conditioning effects, and no effect of stimulus.

  9. Extinctions of life

    NASA Technical Reports Server (NTRS)

    Sepkoski, J. J. Jr; Sepkoski JJ, J. r. (Principal Investigator)

    1988-01-01

    This meeting presentation examines mass extinctions through earth's history. Extinctions are charted for marine families and marine genera. Timing of marine genera extinctions is discussed. Periodicity in extinctions during the Mesozoic and Cenozoic eras is plotted and compared with Paleozoic extinction peaks. The role of extinction in evolution and mankind's role in present extinctions are examined.

  10. Stress during puberty boosts metabolic activation associated with fear-extinction learning in hippocampus, basal amygdala and cingulate cortex.

    PubMed

    Toledo-Rodriguez, Maria; Pitiot, Alain; Paus, Tomáš; Sandi, Carmen

    2012-07-01

    Adolescence is characterized by major developmental changes that may render the individual vulnerable to stress and the development of psychopathologies in a sex-specific manner. Earlier we reported lower anxiety-like behavior and higher risk-taking and novelty seeking in rats previously exposed to peri-pubertal stress. Here we studied whether peri-pubertal stress affected the acquisition and extinction of fear memories and/or the associated functional engagement of various brain regions, as assessed with 2-deoxyglucose. We showed that while peri-pubertal stress reduced freezing during the acquisition of fear memories (training) in both sexes, it had a sex-specific effect on extinction of these memories. Moreover hippocampus, basal amygdala and cingulate and motor cortices showed higher metabolic rates during extinction in rats exposed to peri-pubertal stress. Interestingly, activation of the infralimbic cortex was negatively correlated with freezing during extinction only in control males, while only males stressed during puberty showed a significant correlation between behavior during extinction and metabolic activation of hippocampus, amygdala and paraventricular nucleus. No correlations between brain activation and behavior during extinction were observed in females (control or stress). These results indicate that exposure to peri-pubertal stress affects behavior and brain metabolism when the individual is exposed to an additional stressful challenge. Some of these effects are sex-specific.

  11. The roles of the nucleus accumbens core, dorsomedial striatum, and dorsolateral striatum in learning: performance and extinction of Pavlovian fear-conditioned responses and instrumental avoidance responses.

    PubMed

    Wendler, Etieli; Gaspar, Jessica C C; Ferreira, Tatiana L; Barbiero, Janaína K; Andreatini, Roberto; Vital, Maria A B F; Blaha, Charles D; Winn, Philip; Da Cunha, Claudio

    2014-03-01

    This study examined the effects of bilateral excitotoxic lesions of the nucleus accumbens core (NAc-co), dorsomedial striatum (DMS) or dorsolateral striatum (DLS) of rats on the learning and extinction of Pavlovian and instrumental components of conditioned avoidance responses (CARs). None of the lesions caused sensorimotor deficits that could affect locomotion. Lesions of the NAc-co, but not DMS or DLS, decreased unconditioned and conditioned freezing. The NAc-co and DLS lesioned rats learned the 2-way active avoidance task more slowly. These results suggest: (i) CARs depend on both Pavlovian and instrumental learning; (ii) learning the Pavlovian component of CARs depends on the NAc-co; learning the instrumental component of CARs depends on the DLS, NAc and DMS; (iii) although the NAc-co is also needed for learning the instrumental component, it is not clear whether it plays a role in learning the instrumental component per se or if it simply allows learning of the Pavlovian component which is a pre-condition for learning the instrumental component; (iv) we did not find evidence that the DMS and DLS play the same roles in habit and goal-directed aspects of the instrumental component of CARs as observed in appetitive motivated instrumental responding.

  12. Australian Extinctions

    ERIC Educational Resources Information Center

    Science Teacher, 2005

    2005-01-01

    Massive extinctions of animals and the arrival of the first humans in ancient Australia--which occurred 45,000 to 55,000 years ago--may be linked. Researchers at the Carnegie Institution, University of Colorado, Australian National University, and Bates College believe that massive fires set by the first humans may have altered the ecosystem of…

  13. Australian Extinctions

    ERIC Educational Resources Information Center

    Science Teacher, 2005

    2005-01-01

    Massive extinctions of animals and the arrival of the first humans in ancient Australia--which occurred 45,000 to 55,000 years ago--may be linked. Researchers at the Carnegie Institution, University of Colorado, Australian National University, and Bates College believe that massive fires set by the first humans may have altered the ecosystem of…

  14. An Analysis of Paid Family and Sick Leave Advocacy in Louisiana: Lessons Learned.

    PubMed

    Raabe, Phyllis Hutton; Theall, Katherine P

    2016-01-01

    In contrast with other developed countries, the United States lacks national paid maternity/family and sick leave policies, negatively impacting the health and economic security of both female and male workers and their children. Employer paid family and sick leave policies cover only about half of workers, and those lacking paid leaves are more likely to be less educated and with lower incomes. Louisiana has high proportions of poor and low income workers who especially would benefit from national or state paid leave policies. In the absence of national paid leaves, several states and cities have implemented paid family and sick leaves. In this context and following the American Public Health Association's endorsement of paid family and sick leaves for health and wellbeing, the Tulane University Mary Amelia Women's Center decided to advocate for paid leave policies in Louisiana. Highlights of a Louisiana spring 2015 initiative were a talk by the President of the Institute for Women's Policy Research on the economic and health benefits of paid family and sick leaves and bills submitted by a State Senator. As has happened elsewhere, opposition from businesses and Republican legislators blocked passage. This outcome fit the Center's original expectations that communicating about the important health and other benefits of paid family and sick leaves, and developing support for state-wide policies, would be a long process-but one important to begin. The initiative in Louisiana may provide insights for paid leave advocacy elsewhere. Copyright © 2016 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.

  15. Extinction of Contextual Fear with Timed Exposure to Enriched Environment: A Differential Effect

    PubMed Central

    Hegde, Preethi; O'Mara, Shane; Laxmi, Thenkanidiyoor Rao

    2017-01-01

    Background Extinction of fear memory depends on the environmental and emotional cues. Furthermore, consolidation of extinction is also dependent on the environmental exposure. But, the relationship of the time of the exposure to a variety of environmental cues is not well known. The important region involved in facilitation of extinction of fear memory is through diversion of the flow of information leaving the lateral nucleus of amygdala. Purpose The study aimed to address a question to explain how these brain regions react to environmental stimulation during the retention and extinction of fear memory. Methods An enriched environment (EE) is assumed to mediate extinction of fear memory, we examined the apparent discrepancy between the effects of defensive response, the freezing behavior induced by Pavlovian classical fear conditioning by subjecting them to variance in the timing to EE. The different timing of EE exposure was 10 days of EE either before fear conditioning and/or after extinction training to the rats. The local field potentials was recorded from CA1 hippocampus, lateral nucleus of amygdala and infralimbic region of medial prefrontal cortex (mPFC) during the fear learning and extinction from the control rats and rats exposed to EE before and after fear conditioning. Results Exposure to EE before the fear conditioning and after extinction training was more effective in the extinction fear memory. In addition, we also found switching from exploratory locomotion to freezing during retention of contextual fear memory which was associated with decreased theta power and reduced synchronized theta oscillations in CA1-hippocampus, lateral nucleus of amygdala, and infralimbic region of mPFC. Conclusion Thus, we propose that the timing of exposure to EE play a key role in the extinction of fear memory. PMID:28588364

  16. Caring and Learning Together: Exploring the Relationship between Parental Leave and Early Childhood Education and Care

    ERIC Educational Resources Information Center

    Moss, Peter

    2012-01-01

    Parental leave and early childhood education and care (ECEC) are two policies widely proposed and implemented to support working parents with young children. This article examines entitlement to leave and ECEC in 25 European countries, including 22 EU Member and Accession States, and the relationship between them, in particular to what degree…

  17. Caring and Learning Together: Exploring the Relationship between Parental Leave and Early Childhood Education and Care

    ERIC Educational Resources Information Center

    Moss, Peter

    2012-01-01

    Parental leave and early childhood education and care (ECEC) are two policies widely proposed and implemented to support working parents with young children. This article examines entitlement to leave and ECEC in 25 European countries, including 22 EU Member and Accession States, and the relationship between them, in particular to what degree…

  18. Context and Behavioral Processes in Extinction

    ERIC Educational Resources Information Center

    Bouton, Mark E.

    2004-01-01

    This article provides a selective review and integration of the behavioral literature on Pavlovian extinction. The first part reviews evidence that extinction does not destroy the original learning, but instead generates new learning that is especially context-dependent. The second part examines insights provided by research on several related…

  19. Context and Behavioral Processes in Extinction

    ERIC Educational Resources Information Center

    Bouton, Mark E.

    2004-01-01

    This article provides a selective review and integration of the behavioral literature on Pavlovian extinction. The first part reviews evidence that extinction does not destroy the original learning, but instead generates new learning that is especially context-dependent. The second part examines insights provided by research on several related…

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

    ERIC Educational Resources Information Center

    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…

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

    ERIC Educational Resources Information Center

    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…

  2. Electromagnetic wave extinction within a forested canopy

    NASA Technical Reports Server (NTRS)

    Karam, M. A.; Fung, A. K.

    1989-01-01

    A forested canopy is modeled by a collection of randomly oriented finite-length cylinders shaded by randomly oriented and distributed disk- or needle-shaped leaves. For a plane wave exciting the forested canopy, the extinction coefficient is formulated in terms of the extinction cross sections (ECSs) in the local frame of each forest component and the Eulerian angles of orientation (used to describe the orientation of each component). The ECSs in the local frame for the finite-length cylinders used to model the branches are obtained by using the forward-scattering theorem. ECSs in the local frame for the disk- and needle-shaped leaves are obtained by the summation of the absorption and scattering cross-sections. The behavior of the extinction coefficients with the incidence angle is investigated numerically for both deciduous and coniferous forest. The dependencies of the extinction coefficients on the orientation of the leaves are illustrated numerically.

  3. Electromagnetic wave extinction within a forested canopy

    NASA Technical Reports Server (NTRS)

    Karam, M. A.; Fung, A. K.

    1989-01-01

    A forested canopy is modeled by a collection of randomly oriented finite-length cylinders shaded by randomly oriented and distributed disk- or needle-shaped leaves. For a plane wave exciting the forested canopy, the extinction coefficient is formulated in terms of the extinction cross sections (ECSs) in the local frame of each forest component and the Eulerian angles of orientation (used to describe the orientation of each component). The ECSs in the local frame for the finite-length cylinders used to model the branches are obtained by using the forward-scattering theorem. ECSs in the local frame for the disk- and needle-shaped leaves are obtained by the summation of the absorption and scattering cross-sections. The behavior of the extinction coefficients with the incidence angle is investigated numerically for both deciduous and coniferous forest. The dependencies of the extinction coefficients on the orientation of the leaves are illustrated numerically.

  4. Psychological and neural mechanisms of experimental extinction: a selective review.

    PubMed

    Delamater, Andrew R; Westbrook, R Frederick

    2014-02-01

    The present review examines key psychological concepts in the study of experimental extinction and implications these have for an understanding of the underlying neurobiology of extinction learning. We suggest that many of the signature characteristics of extinction learning (spontaneous recovery, renewal, reinstatement, rapid reacquisition) can be accommodated by the standard associative learning theory assumption that extinction results in partial erasure of the original learning together with new inhibitory learning. Moreover, we consider recent behavioral and neural evidence that supports the partial erasure view of extinction, but also note shortcomings in our understanding of extinction circuits as these relate to the negative prediction error concept. Recent work suggests that common prediction error and stimulus-specific prediction error terms both may be required to explain neural plasticity both in acquisition and extinction learning. In addition, we suggest that many issues in the content of extinction learning have not been fully addressed in current research, but that neurobiological approaches should be especially helpful in addressing such issues. These include questions about the nature of extinction learning (excitatory CS-No US, inhibitory CS-US learning, occasion setting processes), especially as this relates to studies of the micro-circuitry of extinction, as well as its representational content (sensory, motivational, response). An additional understudied problem in extinction research is the role played by attention processes and their underlying neural networks, although some research and theory converge on the idea that extinction is accompanied by attention decrements (i.e., habituation-like processes).

  5. Psychological and Neural Mechanisms of Experimental Extinction: A Selective Review

    PubMed Central

    Delamater, Andrew R.; Westbrook, R. Frederick

    2013-01-01

    The present review examines key psychological concepts in the study of experimental extinction and implications these have for an understanding of the underlying neurobiology of extinction learning. We suggest that many of the signature characteristics of extinction learning (spontaneous recovery, renewal, reinstatement, rapid reacquisition) can be accommodated by the standard associative learning theory assumption that extinction results in partial erasure of the original learning together with new inhibitory learning. Moreover, we consider recent behavioral and neural evidence that supports the partial erasure view of extinction, but also note shortcomings in our understanding of extinction circuits as these relate to the negative prediction error concept. Recent work suggests that common prediction error and stimulus-specific prediction error terms both may be required to explain neural plasticity both in acquisition and extinction learning. In addition, we suggest that many issues in the content of extinction learning have not been fully addressed in current research, but that neurobiological approaches should be especially helpful in addressing such issues. These include questions about the nature of extinction learning (excitatory CS-No US, inhibitory CS-US learning, occasion setting processes), especially as this relates to studies of the micro-circuitry of extinction, as well as its representational content (sensory, motivational, response). An additional understudied problem in extinction research is the role played by attention processes and their underlying neural networks, although some research and theory converge on the idea that extinction is accompanied by attention decrements (i.e., habituation-like processes). PMID:24104049

  6. Leaving School — learning at SEA: Regular high school education alongside polar research

    NASA Astrophysics Data System (ADS)

    Gatti, Susanne

    2010-05-01

    Against the background of unsatisfactory results from the international OECD study PISA (Program for International Student Assessment), Germany is facing a period of intense school reforms. Looking back at a tradition of school culture with too few changes during the last century, quick and radical renewal of the school system is rather unlikely. Furthermore students are increasingly turning away from natural sciences [1]. The AWI aims at providing impulses for major changes in the schooling system and is offering solid science education not only for university students but also for a larger audience. All efforts towards this goal are interconnected within the project SEA (Science & Education @ the AWI). With the school-term of 2002/03 the Alfred-Wegener-Institute for Polar and Marine Research started HIGHSEA (High school of SEA). The program is the most important component of SEA. Each year 22 high school students (grade 10 or 11) are admitted to HIGHSEA spending their last three years of school not at school but at the institute. Four subjects (biology as a major, chemistry, math and English as accessory subjects) are combined and taught fully integrated. Students leave their school for two days each week to study, work and explore all necessary topics at the AWI. All of the curricular necessities of the four subjects have been rearranged in their temporal sequencing thus enabling a conceptual formulation of four major questions to be dealt with in the course of the three-year program [2]. Students are taught by teachers of the cooperation schools as well as by scientists of the AWI. Close links and intense cooperation between both groups are the basis of fundamental changes in teaching and learning climate. We are organizing expeditions for every group of HIGHSEA-students (e. g. to the Arctic or to mid-Atlantic seamounts). For each student expedition we devise a "real" research question. Usually a single working group at the AWI has a special interest in the

  7. Impossible Extinction

    NASA Astrophysics Data System (ADS)

    Cockell, Charles S.

    2003-03-01

    Every 225 million years the Earth, and all the life on it, completes one revolution around the Milky Way Galaxy. During this remarkable journey, life is influenced by calamitous changes. Comets and asteroids strike the surface of the Earth, stars explode, enormous volcanoes erupt, and, more recently, humans litter the planet with waste. Many animals and plants become extinct during the voyage, but humble microbes, simple creatures made of a single cell, survive this journey. This book takes a tour of the microbial world, from the coldest and deepest places on Earth to the hottest and highest, and witnesses some of the most catastrophic events that life can face. Impossible Extinction tells this remarkable story to the general reader by explaining how microbes have survived on Earth for over three billion years. Charles Cockell received his doctorate from the University of Oxford, and is currently a microbiologist with rhe Search for Extraterrestrial Intelligence Institute (SETI), based at the British Antarctic Survey in Cambridge, UK. His research focusses on astrobiology, life in the extremes and the human exploration of Mars. Cockell has been on expeditions to the Arctic, Antarctic, Mongolia, and in 1993 he piloted a modified insect-collecting ultra-light aircraft over the Indonesian rainforests. He is Chair of the Twenty-one Eleven Foundation for Exploration, a charity that supports expeditions that forge links between space exploration and environmentalism.

  8. Interstellar Extinction

    NASA Astrophysics Data System (ADS)

    Gontcharov, G. A.

    2016-12-01

    This review describes our current understanding of interstellar extinction. This differ substantially from the ideas of the 20th century. With infrared surveys of hundreds of millions of stars over the entire sky, such as 2MASS, SPITZER-IRAC, and WISE, we have looked at the densest and most rarefied regions of the interstellar medium at distances of a few kpc from the Sun. Observations at infrared and microwave wavelengths, where the bulk of the interstellar dust absorbs and radiates, have brought us closer to an understanding of the distribution of the dust particles on scales of the Galaxy and the universe. We are in the midst of a scientific revolution in our understanding of the interstellar medium and dust. Progress in, and the key results of, this revolution are still difficult to predict. Nevertheless, (a) a physically justified model has been developed for the spatial distribution of absorbing material over the nearest few kiloparsecs, including the Gould belt as a dust container, which gives an accurate estimate of the extinction for any object just by its galactic coordinates. It is also clear that (b) the interstellar medium contains roughly half the mass of matter in the galactic vicinity of the solar system (the other half is made up of stars, their remnants, and dark matter) and (c) the interstellar medium and, especially, dust, differ substantially in different regions of space and deep space cannot be understood by only studying near space.

  9. In the Laboratory and during Free-Flight: Old Honey Bees Reveal Learning and Extinction Deficits that Mirror Mammalian Functional Decline

    PubMed Central

    Münch, Daniel; Baker, Nicholas; Kreibich, Claus D.; Bråten, Anders T.; Amdam, Gro V.

    2010-01-01

    Loss of brain function is one of the most negative and feared aspects of aging. Studies of invertebrates have taught us much about the physiology of aging and how this progression may be slowed. Yet, how aging affects complex brain functions, e.g., the ability to acquire new memory when previous experience is no longer valid, is an almost exclusive question of studies in humans and mammalian models. In these systems, age related cognitive disorders are assessed through composite paradigms that test different performance tasks in the same individual. Such studies could demonstrate that afflicted individuals show the loss of several and often-diverse memory faculties, and that performance usually varies more between aged individuals, as compared to conspecifics from younger groups. No comparable composite surveying approaches are established yet for invertebrate models in aging research. Here we test whether an insect can share patterns of decline similar to those that are commonly observed during mammalian brain aging. Using honey bees, we combine restrained learning with free-flight assays. We demonstrate that reduced olfactory learning performance correlates with a reduced ability to extinguish the spatial memory of an abandoned nest location (spatial memory extinction). Adding to this, we show that learning performance is more variable in old honey bees. Taken together, our findings point to generic features of brain aging and provide the prerequisites to model individual aspects of learning dysfunction with insect models. PMID:20976061

  10. Exposure to a fearful context during periods of memory plasticity impairs extinction via hyperactivation of frontal-amygdalar circuits.

    PubMed

    Stafford, James M; Maughan, DeeAnna K; Ilioi, Elena C; Lattal, K Matthew

    2013-02-19

    An issue of increasing theoretical and translational importance is to understand the conditions under which learned fear can be suppressed, or even eliminated. Basic research has pointed to extinction, in which an organism is exposed to a fearful stimulus (such as a context) in the absence of an expected aversive outcome (such as a shock). This extinction process results in the suppression of fear responses, but is generally thought to leave the original fearful memory intact. Here, we investigate the effects of extinction during periods of memory lability on behavioral responses and on expression of the immediate-early gene c-Fos within fear conditioning and extinction circuits. Our results show that long-term extinction is impaired when it occurs during time periods during which the memory should be most vulnerable to disruption (soon after conditioning or retrieval). These behavioral effects are correlated with hyperactivation of medial prefrontal cortex and amygdala subregions associated with fear expression rather than fear extinction. These findings demonstrate that behavioral experiences during periods of heightened fear prevent extinction and prolong the conditioned fear response.

  11. Exposure to a fearful context during periods of memory plasticity impairs extinction via hyperactivation of frontal-amygdalar circuits

    PubMed Central

    Stafford, James M.; Maughan, DeeAnna K.; Ilioi, Elena C.; Lattal, K. Matthew

    2013-01-01

    An issue of increasing theoretical and translational importance is to understand the conditions under which learned fear can be suppressed, or even eliminated. Basic research has pointed to extinction, in which an organism is exposed to a fearful stimulus (such as a context) in the absence of an expected aversive outcome (such as a shock). This extinction process results in the suppression of fear responses, but is generally thought to leave the original fearful memory intact. Here, we investigate the effects of extinction during periods of memory lability on behavioral responses and on expression of the immediate–early gene c-Fos within fear conditioning and extinction circuits. Our results show that long-term extinction is impaired when it occurs during time periods during which the memory should be most vulnerable to disruption (soon after conditioning or retrieval). These behavioral effects are correlated with hyperactivation of medial prefrontal cortex and amygdala subregions associated with fear expression rather than fear extinction. These findings demonstrate that behavioral experiences during periods of heightened fear prevent extinction and prolong the conditioned fear response. PMID:23422280

  12. Experimental extinction in Pavlovian conditioning: behavioural and neuroscience perspectives.

    PubMed

    Delamater, Andrew R

    2004-04-01

    This paper reviews the behavioural and neuroscience literatures on extinction in Pavlovian conditioning with a view towards finding possible points of contact between these two often independent lines of investigation. Recent discoveries at the behavioural level indicate (1) that conditioned stimulus (CS)-unconditioned stimulus (US) associations specific in their sensory content are fully preserved during extinction, (2) that inhibitory stimulus-response associations appear to be learned during extinction, (3) that extinction is influenced by the level of activation of the US representation during nonreinforced trials, (4) that decreases in attention can influence conditioned performance during extinction, and (5) that contexts acquire an ability to modulate learning during both conditioning and extinction. Recent discoveries at the neural systems level suggest (1) that the hippocampus is important in context-specific learning during extinction, (2) that the prefrontal cortex is possibly important in long-term memory for extinction, (3) that the basolateral amygdala may be important in sustaining attention to a CS during extinction, (4) that NMDA receptors are important either in neural plasticity during extinction or by affecting the value of the US representation during extinction, and (5) that the GABAergic system may partially mediate inhibitory learning during extinction. It is concluded that both of these levels of analysis can benefit the other in the pursuit of a more comprehensive understanding of extinction.

  13. Learning to Leave Liberalism...And Live with Complicity, Conundrum and Moral Chagrin

    ERIC Educational Resources Information Center

    Boyd, Dwight

    2011-01-01

    This paper is a story of personal learning. I locate its beginning in my early, comfortable adoption of liberalism as the preferred perspective for my work as a philosopher of education. I then trace how and why I became disaffected with this perspective. I describe how learning from students, feminism and critical race theory led to an acceptance…

  14. Learning to Leave Liberalism...And Live with Complicity, Conundrum and Moral Chagrin

    ERIC Educational Resources Information Center

    Boyd, Dwight

    2011-01-01

    This paper is a story of personal learning. I locate its beginning in my early, comfortable adoption of liberalism as the preferred perspective for my work as a philosopher of education. I then trace how and why I became disaffected with this perspective. I describe how learning from students, feminism and critical race theory led to an acceptance…

  15. Cannabinoid facilitation of fear extinction memory recall in humans

    PubMed Central

    Rabinak, Christine A.; Angstadt, Mike; Sripada, Chandra S.; Abelson, James L.; 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 the cannabinoid system during extinction learning enhances fear extinction and its retention. Specifically, CB1 receptor agonists, such as Δ9-tetrahydrocannibinol (THC), can facilitate extinction recall by preventing recovery of extinguished fear in rats. However, this phenomenon has not been investigated in humans. We conducted a study using a randomized, double-blind, placebo-controlled, between-subjects design, coupling a standard Pavlovian fear extinction paradigm and simultaneous skin conductance response (SCR) recording with an acute pharmacological challenge with oral dronabinol (synthetic THC) or placebo (PBO) 2 hours prior to extinction learning in 29 healthy adult volunteers (THC = 14; PBO = 15) and tested extinction retention 24 hours after extinction learning. Compared to subjects that received PBO, subjects that received THC showed low SCR to a previously extinguished CS when extinction memory recall was tested 24 hours after extinction learning, suggesting that THC prevented the recovery of fear. These results provide the first evidence that pharmacological enhancement of extinction learning is feasible in humans using cannabinoid system modulators, which may thus warrant further development and clinical testing. PMID:22796109

  16. Outcome-Specific Transfer between Predictive and Instrumental Learning Is Unaffected by Extinction but Reversed by Counterconditioning in Human Participants

    ERIC Educational Resources Information Center

    Rosas, Juan M.; Paredes-Olay, Maria C.; Garcia-Gutierrez, Ana; Espinosa, Juan J.; Abad, Maria J. F.

    2010-01-01

    Three experiments were conducted to explore the effects of different interference treatments upon outcome-specific transfer from predictive learning to instrumental responding. A computer game was designed in which participants had to defend Andalusia from navy and air-force attacks. Participants learned the relationship between two instrumental…

  17. Outcome-Specific Transfer between Predictive and Instrumental Learning Is Unaffected by Extinction but Reversed by Counterconditioning in Human Participants

    ERIC Educational Resources Information Center

    Rosas, Juan M.; Paredes-Olay, Maria C.; Garcia-Gutierrez, Ana; Espinosa, Juan J.; Abad, Maria J. F.

    2010-01-01

    Three experiments were conducted to explore the effects of different interference treatments upon outcome-specific transfer from predictive learning to instrumental responding. A computer game was designed in which participants had to defend Andalusia from navy and air-force attacks. Participants learned the relationship between two instrumental…

  18. Fibroblast Growth Factor-2 Alters the Nature of Extinction

    ERIC Educational Resources Information Center

    Graham, Bronwyn M.; Richardson, Rick

    2011-01-01

    These experiments examined the effects of the NMDA-receptor (NMDAr) antagonist MK801 on reacquisition and re-extinction of a conditioned fear that had been previously extinguished before injection of fibroblast growth factor-2 (FGF2) or vehicle. Recent findings have shown that relearning and re-extinction, unlike initial learning and extinction,…

  19. Fibroblast Growth Factor-2 Alters the Nature of Extinction

    ERIC Educational Resources Information Center

    Graham, Bronwyn M.; Richardson, Rick

    2011-01-01

    These experiments examined the effects of the NMDA-receptor (NMDAr) antagonist MK801 on reacquisition and re-extinction of a conditioned fear that had been previously extinguished before injection of fibroblast growth factor-2 (FGF2) or vehicle. Recent findings have shown that relearning and re-extinction, unlike initial learning and extinction,…

  20. Can Transcranial Direct Current Stimulation Augment Extinction of Conditioned Fear?

    PubMed Central

    van ’t Wout, Mascha; Mariano, Timothy Y.; Garnaat, Sarah L.; Reddy, Madhavi K.; Rasmussen, Steven A.; Greenberg, Benjamin D.

    2016-01-01

    Background Exposure-based therapy parallels extinction learning of conditioned fear. Prior research points to the ventromedial prefrontal cortex as a potential site for the consolidation of extinction learning and subsequent retention of extinction memory. Objective/hypothesis The present study aimed to evaluate whether the application of non-invasive transcranial direct current stimulation (tDCS) during extinction learning enhances late extinction and early recall in human participants. Methods Forty-four healthy volunteers completed a 2-day Pavlovian fear conditioning, extinction, and recall paradigm while skin conductance activity was continuously measured. Twenty-six participants received 2 mA anodal tDCS over EEG coordinate AF3 during extinction of a first conditioned stimulus. The remaining 18 participants received similar tDCS during extinction of a second conditioned stimulus. Sham stimulation was applied for the balance of extinction trials in both groups. Normalized skin conductance changes were analyzed using linear mixed models to evaluate effects of tDCS over late extinction and early recall trials. Results We observed a significant interaction between timing of tDCS during extinction blocks and changes in skin conductance reactivity over late extinction trials. These data indicate that tDCS was associated with accelerated late extinction learning of a second conditioned stimulus after tDCS was combined with extinction learning of a previous conditioned stimulus. No significant effects of tDCS timing were observed on early extinction recall. Conclusions Results could be explained by an anxiolytic aftereffect of tDCS and extend previous studies on tDCS-induced modulation of fear and threat related learning processes. These findings support further exploration of the clinical use of tDCS. PMID:27037186

  1. Can Transcranial Direct Current Stimulation Augment Extinction of Conditioned Fear?

    PubMed

    van 't Wout, Mascha; Mariano, Timothy Y; Garnaat, Sarah L; Reddy, Madhavi K; Rasmussen, Steven A; Greenberg, Benjamin D

    2016-01-01

    Exposure-based therapy parallels extinction learning of conditioned fear. Prior research points to the ventromedial prefrontal cortex as a potential site for the consolidation of extinction learning and subsequent retention of extinction memory. The present study aimed to evaluate whether the application of non-invasive transcranial direct current stimulation (tDCS) during extinction learning enhances late extinction and early recall in human participants. Forty-four healthy volunteers completed a 2-day Pavlovian fear conditioning, extinction, and recall paradigm while skin conductance activity was continuously measured. Twenty-six participants received 2 mA anodal tDCS over EEG coordinate AF3 during extinction of a first conditioned stimulus. The remaining 18 participants received similar tDCS during extinction of a second conditioned stimulus. Sham stimulation was applied for the balance of extinction trials in both groups. Normalized skin conductance changes were analyzed using linear mixed models to evaluate effects of tDCS over late extinction and early recall trials. We observed a significant interaction between timing of tDCS during extinction blocks and changes in skin conductance reactivity over late extinction trials. These data indicate that tDCS was associated with accelerated late extinction learning of a second conditioned stimulus after tDCS was combined with extinction learning of a previous conditioned stimulus. No significant effects of tDCS timing were observed on early extinction recall. Results could be explained by an anxiolytic aftereffect of tDCS and extend previous studies on tDCS-induced modulation of fear and threat related learning processes. These findings support further exploration of the clinical use of tDCS. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. The extinction context enables extinction performance after a change in context

    PubMed Central

    Nelson, James Byron; Gregory, Pamela; Sanjuan, Maria del Carmen

    2012-01-01

    One experiment with human participants determined the extent to which recovery of extinguished responding with a context switch was due to a failure to retrieve contextually-controlled learning, or some other process such as participants learning that context changes signal reversals in the meaning of stimulus – outcome relationships. In a video game, participants learned to suppress mouse clicking in the presence of a stimulus that predicted an attack. Then, that stimulus underwent extinction in a different context (environment within the game). Following extinction, suppression was recovered and then extinguished again during testing in the conditioning context. In a final test, participants that were tested in the context where extinction first took place showed less of a recovery than those tested in a neutral context, but they showed a recovery of suppression nevertheless. A change in context tended to cause a change in the meaning of the stimulus, leading to recovery in both the neutral and extinction contexts. The extinction context attenuated that recovery, perhaps by enabling retrieval of the learning that took place in extinction. Recovery outside an extinction context is due to a failure of the context to enable the learning acquired during extinction, but only in part. PMID:22521549

  3. Reinforcer devaluation by extinction depends on the food restriction protocol.

    PubMed

    Baker, Tyson W; Weisman, Ronald G; Beninger, Richard J

    2012-05-01

    A common feature of reinforcer devaluation studies is that new learning induces the devaluation. The present study used extinction to induce new learning about the conditioned reinforcer in a heterogeneous chain schedule. Rats pressed a lever in a heterogeneous chain schedule to produce a conditioned reinforcer (light) associated with the opportunity to obtain an unconditioned reinforcer (food) by pulling a chain. The density of food reinforcement correlated with the conditioned reinforcer was varied in a comparison of continuous and variable-ratio reinforcement schedules of chain pulling; this had no noticeable effect on conditioned reinforcer devaluation produced by extinction of chain pulling. In contrast, how rats were deprived appeared to matter very much. Restricting meal duration to 1h daily produced more lever pressing during baseline training and a greater reductive effect of devaluation on lever pressing than restricting body weight to 80% of a control rat's weight, which eliminated the devaluation effect. Further analysis suggested that meal-duration restriction may have produced devaluation effects because it was more effective than weight restriction in reducing rats' body weights. Our results exposed an important limitation on the devaluation of conditioned reinforcers: slight differences in food restriction, using two commonly employed food-restriction procedures, can produce completely different interpretations of reinforcer devaluation while leaving reinforcer-based learning intact.

  4. Water, Weeds and Autumn Leaves: Learning to Be Drier in the Alpine Region

    ERIC Educational Resources Information Center

    Foley, Annette; Grace, Lauri

    2009-01-01

    Our paper explores how and what adults living and working in the Alpine region of Victoria understand and are learning about the changes to water availability, in a time when the response to water availability is subject to extensive debate and policy attention. Interviews for this study were conducted in the towns of Bright and Mount Beauty, with…

  5. Dual role of serotonin in the acquisition and extinction of reward-driven learning: involvement of 5-HT1A, 5-HT2A and 5-HT3 receptors.

    PubMed

    Frick, Luciana Romina; Bernardez-Vidal, Micaela; Hocht, Christian; Zanutto, Bonifacio Silvano; Rapanelli, Maximiliano

    2015-01-15

    Serotonin (5-HT) has been proposed as a possible encoder of reward. Nevertheless, the role of this neurotransmitter in reward-based tasks is not well understood. Given that the major serotonergic circuit in the rat brain comprises the dorsal raphe nuclei and the medial prefrontal cortex (mPFC), and because the latter structure is involved in the control of complex behaviors and expresses 1A (5-HT1A), 2A (5-HT2A), and 3 (5-HT3) receptors, the aim was to study the role of 5-HT and of these receptors in the acquisition and extinction of a reward-dependent operant conditioning task. Long Evans rats were trained in an operant conditioning task while receiving fluoxetine (serotonin reuptake inhibitor, 10mg/kg), tianeptine (serotonin reuptake enhancer, 10mg/kg), buspirone (5-HT1A partial agonist, 10mg/kg), risperidone (5-HT2A antagonist, 1mg/kg), ondansetron (5-HT3 antagonist, 2mg/kg) or vehicle. Then, animals that acquired the operant conditioning without any treatment were trained to extinct the task in the presence of the pharmacological agents. Fluoxetine impaired acquisition but improved extinction. Tianeptine administration induced the opposite effects. Buspirone induced a mild deficit in acquisition and had no effects during the extinction phase. Risperidone administration resulted in learning deficits during the acquisition phase, although it promoted improved extinction. Ondansetron treatment showed a deleterious effect in the acquisition phase and an overall improvement in the extinction phase. These data showed a differential role of 5-HT in the acquisition and extinction of an operant conditioning task, suggesting that it may have a dual function in reward encoding.

  6. Context and behavioral processes in extinction.

    PubMed

    Bouton, Mark E

    2004-01-01

    This article provides a selective review and integration of the behavioral literature on Pavlovian extinction. The first part reviews evidence that extinction does not destroy the original learning, but instead generates new learning that is especially context-dependent. The second part examines insights provided by research on several related behavioral phenomena (the interference paradigms, conditioned inhibition, and inhibition despite reinforcement). The final part examines four potential causes of extinction: the discrimination of a new reinforcement rate, generalization decrement, response inhibition, and violation of a reinforcer expectation. The data are consistent with behavioral models that emphasize the role of generalization decrement and expectation violation, but would be more so if those models were expanded to better accommodate the finding that extinction involves a context-modulated form of inhibitory learning.

  7. An Efficient Leave-One-Out Cross-Validation-Based Extreme Learning Machine (ELOO-ELM) With Minimal User Intervention.

    PubMed

    Shao, Zhifei; Er, Meng Joo; Wang, Ning

    2016-08-01

    It is well known that the architecture of the extreme learning machine (ELM) significantly affects its performance and how to determine a suitable set of hidden neurons is recognized as a key issue to some extent. The leave-one-out cross-validation (LOO-CV) is usually used to select a model with good generalization performance among potential candidates. The primary reason for using the LOO-CV is that it is unbiased and reliable as long as similar distribution exists in the training and testing data. However, the LOO-CV has rarely been implemented in practice because of its notorious slow execution speed. In this paper, an efficient LOO-CV formula and an efficient LOO-CV-based ELM (ELOO-ELM) algorithm are proposed. The proposed ELOO-ELM algorithm can achieve fast learning speed similar to the original ELM without compromising the reliability feature of the LOO-CV. Furthermore, minimal user intervention is required for the ELOO-ELM, thus it can be easily adopted by nonexperts and implemented in automation processes. Experimentation studies on benchmark datasets demonstrate that the proposed ELOO-ELM algorithm can achieve good generalization with limited user intervention while retaining the efficiency feature.

  8. Serotonergic antidepressants decrease hedonic signals but leave learning signals in the nucleus accumbens unaffected.

    PubMed

    Graf, Heiko; Metzger, Coraline D; Walter, Martin; Abler, Birgit

    2016-01-06

    Investigating the effects of serotonergic antidepressants on neural correlates of visual erotic stimulation revealed decreased reactivity within the dopaminergic reward network along with decreased subjective sexual functioning compared with placebo. However, a global dampening of the reward system under serotonergic drugs is not intuitive considering clinical observations of their beneficial effects in the treatment of depression. Particularly, learning signals as coded in prediction error processing within the dopaminergic reward system can be assumed to be rather enhanced as antidepressant drugs have been demonstrated to facilitate the efficacy of psychotherapeutic interventions relying on learning processes. Within the same study sample, we now explored the effects of serotonergic and dopaminergic/noradrenergic antidepressants on prediction error signals compared with placebo by functional MRI. A total of 17 healthy male participants (mean age: 25.4 years) were investigated under the administration of paroxetine, bupropion and placebo for 7 days each within a randomized, double-blind, within-subject cross-over design. During functional MRI, we used an established monetary incentive task to explore neural prediction error signals within the bilateral nucleus accumbens as region of interest within the dopaminergic reward system. In contrast to diminished neural activations and subjective sexual functioning under the serotonergic agent paroxetine under visual erotic stimulation, we revealed unaffected or even enhanced neural prediction error processing within the nucleus accumbens under this antidepressant along with unaffected behavioural processing. Our study provides evidence that serotonergic antidepressants facilitate prediction error signalling and may support suggestions of beneficial effects of these agents on reinforced learning as an essential element in behavioural psychotherapy.

  9. Immediate extinction causes a less durable loss of performance than delayed extinction following either fear or appetitive conditioning.

    PubMed

    Woods, Amanda M; Bouton, Mark E

    2008-12-01

    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 all experiments, conditioning and extinction were accomplished in single sessions, and retention testing took place 24 h after extinction. In both fear and appetitive conditioning, immediate extinction (beginning 10 min after conditioning) caused a faster loss of responding than delayed extinction (beginning 24 h after conditioning). However, immediate extinction was less durable than delayed extinction: There was stronger spontaneous recovery during the final retention test. There was also substantial renewal of responding when the physical context was changed between immediate extinction and testing (Experiment 1). The results suggest that, in these two widely used conditioning preparations, immediate extinction does not erase or depotentiate the original learning, and instead creates a less permanent reduction in conditioned responding. Results did not support the possibility that the strong recovery after immediate extinction was due to a mismatch in the recent "context" provided by the presence or absence of a recent conditioning experience. Several other accounts are considered.

  10. The nature of extinction.

    PubMed

    Delord, Julien

    2007-09-01

    The phenomenon of species extinction raises more and more concern among ecologists facing the actual crisis of biodiversity. Scientific investigations of the causes and effects of extinction must be completed by a philosophical analysis of the concept of extinction that aims to clarify the meanings of the term 'extinction' and to analyse modalities, criteria and degrees of extinction. We will focus our attention on the apparent paradox of the possible 'resurrection' of species in the near future with the help of genetic biotechnology and cloning techniques. The ontological background of the extinction concept is analysed in relation to the idea of species as classes. We will also show that there is no simple analogy between death and species extinction, and develop a conceptualist and dualistic system of supra-individual entities (species vs. population), supported by an instrumentalist approach to genetic manipulations which transform species into interactive kinds, which can go extinct and be recreated.

  11. Learning for Life. Overcoming the Separation of Work and Learning. The Report of the National Advisory Panel on Skill Development Leave to the Minister of Employment and Immigration.

    ERIC Educational Resources Information Center

    Canadian Commission of Employment and Immigration, Ottawa (Ontario).

    Paid educational leave should become a regular feature of work life in Canada, according to the National Advisory Panel on Skill Development Leave. Following an eight-month study of the background and reasons for educational leave, the panel recommended that educational leave be established for the following reasons: (1) equity in allowing persons…

  12. Histamine facilitates consolidation of fear extinction.

    PubMed

    Bonini, Juliana Sartori; Da Silva, Weber Cláudio; Da Silveira, Clarice Kras Borges; Köhler, Cristiano André; Izquierdo, Iván; Cammarota, Martín

    2011-10-01

    Non-reinforced retrieval induces memory extinction, a phenomenon characterized by a decrease in the intensity of the learned response. This attribute has been used to develop extinction-based therapies to treat anxiety and post-traumatic stress disorders. Histamine modulates memory and anxiety but its role on fear extinction has not yet been evaluated. Therefore, using male Wistar rats, we determined the effect of the intra-hippocampal administration of different histaminergic agents on the extinction of step-down inhibitory avoidance (IA), a form of aversive learning. We found that intra-CA1 infusion of histamine immediately after non-reinforced retrieval facilitated consolidation of IA extinction in a dose-dependent manner. This facilitation was mimicked by the histamine N-methyltransferase inhibitor SKF91488 and the H2 receptor agonist dimaprit, reversed by the H2 receptor antagonist ranitidine, and unaffected by the H1 antagonist pyrilamine, the H3 antagonist thioperamide and the antagonist at the NMDA receptor (NMDAR) polyamine-binding site ifenprodil. Neither the H1 agonist 2-2-pyridylethylamine nor the NMDAR polyamine-binding site agonist spermidine affected the consolidation of extinction while the H3 receptor agonist imetit hampered it. Extinction induced the phosphorylation of ERK1 in dorsal CA1 while intra-CA1 infusion of the MEK inhibitor U0126 blocked extinction of the avoidance response. The extinction-induced phosphorylation of ERK1 was enhanced by histamine and dimaprit and blocked by ranitidine administered to dorsal CA1 after non-reinforced retrieval. Taken together, our data indicate that the hippocampal histaminergic system modulates the consolidation of fear extinction through a mechanism involving the H2-dependent activation of ERK signalling.

  13. Interoceptive conditioning with nicotine using extinction and re-extinction to assess stimulus similarity with bupropion.

    PubMed

    Charntikov, Sergios; deWit, Nicole R; Bevins, Rick A

    2014-11-01

    Bupropion is an atypical antidepressant that increases long-term quit rates of tobacco smokers. A better understanding of the relation between nicotine and this first-line medication may provide insight into improving treatment. For all experiments, rats first had nicotine (0.4 mg base/kg) and saline session intermixed; intermittent access to sucrose only occurred on nicotine session. Nicotine in this protocol comes to differentially control "anticipatory" dipper entries. To more closely examine the overlap in the interoceptive stimulus effects of nicotine and bupropion, we assessed whether subsequent prolonged and repeated non-reinforced (extinction) sessions with the bupropion stimulus could weaken responding to nicotine (i.e., transfer of extinction). We also examined whether retraining the discrimination after initial extinction and then conducting extinction again (i.e., re-extinction) with bupropion would affect responding. We found that bupropion (20 and 30 mg/kg) fully substituted for the nicotine stimulus in repeated 20-min extinction sessions. The extent of substitution in extinction did not necessarily predict performance in the transfer test (e.g., nicotine responding unchanged after extinction with 20 mg/kg bupropion). Generalization of extinction back to nicotine was not seen with 20 mg/kg bupropion even after increasing the number of extinction session from 6 to 24. Finally, there was evidence that learning in the initial extinction phase was retained in the re-extinction phase for nicotine and bupropion. These findings indicate that learning involving the nicotine stimuli are complex and that assessment approach for stimulus similarity changes conclusions regarding substitution by bupropion. Further research will be needed to identify whether such differences may be related to different facets of nicotine dependence and/or its treatment. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Interoceptive conditioning with nicotine using extinction and re-extinction to assess stimulus similarity with bupropion

    PubMed Central

    Charntikov, Sergios; deWit, Nicole R.; Bevins, Rick A

    2014-01-01

    Bupropion is an atypical antidepressant that increases long-term quit rates of tobacco smokers. A better understanding of the relation between nicotine and this first-line medication may provide insight into improving treatment. For all experiments, rats first had nicotine (0.4 mg base/kg) and saline session intermixed; intermittent access to sucrose only occurred on nicotine session. Nicotine in this protocol comes to differentially control “anticipatory” dipper entries. To more closely examine the overlap in the interoceptive stimulus effects of nicotine and bupropion, we assessed whether subsequent prolonged and repeated non-reinforced (extinction) sessions with the bupropion stimulus could weaken responding to nicotine (i.e., transfer of extinction). We also examined whether retraining the discrimination after initial extinction and then conducting extinction again (i.e., re-extinction) with bupropion would affect responding. We found that bupropion (20 and 30 mg/kg) fully substituted for the nicotine stimulus in repeated 20-min extinction sessions. The extent of substitution in extinction did not necessarily predict performance in the transfer test (e.g., nicotine responding unchanged after extinction with 20 mg/kg bupropion). Generalization of extinction back to nicotine was not seen with 20 mg/kg bupropion even after increasing the number of extinction session from 6 to 24. Finally, there was evidence that learning in the initial extinction phase was retained in the re-extinction phase for nicotine and bupropion. These findings indicate that learning involving the nicotine stimuli are complex and that assessment approach for stimulus similarity changes conclusions regarding substitution by bupropion. Further research will be needed to identify whether such differences may be related to different facets of nicotine dependence and/or its treatment. PMID:25080073

  15. Extinction of a classically conditioned response: red nucleus and interpositus.

    PubMed

    Robleto, Karla; Thompson, Richard F

    2008-03-05

    It is well established that the cerebellum and its associated circuitry are essential for classical conditioning of the eyeblink response and other discrete motor responses (e.g., limb flexion, head turn, etc.) learned with an aversive unconditioned stimulus. However, brain mechanisms underlying extinction of these responses are still relatively unclear. Behavioral studies have demonstrated extinction to be an active learning process distinct from acquisition. Accordingly, this current understanding of extinction has guided neural studies that have tried to identify possible brain structures that could support this new learning. However, whether extinction engages the same brain sites necessary for acquisition is not yet clear. This poses an overriding problem for understanding brain mechanisms necessary for extinction because such analysis cannot be done without first identifying brain sites and pathways involved in this phenomenon. Equally elusive is the validity of a behavioral theory of extinction that can account for the properties of extinction. In this study, we looked at the involvement of the interpositus and the red nucleus in extinction. Results show that, although inactivation of both nuclei blocks response expression, only inactivation of the interpositus has a detrimental effect on extinction. Moreover, this detrimental effect was completely removed when inactivation of the interpositus was paired with electrical stimulation of the red nucleus. These findings speak to the important role of cerebellar structures in the extinction of discrete motor responses and provide important insight as to the validity of a particular theory of extinction.

  16. [Extinction and Reconsolidation of Memory].

    PubMed

    Zuzina, A B; Balaban, P M

    2015-01-01

    Retrieval of memory followed by reconsolidation can strengthen a memory, while retrieval followed by extinction results in a decrease of memory performance due to weakening of existing memory or formation of a competing memory. In our study we analyzed the behavior and responses of identified neurons involved in the network underlying aversive learning in terrestrial snail Helix, and made an attempt to describe the conditions in which the retrieval of memory leads either to extinction or reconsolidation. In the network underlying the withdrawal behavior, sensory neurons, premotor interneurons, motor neurons, and modulatory for this network serotonergic neurons are identified and recordings from representatives of these groups were made before and after aversive learning. In the network underlying feeding behavior, the premotor modulatory serotonergic interneurons and motor neurons involved in motor program of feeding are identified. Analysis of changes in neural activity after aversive learning showed that modulatory neurons of feeding behavior do not demonstrate any changes (sometimes a decrease of responses to food was observed), while responses to food in withdrawal behavior premotor interneurons changed qualitatively, from under threshold EPSPs to spike discharges. Using a specific for serotonergic neurons neurotoxin 5,7-DiHT it was shown previously that the serotonergic system is necessary for the aversive learning, but is not necessary for maintenance and retrieval of this memory. These results suggest that the serotonergic neurons that are necessary as part of a reinforcement for developing the associative changes in the network may be not necessary for the retrieval of memory. The hypothesis presented in this review concerns the activity of the "reinforcement" serotonergic neurons that is suggested to be the gate condition for the choice between extinction/reconsolidation triggered by memory retrieval: if these serotonergic neurons do not respond during the

  17. Deepened Extinction following Compound Stimulus Presentation: Noradrenergic Modulation

    ERIC Educational Resources Information Center

    Janak, Patricia H.; Corbit, Laura H.

    2011-01-01

    Behavioral extinction is an active form of new learning involving the prediction of nonreward where reward has previously been present. The expression of extinction learning can be disrupted by the presentation of reward itself or reward-predictive stimuli (reinstatement) as well as the passage of time (spontaneous recovery) or contextual changes…

  18. Deepened Extinction following Compound Stimulus Presentation: Noradrenergic Modulation

    ERIC Educational Resources Information Center

    Janak, Patricia H.; Corbit, Laura H.

    2011-01-01

    Behavioral extinction is an active form of new learning involving the prediction of nonreward where reward has previously been present. The expression of extinction learning can be disrupted by the presentation of reward itself or reward-predictive stimuli (reinstatement) as well as the passage of time (spontaneous recovery) or contextual changes…

  19. Molecular mechanisms in hippocampus and basolateral amygdala but not in parietal or cingulate cortex are involved in extinction of one-trial avoidance learning.

    PubMed

    Myskiw, Jociane C; Fiorenza, Natalia G; Izquierdo, Luciana A; Izquierdo, Ivan

    2010-09-01

    The establishment of extinction of one-trial avoidance involves the dorsal hippocampus (DH) and basolateral amygdala (BLA), two areas that participate in its original consolidation. The posterior parietal (PARIE) and posterior cingulate (CING) cortices also participate in consolidation of this task but their role in extinction has not been explored. Here we study the effect on the extinction of one-trial avoidance in rats of three different drugs infused bilaterally into DH, BLA, PARIE or CING 5min before the first of four daily unreinforced test sessions: The glutamate NMDA receptor antagonist, AP5 (5.0microg/side),and the inhibitors of calcium-calmodulin dependent kinase II (CaMKII), KN-93 (0.3microg/side), or of the cAMP-dependent protein kinase (PKA), Rp-cAMPs (0.5microg/side) hindered extinction when given into DH or BLA. Levels of pPKA and pCaMKII increased in DH after the first extinction trial; in BLA only the CaMKII increase was seen. Thus, this pathway appears to participate in extinction in BLA at the "basal" levels, and at enhanced levels in DH. None of the treatments affected extinction when given into PARIE or CING. The present findings indicate that: (1) the DH and BLA are important for the initiation of extinction at the time of the first unreinforced retrieval session; (2) both the CaMKII and the PKA signaling pathway are necessary for the development of extinction in the two regions; (3) PARIE and CING are probably unrelated to extinction.

  20. Cold pressor test improves fear extinction in healthy men.

    PubMed

    Antov, Martin I; Melicherová, Ursula; Stockhorst, Ursula

    2015-04-01

    Fear extinction is an important paradigm to study the neural basis of anxiety and trauma- and stressor-related disorders and for modeling features of extinction learning and exposure-based psychotherapy. To date the effects of acute stress on extinction learning in humans are not well understood. Models of stress effects on emotional memory suggest that learning during the so-called first wave of the stress response will be enhanced. The first wave includes (among others) increases of noradrenaline in the brain and increased sympathetic tone, adrenaline and noradrenaline in the periphery while the second wave includes genomic glucocorticoid-actions. The cold pressor test (CPT) is a valid way to induce the first wave of the stress response. We thus hypothesized that the CPT will facilitate extinction. In a 2-day fear-conditioning procedure with 40 healthy men, using differential skin conductance responses as a measure of conditioned fear, we placed the CPT versus a control procedure prior to extinction training on Day 1. We tested for extinction learning on Day 1 and extinction retrieval on Day 2. During extinction training (Day 1) only the CPT-group showed a significant reduction in differential responding. This was still evident on Day 2, where the CPT group had less differential responding during early trials (retrieval) and a higher extinction retention index. This is the first human study to show that a simple procedure, triggering the first-wave stress response--the CPT--can effectively enhance fear extinction in humans.

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

    PubMed Central

    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 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. 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. PMID:25894546

  2. Is extinction forever?

    PubMed

    Smith-Patten, Brenda D; Bridge, Eli S; Crawford, Priscilla H C; Hough, Daniel J; Kelly, Jeffrey F; Patten, Michael A

    2015-05-01

    Mistrust of science has seeped into public perception of the most fundamental aspect of conservation-extinction. The term ought to be straightforward, and yet, there is a disconnect between scientific discussion and public views. This is not a mere semantic issue, rather one of communication. Within a population dynamics context, we say that a species went locally extinct, later to document its return. Conveying our findings matters, for when we use local extinction, an essentially nonsensical phrase, rather than extirpation, which is what is meant, then we contribute to, if not create outright, a problem for public understanding of conservation, particularly as local extinction is often shortened to extinction in media sources. The public that receives the message of our research void of context and modifiers comes away with the idea that extinction is not forever or, worse for conservation as a whole, that an extinction crisis has been invented. © The Author(s) 2015.

  3. Is extinction forever?

    PubMed Central

    Bridge, Eli S.; Crawford, Priscilla H. C.; Hough, Daniel J.; Kelly, Jeffrey F.; Patten, Michael A.

    2015-01-01

    Mistrust of science has seeped into public perception of the most fundamental aspect of conservation—extinction. The term ought to be straightforward, and yet, there is a disconnect between scientific discussion and public views. This is not a mere semantic issue, rather one of communication. Within a population dynamics context, we say that a species went locally extinct, later to document its return. Conveying our findings matters, for when we use local extinction, an essentially nonsensical phrase, rather than extirpation, which is what is meant, then we contribute to, if not create outright, a problem for public understanding of conservation, particularly as local extinction is often shortened to extinction in media sources. The public that receives the message of our research void of context and modifiers comes away with the idea that extinction is not forever or, worse for conservation as a whole, that an extinction crisis has been invented. PMID:25711479

  4. The Infralimbic Cortex Regulates the Consolidation of Extinction after Cocaine Self-Administration

    ERIC Educational Resources Information Center

    LaLumiere, Ryan T.; Niehoff, Kate E.; Kalivas, Peter W.

    2010-01-01

    The infralimbic cortex (IL) regulates the consolidation of extinction learning for fear conditioning. Whether the IL influences the consolidation of extinction learning for cocaine self-administration is unknown. To address this issue, male Sprague-Dawley rats underwent 2 wk of cocaine self-administration followed by extinction training. On the…

  5. The Infralimbic Cortex Regulates the Consolidation of Extinction after Cocaine Self-Administration

    ERIC Educational Resources Information Center

    LaLumiere, Ryan T.; Niehoff, Kate E.; Kalivas, Peter W.

    2010-01-01

    The infralimbic cortex (IL) regulates the consolidation of extinction learning for fear conditioning. Whether the IL influences the consolidation of extinction learning for cocaine self-administration is unknown. To address this issue, male Sprague-Dawley rats underwent 2 wk of cocaine self-administration followed by extinction training. On the…

  6. Effects of acute exercise on fear extinction in rats and exposure therapy in humans: Null findings from five experiments.

    PubMed

    Jacquart, Jolene; Roquet, Rheall F; Papini, Santiago; Powers, Mark B; Rosenfield, David; Smits, Jasper A J; Monfils, Marie-H

    2017-08-01

    Exposure therapy is an established learning-based intervention for the treatment of anxiety disorders with an average response rate of nearly 50%, leaving room for improvement. Emerging strategies to enhance exposure therapy in humans and fear extinction retention in animal models are primarily pharmacological. These approaches are limited as many patients report preferring non-pharmacological approaches in therapy. With general cognitive enhancement effects, exercise has emerged as a plausible non-pharmacological augmentation strategy. The present study tested the hypothesis that fear extinction and exposure therapy would be enhanced by a pre-training bout of exercise. We conducted four experiments with rats that involved a standardized conditioning and extinction paradigm and a manipulation of exercise. In a fifth experiment, we manipulated vigorous-intensity exercise prior to a standardized virtual reality exposure therapy session among adults with fear of heights. In experiments 1-4, exercise did not facilitate fear extinction, long-term memory, or fear relapse tests. In experiment 5, human participants showed an overall reduction in fear of heights but exercise did not enhance symptom improvement. Although acute exercise prior to fear extinction or exposure therapy, as operationalized in the present 5 studies, did not enhance outcomes, these results must be interpreted within the context of a broader literature that includes positive findings. Taken all together, this suggests that more research is necessary to identify optimal parameters and key individual differences so that exercise can be implemented successfully to treat anxiety disorders. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. A sphingolipid mechanism for behavioral extinction.

    PubMed

    Huston, Joseph P; Kornhuber, Johannes; Mühle, Christiane; Japtok, Lukasz; Komorowski, Mara; Mattern, Claudia; Reichel, Martin; Gulbins, Erich; Kleuser, Burkhard; Topic, Bianca; De Souza Silva, Maria A; Müller, Christian P

    2016-05-01

    Reward-dependent instrumental behavior must continuously be re-adjusted according to environmental conditions. Failure to adapt to changes in reward contingencies may incur psychiatric disorders like anxiety and depression. When an expected reward is omitted, behavior undergoes extinction. While extinction involves active re-learning, it is also accompanied by emotional behaviors indicative of frustration, anxiety, and despair (extinction-induced depression). Here, we report evidence for a sphingolipid mechanism in the extinction of behavior. Rapid extinction, indicating efficient re-learning, coincided with a decrease in the activity of the enzyme acid sphingomyelinase (ASM), which catalyzes turnover of sphingomyelin to ceramide, in the dorsal hippocampus of rats. The stronger the decline in ASM activity, the more rapid was the extinction. Sphingolipid-focused lipidomic analysis showed that this results in a decline of local ceramide species in the dorsal hippocampus. Ceramides shape the fluidity of lipid rafts in synaptic membranes and by that way can control neural plasticity. We also found that aging modifies activity of enzymes and ceramide levels in selective brain regions. Aging also changed how the chronic treatment with corticosterone (stress) or intranasal dopamine modified regional enzyme activity and ceramide levels, coinciding with rate of extinction. These data provide first evidence for a functional ASM-ceramide pathway in the brain involved in the extinction of learned behavior. This finding extends the known cellular mechanisms underlying behavioral plasticity to a new class of membrane-located molecules, the sphingolipids, and their regulatory enzymes, and may offer new treatment targets for extinction- and learning-related psychopathological conditions. Sphingolipids are common lipids in the brain which form lipid domains at pre- and postsynaptic membrane compartments. Here we show a decline in dorsal hippocampus ceramide species together with a

  8. Secondary extinctions of biodiversity.

    PubMed

    Brodie, Jedediah F; Aslan, Clare E; Rogers, Haldre S; Redford, Kent H; Maron, John L; Bronstein, Judith L; Groves, Craig R

    2014-12-01

    Extinctions beget further extinctions when species lose obligate mutualists, predators, prey, or hosts. Here, we develop a conceptual model of species and community attributes affecting secondary extinction likelihood, incorporating mechanisms that buffer organisms against partner loss. Specialized interactors, including 'cryptic specialists' with diverse but nonredundant partner assemblages, incur elevated risk. Risk is also higher for species that cannot either evolve new traits following partner loss or obtain novel partners in communities reorganizing under changing environmental conditions. Partner loss occurs alongside other anthropogenic impacts; multiple stressors can circumvent ecological buffers, enhancing secondary extinction risk. Stressors can also offset each other, reducing secondary extinction risk, a hitherto unappreciated phenomenon. This synthesis suggests improved conservation planning tactics and critical directions for research on secondary extinctions. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Amphetamine and Extinction of Cued Fear

    PubMed Central

    Carmack, Stephanie A.; Wood, Suzanne C.; Anagnostaras, Stephan G.

    2010-01-01

    Much research is focused on developing novel drugs to improve memory. In particular, psychostimulants have been shown to enhance memory and have a long history of safe use in humans. In prior work, we have shown that very low doses of amphetamine administered before training on a Pavlovian fear-conditioning task can dramatically facilitate the acquisition of cued fear. The current experiment sought to expand these findings to the extinction of cued fear, a well-known paradigm with therapeutic implications for learned phobias and post-traumatic stress disorder. If extinction reflects new learning, one might expect drugs that enhance the acquisition of cued fear to also enhance the extinction of cued fear. This experiment examined whether 0.005 or 0.05 mg/kg of d-amphetamine (therapeutic doses shown to enhance acquisition) also enhance the extinction of cued fear. Contrary to our hypothesis, amphetamine did not accelerate extinction. Thus, at doses that enhance acquisition of conditioned fear, amphetamine does not appear to enhance extinction. PMID:19853020

  10. Mass extinction: a commentary

    NASA Technical Reports Server (NTRS)

    Raup, D. M.

    1987-01-01

    Four neocatastrophist claims about mass extinction are currently being debated; they are that: 1, the late Cretaceous mass extinction was caused by large body impact; 2, as many as five other major extinctions were caused by impact; 3, the timing of extinction events since the Permian is uniformly periodic; and 4, the ages of impact craters on Earth are also periodic and in phase with the extinctions. Although strongly interconnected the four claims are independent in the sense that none depends on the others. Evidence for a link between impact and extinction is strong but still needs more confirmation through bed-by-bed and laboratory studies. An important area for future research is the question of whether extinction is a continuous process, with the rate increasing at times of mass extinctions, or whether it is episodic at all scales. If the latter is shown to be generally true, then species are at risk of extinction only rarely during their existence and catastrophism, in the sense of isolated events of extreme stress, is indicated. This is line of reasoning can only be considered an hypothesis for testing. In a larger context, paleontologists may benefit from a research strategy that looks to known Solar System and Galactic phenomena for predictions about environmental effects on earth. The recent success in the recognition of Milankovitch Cycles in the late Pleistocene record is an example of the potential of this research area.

  11. Mass extinction: a commentary.

    PubMed

    Raup, D M

    1987-01-01

    Four neocatastrophist claims about mass extinction are currently being debated; they are that: 1, the late Cretaceous mass extinction was caused by large body impact; 2, as many as five other major extinctions were caused by impact; 3, the timing of extinction events since the Permian is uniformly periodic; and 4, the ages of impact craters on Earth are also periodic and in phase with the extinctions. Although strongly interconnected the four claims are independent in the sense that none depends on the others. Evidence for a link between impact and extinction is strong but still needs more confirmation through bed-by-bed and laboratory studies. An important area for future research is the question of whether extinction is a continuous process, with the rate increasing at times of mass extinctions, or whether it is episodic at all scales. If the latter is shown to be generally true, then species are at risk of extinction only rarely during their existence and catastrophism, in the sense of isolated events of extreme stress, is indicated. This is line of reasoning can only be considered an hypothesis for testing. In a larger context, paleontologists may benefit from a research strategy that looks to known Solar System and Galactic phenomena for predictions about environmental effects on earth. The recent success in the recognition of Milankovitch Cycles in the late Pleistocene record is an example of the potential of this research area.

  12. Gradual extinction reduces reinstatement

    PubMed Central

    Shiban, Youssef; Wittmann, Jasmin; Weißinger, Mara; Mühlberger, Andreas

    2015-01-01

    The current study investigated whether gradually reducing the frequency of aversive stimuli during extinction can prevent the return of fear. Thirty-one participants of a three-stage procedure (acquisition, extinction and a reinstatement test on day 2) were randomly assigned to a standard extinction (SE) and gradual extinction (GE) procedure. The two groups differed only in the extinction procedure. While the SE group ran through a regular extinction process without any negative events, the frequency of the aversive stimuli during the extinction phase was gradually reduced for the GE group. The unconditioned stimulus (US) was an air blast (5 bar, 10 ms). A spider and a scorpion were used as conditioned stimuli (CS). The outcome variables were contingency ratings and physiological measures (skin conductance response, SCR and startle response). There were no differences found between the two groups for the acquisition and extinction phases concerning contingency ratings, SCR, or startle response. GE compared to SE significantly reduced the return of fear in the reinstatement test for the startle response but not for SCR or contingency ratings. This study was successful in translating the findings in rodent to humans. The results suggest that the GE process is suitable for increasing the efficacy of fear extinction. PMID:26441581

  13. Cannabinoid facilitation of fear extinction memory recall in humans.

    PubMed

    Rabinak, Christine A; Angstadt, Mike; Sripada, Chandra S; Abelson, James L; Liberzon, Israel; Milad, Mohammed R; Phan, K Luan

    2013-01-01

    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 the cannabinoid system during extinction learning enhances fear extinction and its retention. Specifically, CB1 receptor agonists, such as Δ9-tetrahydrocannibinol (THC), can facilitate extinction recall by preventing recovery of extinguished fear in rats. However, this phenomenon has not been investigated in humans. We conducted a study using a randomized, double-blind, placebo-controlled, between-subjects design, coupling a standard Pavlovian fear extinction paradigm and simultaneous skin conductance response (SCR) recording with an acute pharmacological challenge with oral dronabinol (synthetic THC) or placebo (PBO) 2 h prior to extinction learning in 29 healthy adult volunteers (THC = 14; PBO = 15) and tested extinction retention 24 h after extinction learning. Compared to subjects that received PBO, subjects that received THC showed low SCR to a previously extinguished CS when extinction memory recall was tested 24 h after extinction learning, suggesting that THC prevented the recovery of fear. These results provide the first evidence that pharmacological enhancement of extinction learning is feasible in humans using cannabinoid system modulators, which may thus warrant further development and clinical testing. This article is part of a Special Issue entitled 'Cognitive Enhancers'.

  14. Induction of fear extinction with hippocampal-infralimbic BDNF.

    PubMed

    Peters, Jamie; Dieppa-Perea, Laura M; Melendez, Loyda M; Quirk, Gregory J

    2010-06-04

    The extinction of conditioned fear memories requires plasticity in the infralimbic medial prefrontal cortex (IL mPFC), but little is known about the molecular mechanisms involved. Brain-derived neurotrophic factor (BDNF) is a key mediator of synaptic plasticity in multiple brain areas. In rats subjected to auditory fear conditioning, BDNF infused into the IL mPFC reduced conditioned fear for up to 48 hours, even in the absence of extinction training, which suggests that BDNF substituted for extinction. Similar to extinction, BDNF-induced reduction in fear required N-methyl-D-aspartate receptors and did not erase the original fear memory. Rats failing to learn extinction showed reduced BDNF in hippocampal inputs to the IL mPFC, and augmenting BDNF in this pathway prevented extinction failure. Hence, boosting BDNF activity in hippocampal-infralimbic circuits may ameliorate disorders of learned fear.

  15. The fossil record of the sixth extinction.

    PubMed

    Plotnick, Roy E; Smith, Felisa A; Lyons, S Kathleen

    2016-05-01

    Comparing the magnitude of the current biodiversity crisis with those in the fossil record is difficult without an understanding of differential preservation. Integrating data from palaeontological databases with information on IUCN status, ecology and life history characteristics of contemporary mammals, we demonstrate that only a small and biased fraction of threatened species (< 9%) have a fossil record, compared with 20% of non-threatened species. We find strong taphonomic biases related to body size and geographic range. Modern species with a fossil record tend to be large and widespread and were described in the 19(th) century. The expected magnitude of the current extinction based only on species with a fossil record is about half of that of one based on all modern species; values for genera are similar. The record of ancient extinctions may be similarly biased, with many species having originated and gone extinct without leaving a tangible record. © 2016 John Wiley & Sons Ltd/CNRS.

  16. A window of vulnerability: impaired fear extinction in adolescence.

    PubMed

    Baker, Kathryn D; Den, Miriam L; Graham, Bronwyn M; Richardson, Rick

    2014-09-01

    There have been significant advances made towards understanding the processes mediating extinction of learned fear. However, despite being of clear theoretical and clinical significance, very few studies have examined fear extinction in adolescence, which is often described as a developmental window of vulnerability to psychological disorders. This paper reviews the relatively small body of research examining fear extinction in adolescence. A prominent finding of this work is that adolescents, both humans and rodents, exhibit a marked impairment in extinction relative to both younger (e.g., juvenile) and older (e.g., adult) groups. We then review some potential mechanisms that could produce the striking extinction deficit observed in adolescence. For example, one neurobiological candidate mechanism for impaired extinction in adolescence involves changes in the functional connectivity within the fear extinction circuit, particularly between prefrontal cortical regions and the amygdala. In addition, we review research on emotion regulation and attention processes that suggests that developmental changes in attention bias to threatening cues may be a cognitive mechanism that mediates age-related differences in extinction learning. We also examine how a differential reaction to chronic stress in adolescence impacts upon extinction retention during adolescence as well as in later life. Finally, we consider the findings of several studies illustrating promising approaches that overcome the typically-observed extinction impairments in adolescent rodents and that could be translated to human adolescents. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Does fear extinction in the laboratory predict outcomes of exposure therapy? A treatment analog study.

    PubMed

    Forcadell, Eduard; Torrents-Rodas, David; Vervliet, Bram; Leiva, David; Tortella-Feliu, Miquel; Fullana, Miquel A

    2017-09-08

    Fear extinction models have a key role in our understanding of anxiety disorders and their treatment with exposure therapy. Here, we tested whether individual differences in fear extinction learning and fear extinction recall in the laboratory were associated with the outcomes of an exposure therapy analog (ETA). Fifty adults with fear of spiders participated in a two-day fear-learning paradigm assessing fear extinction learning and fear extinction recall, and then underwent a brief ETA. Correlational analyses indicated that enhanced extinction learning was associated with better ETA outcome. Our results partially support the idea that individual differences in fear extinction learning may be associated with exposure therapy outcome, but suggest that further research in this area is needed. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Beliefs about Human Extinction

    SciTech Connect

    Tonn, Bruce Edward

    2009-11-01

    This paper presents the results of a web-based survey about futures issues. Among many questions, respondents were asked whether they believe humans will become extinct. Forty-five percent of the almost 600 respondents believe that humans will become extinct. Many of those holding this believe felt that humans could become extinct within 500-1000 years. Others estimated extinction 5000 or more years into the future. A logistic regression model was estimated to explore the bases for this belief. It was found that people who describe themselves a secular are more likely to hold this belief than people who describe themselves as being Protestant. Older respondents and those who believe that humans have little control over their future also hold this belief. In addition, people who are more apt to think about the future and are better able to imagine potential futures tend to also believe that humans will become extinct.

  19. Extinction and climate change.

    PubMed

    Thomas, Chris D; Williamson, Mark

    2012-02-22

    Arising from F. He & S. P. Hubbell 473, 368-371 (2011). Statistical relationships between habitat area and the number of species observed (species-area relationships, SARs) are sometimes used to assess extinction risks following habitat destruction or loss of climatic suitability. He and Hubbell argue that the numbers of species confined to-rather than observed in-different areas (endemics-area relationships, EARs) should be used instead of SARs, and that SAR-based extinction estimates in the literature are too high. We suggest that He and Hubbell's SAR estimates are biased, that the empirical data they use are not appropriate to calculate extinction risks, and that their statements about extinction risks from climate change do not take into account non-SAR-based estimates or recent observations. Species have already responded to climate change in a manner consistent with high future extinction risks.

  20. Extinction of chained instrumental behaviors: Effects of consumption extinction on procurement responding.

    PubMed

    Thrailkill, Eric A; Bouton, Mark E

    2016-03-01

    Operant behavior is typically organized into sequences of responses that eventually lead to a reinforcer. Response elements can be categorized as those that directly lead to reward consumption (i.e., a consumption response) and those that lead to the opportunity to make the consumption response (i.e., a procurement response). These responses often differ topographically and in terms of the discriminative stimuli that set the occasion for them. We have recently shown that extinction of the procurement response acts to weaken the specific associated consumption response, and that active inhibition of the procurement response is required for this effect. To expand the analysis of the associative structure of chains, in the present experiments we asked the reverse question: whether extinction of consumption behavior results in a decrease in the associated procurement response in a discriminated heterogeneous chain. In Experiment 1, extinction of consumption alone led to an attenuation of the associated procurement response only when rats were allowed to make the consumption response in extinction. Exposure to the consumption stimulus alone was not sufficient to produce weakened procurement responding. In Experiment 2, rats learned two distinct heterogeneous chains, and extinction of one consumption response specifically weakened the procurement response associated with it. The results add to the evidence suggesting that rats learn a highly specific associative structure in behavior chains, emphasizing the role of learning response inhibition in extinction.

  1. Behavioral and neural analysis of extinction.

    PubMed

    Myers, Karyn M; Davis, Michael

    2002-11-14

    The neural mechanisms by which fear is inhibited are poorly understood at the present time. Behaviorally, a conditioned fear response may be reduced in intensity through a number of means. Among the simplest of these is extinction, a form of learning characterized by a decrease in the amplitude and frequency of a conditioned response when the conditioned stimulus that elicits it is repeatedly nonreinforced. Because clinical interventions for patients suffering from fear dysregulation seek to inhibit abnormal, presumably learned fear responses, an understanding of fear extinction is likely to inform and increase the efficacy of these forms of treatment. This review considers the behavioral, cellular, and molecular literatures on extinction and presents the most recent advances in our understanding while identifying issues that require considerable further research.

  2. Leaving School — learning at SEA: Regular high school education alongside polar research, not only during IPY

    NASA Astrophysics Data System (ADS)

    Gatti, S.

    2006-12-01

    Against the background of unsatisfactory results from the international OECD study PISA (Program for International Student Assessment), Germany is facing a period of intense school reforms. Looking back at a tradition of school culture with too few changes during the last century, quick and radical renewal of the school system is rather unlikely. Furthermore students are increasingly turning away from natural sciences. The AWI aims at providing impulses for major changes in the schooling system and is offering solid science education not only for university students but also for a much younger audience. All efforts towards this goal are interconnected within the project SEA (Science & Education @ the AWI). Fife years ago the AWI started HIGHSEA (High school of SEA). Each year 22 high school students (grade 11) are admitted to HIGHSEA spending their last three years of school not at school but at the institute. Four subjects (biology as a major, chemistry, math and English as accessory subjects) are combined and taught fully integrated. Students leave their schools for two days each week to study, work and explore all necessary topics at the AWI. All of the curricular necessities of the four subjects are being met. After rearrangement of the temporal sequencing conceptual formulation of four major questions around AWI-topics was possible. Students are taught by teachers of the cooperating schools as well as by scientists of the AWI. Close links and intense cooperation between all three groups are the basis of fundamental changes in teaching and learning climate. For each group of students we organize a short research expedition: in August 2005 we worked in the high Arctic, in January and February 2006 we performed measurements at two eastern Atlantic seamounts. Even if the amount of data coming from these expeditions is comparatively small they still contribute to ongoing research projects of the oceanographic department. The first two groups of students finished

  3. Extinction and the fossil record

    NASA Technical Reports Server (NTRS)

    Sepkoski, J. J. Jr; Sepkoski JJ, ,. J. r. (Principal Investigator)

    1994-01-01

    The author examines evidence of mass extinctions in the fossil record and searches for reasons for such large extinctions. Five major mass extinctions eliminated at least 40 percent of animal genera in the oceans and from 65 to 95 percent of ocean species. Questions include the occurrence of gradual or catastrophic extinctions, causes, environment, the capacity of a perturbation to cause extinctions each time it happens, and the possibility and identification of complex events leading to a mass extinction.

  4. Extinction and the fossil record

    NASA Technical Reports Server (NTRS)

    Sepkoski, J. J. Jr; Sepkoski JJ, ,. J. r. (Principal Investigator)

    1994-01-01

    The author examines evidence of mass extinctions in the fossil record and searches for reasons for such large extinctions. Five major mass extinctions eliminated at least 40 percent of animal genera in the oceans and from 65 to 95 percent of ocean species. Questions include the occurrence of gradual or catastrophic extinctions, causes, environment, the capacity of a perturbation to cause extinctions each time it happens, and the possibility and identification of complex events leading to a mass extinction.

  5. Adrenergic Transmission Facilitates Extinction of Conditional Fear in Mice

    ERIC Educational Resources Information Center

    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…

  6. Adrenergic Transmission Facilitates Extinction of Conditional Fear in Mice

    ERIC Educational Resources Information Center

    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…

  7. [Effects of dehydroepiandrosterone sulfate and dizocilpine on memory trace extinction in aggressive and submissive mice].

    PubMed

    Dubrovina, N I; Tomilenko, R A; Obut, T A

    2006-01-01

    It was shown that injections of NMDA receptor antagonist dizocilpine and neurosteroid dehydroepiandrosterone sulfate (DHEAS) and sequential injections of these substances had different effects on learning and extinction of passive avoidance in aggressive and submissive mice. In aggressive mice, dizocilpine impaired and DHEAS did not change learning and retention. However, being injected after dizocilpine, DHEAS blocked the defect of memory trace retrieval induced by dizocilpine. In submissive mice, dizocilpine impaired learning and prolonged extinction of the learned habit. Injection of DHEAS prolonged the extinction in a similar way. Under conditions of sequential injections, DHEAS did not change the suppressive effect of dizocilpine on learning and was not effective in prolongation of extinction.

  8. Is extinction age dependent?

    USGS Publications Warehouse

    Doran, N.A.; Arnold, A.J.; Parker, W.C.; Huffer, F.W.

    2006-01-01

    Age-dependent extinction is an observation with important biological implications. Van Valen's Red Queen hypothesis triggered three decades of research testing its primary implication: that age is independent of extinction. In contrast to this, later studies with species-level data have indicated the possible presence of age dependence. Since the formulation of the Red Queen hypothesis, more powerful tests of survivorship models have been developed. This is the first report of the application of the Cox Proportional Hazards model to paleontological data. Planktonic foraminiferal morphospecies allow the taxonomic and precise stratigraphic resolution necessary for the Cox model. As a whole, planktonic foraminiferal morphospecies clearly show age-dependent extinction. In particular, the effect is attributable to the presence of shorter-ranged species (range < 4 myr) following extinction events. These shorter-ranged species also possess tests with unique morphological architecture. The morphological differences are probably epiphenomena of underlying developmental and heterochronic processes of shorter-ranged species that survived various extinction events. Extinction survivors carry developmental and morphological characteristics into postextinction recovery times, and this sets them apart from species populations established independently of extinction events. Copyright ?? 2006, SEPM (Society for Sedimentary Geology).

  9. IMPAIRED FEAR EXTINCTION ASSOCIATED WITH PTSD INCREASES WITH HOURS-SINCE-WAKING.

    PubMed

    Zuj, Daniel V; Palmer, Matthew A; Hsu, Chia-Ming K; Nicholson, Emma L; Cushing, Pippa J; Gray, Kate E; Felmingham, Kim L

    2016-03-01

    Prior research has demonstrated that time-of-day may play an important role in the extinction of conditioned fear, with extinction better learned earlier in the day rather than later. Impaired fear extinction memory is widely considered a key mechanism of posttraumatic stress disorder (PTSD). The relationship between fear extinction and PTSD symptoms may be moderated by hours-since-waking. In the present experiment, we examined whether hours-since-waking would moderate fear extinction learning ability in a clinical PTSD sample (n = 15), compared to trauma-exposed (n = 33) and nonexposed controls (n = 22). Participants completed a standardized differential fear conditioning and extinction paradigm, providing skin conductance response measures to quantify conditioned responding. Mixed-model analysis of variance revealed a PTSD-specific impairment in extinction learning ability in the late extinction phase. A moderation analysis showed that hours-since-waking was a significant moderator of the relationship between impaired late extinction and PTSD symptoms. Specifically, we found that participants with higher PTSD symptoms demonstrated poorer fear extinction learning ability as they were awake for longer. The results of the current study add to a growing literature indicating deficits in fear extinction learning in PTSD samples, compared to trauma-exposed and nonexposed controls. These results support previous findings that fear extinction is impaired later in the day, and extends this to a clinical sample, suggesting that exposure-therapy may be optimized by scheduling sessions in the morning. © 2016 Wiley Periodicals, Inc.

  10. Protection from extinction.

    PubMed

    Rescorla, Robert A

    2003-05-01

    The effect of the presence of a conditioned inhibitor on extinction of excitatory conditioning was studied in one magazine approach and three autoshaping experiments using rats and pigeons. In each case, the presence of an inhibitor reduced responding to an exciter during extinction but allowed substantial recovery of responding to that exciter when subsequently tested separately. Control stimuli with a history of being irrelevant to reinforcement or being nonreinforced had less of a protective effect. This constitutes a clear demonstration of protection from extinction, a phenomenon of substantial theoretical and applied importance.

  11. Population Health and Paid Parental Leave: What the United States Can Learn from Two Decades of Research

    PubMed Central

    Burtle, Adam; Bezruchka, Stephen

    2016-01-01

    Over the last two decades, numerous studies have suggested that dedicated time for parents to be with their children in the earliest months of life offers significant benefits to child health. The United States (US) is the only wealthy nation without a formalized policy guaranteeing workers paid time off when they become new parents. As individual US states consider enacting parental leave policies, there is a significant opportunity to decrease health inequities and build a healthier American population. This document is intended as a critical review of the present evidence for the association between paid parental leave and population health. PMID:27417618

  12. Population Health and Paid Parental Leave: What the United States Can Learn from Two Decades of Research.

    PubMed

    Burtle, Adam; Bezruchka, Stephen

    2016-06-01

    Over the last two decades, numerous studies have suggested that dedicated time for parents to be with their children in the earliest months of life offers significant benefits to child health. The United States (US) is the only wealthy nation without a formalized policy guaranteeing workers paid time off when they become new parents. As individual US states consider enacting parental leave policies, there is a significant opportunity to decrease health inequities and build a healthier American population. This document is intended as a critical review of the present evidence for the association between paid parental leave and population health.

  13. [GABA-Receptors in Modulation of Fear Memory Extinction].

    PubMed

    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.

  14. Concurrent extinction does not render appetitive conditioning context specific.

    PubMed

    Nelson, James Byron; Lombas, Sebastián; Léon, Samuel P

    2011-03-01

    In an experiment with rats, an appetitive conditioning method was used to investigate the generality of the hypothesis that extinction should arouse attention to contextual cues, resulting in all learning in that context becoming context specific. Rats received appetitive conditioning with a tone either while extinction of a flasher occurred (Group With Extinction) or while it did not (Group No Extinction). Half of each group was subsequently tested in extinction in the context in which training had taken place or in a different context. The results revealed a three-way interaction of extinction and context with trials, in a direction opposite to the one the hypothesis would suggest. When rats were tested in a different context, there was generally better responding in Group With Extinction than in Group No Extinction. In the same context, there was generally lower responding in Group With Extinction than in Group No Extinction. Subsequent testing showed an ABA recovery effect. Results are discussed in terms of the challenges they pose for the revised retrieval theory presented by Callejas-Aguilera and Rosas (2011).

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

    PubMed Central

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

    2016-01-01

    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

  16. Glutamate Receptors in Extinction and Extinction-Based Therapies for Psychiatric Illness

    PubMed Central

    Myers, Karyn M; Carlezon, William A; Davis, Michael

    2011-01-01

    Some psychiatric illnesses involve a learned component. For example, in posttraumatic stress disorder, memories triggered by trauma-associated cues trigger fear and anxiety, and in addiction, drug-associated cues elicit drug craving and withdrawal. Clinical interventions to reduce the impact of conditioned cues in eliciting these maladaptive conditioned responses are likely to be beneficial. Extinction is a method of lessening conditioned responses and involves repeated exposures to a cue in the absence of the event it once predicted. We believe that an improved understanding of the behavioral and neurobiological mechanisms of extinction will allow extinction-like procedures in the clinic to become more effective. Research on the role of glutamate—the major excitatory neurotransmitter in the mammalian brain—in extinction has led to the development of pharmacotherapeutics to enhance the efficacy of extinction-based protocols in clinical populations. In this review, we describe what has been learned about glutamate actions at its three major receptor types (N-methyl--aspartate (NMDA) receptors, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, and metabotropic glutamate receptors) in the extinction of conditioned fear, drug craving, and withdrawal. We then discuss how these findings have been applied in clinical research. PMID:20631689

  17. Extinction of oscillating populations

    NASA Astrophysics Data System (ADS)

    Smith, Naftali R.; Meerson, Baruch

    2016-03-01

    Established populations often exhibit oscillations in their sizes that, in the deterministic theory, correspond to a limit cycle in the space of population sizes. If a population is isolated, the intrinsic stochasticity of elemental processes can ultimately bring it to extinction. Here we study extinction of oscillating populations in a stochastic version of the Rosenzweig-MacArthur predator-prey model. To this end we develop a WKB (Wentzel, Kramers and Brillouin) approximation to the master equation, employing the characteristic population size as the large parameter. Similar WKB theories have been developed previously in the context of population extinction from an attracting multipopulation fixed point. We evaluate the extinction rates and find the most probable paths to extinction from the limit cycle by applying Floquet theory to the dynamics of an effective four-dimensional WKB Hamiltonian. We show that the entropic barriers to extinction change in a nonanalytic way as the system passes through the Hopf bifurcation. We also study the subleading pre-exponential factors of the WKB approximation.

  18. Fear extinction and relapse: state of the art.

    PubMed

    Vervliet, Bram; Craske, Michelle G; Hermans, Dirk

    2013-01-01

    Exposure-based treatments for clinical anxiety generally are very effective, but relapse is not uncommon. Likewise, laboratory studies have shown that conditioned fears are easy to extinguish, but they recover easily. This analogy is striking, and numerous fear extinction studies have been published that highlight the processes responsible for the extinction and return of acquired fears. This review examines and integrates the most important results from animal and human work. Overall, the results suggest that fear extinction is relatively easy to "learn" but difficult to "remember." It follows that treatments will benefit from an enhanced focus on the long-term retrieval of fear extinction. We review the available studies on the prevention of return of fear and the prospects of weakening fear memories forever. We show that the behavioral principles outlined in learning theory provide a continuous inspiration for preclinical (neurobiological) and clinical research on the extinction and return of fear.

  19. Acute stress impairs the retrieval of extinction memory in humans.

    PubMed

    Raio, Candace M; Brignoni-Perez, Edith; Goldman, Rachel; Phelps, Elizabeth A

    2014-07-01

    Extinction training is a form of inhibitory learning that allows an organism to associate a previously aversive cue with a new, safe outcome. Extinction does not erase a fear association, but instead creates a competing association that may or may not be retrieved when a cue is subsequently encountered. Characterizing the conditions under which extinction learning is expressed is important to enhancing the treatment of anxiety disorders that rely on extinction-based exposure therapy as a primary treatment technique. The ventromedial prefrontal cortex, which plays a critical role in the expression of extinction memory, has been shown to be functionally impaired after stress exposure. Further, recent work in rodents has demonstrated that exposure to stress leads to deficits in extinction retrieval, although this has yet to be tested in humans. To explore how stress might influence extinction retrieval in humans, participants underwent a differential aversive learning paradigm, in which one image was probabilistically paired with an aversive shock while the other image denoted safety. Extinction training directly followed, at which point reinforcement was omitted. A day later, participants returned to the lab and either completed an acute stress manipulation (i.e., cold pressor), or a control task, before undergoing an extinction retrieval test. Skin conductance responses and salivary cortisol concentrations were measured throughout each session as indices of fear arousal and neuroendocrine stress response, respectively. The efficacy of our stress induction was established by observing significant increases in cortisol for the stress condition only. We examined extinction retrieval by comparing conditioned responses during the last trial of extinction (day 1) with that of the first trial of re-extinction (day 2). Groups did not differ on initial fear acquisition or extinction, however, a day later participants in the stress group (n=27) demonstrated significantly

  20. All about Endangered and Extinct Animals. Animal Life for Children. [Videotape].

    ERIC Educational Resources Information Center

    2000

    While there are thousands of different animals in the world, some have been extinct for many years and others are on the verge of extinction. In this videotape, students learn about the natural and man-made factors that lead to the endangerment and extinction of animals. Children find out why it is essential for people to help all forms of…

  1. Role of Medial Prefrontal Cortex Narp in the Extinction of Morphine Conditioned Place Preference

    ERIC Educational Resources Information Center

    Blouin, Ashley M.; Han, Sungho; Pearce, Anne M.; Cheng, KaiLun; Lee, JongAh J.; Johnson, Alexander W.; Wang, Chuansong; During, Matthew J.; Holland, Peter C.; Shaham, Yavin; Baraban, Jay M.; Reti, Irving M.

    2013-01-01

    Narp knockout (KO) mice demonstrate an impaired extinction of morphine conditioned place preference (CPP). Because the medial prefrontal cortex (mPFC) has been implicated in extinction learning, we tested whether Narp cells in this region play a role in the extinction of morphine CPP. We found that intracranial injections of adenoassociated virus…

  2. All about Endangered and Extinct Animals. Animal Life for Children. [Videotape].

    ERIC Educational Resources Information Center

    2000

    While there are thousands of different animals in the world, some have been extinct for many years and others are on the verge of extinction. In this videotape, students learn about the natural and man-made factors that lead to the endangerment and extinction of animals. Children find out why it is essential for people to help all forms of…

  3. Role of Medial Prefrontal Cortex Narp in the Extinction of Morphine Conditioned Place Preference

    ERIC Educational Resources Information Center

    Blouin, Ashley M.; Han, Sungho; Pearce, Anne M.; Cheng, KaiLun; Lee, JongAh J.; Johnson, Alexander W.; Wang, Chuansong; During, Matthew J.; Holland, Peter C.; Shaham, Yavin; Baraban, Jay M.; Reti, Irving M.

    2013-01-01

    Narp knockout (KO) mice demonstrate an impaired extinction of morphine conditioned place preference (CPP). Because the medial prefrontal cortex (mPFC) has been implicated in extinction learning, we tested whether Narp cells in this region play a role in the extinction of morphine CPP. We found that intracranial injections of adenoassociated virus…

  4. The infralimbic cortex regulates the consolidation of extinction after cocaine self-administration.

    PubMed

    LaLumiere, Ryan T; Niehoff, Kate E; Kalivas, Peter W

    2010-04-01

    The infralimbic cortex (IL) regulates the consolidation of extinction learning for fear conditioning. Whether the IL influences the consolidation of extinction learning for cocaine self-administration is unknown. To address this issue, male Sprague-Dawley rats underwent 2 wk of cocaine self-administration followed by extinction training. On the first 5 d of extinction, rats underwent brief (15- or 30-min) extinction sessions and received intra-IL microinjections immediately after each extinction session. On days 6-12 of extinction, rats underwent full-length (2-h) extinction sessions that were used to assess the retention of the extinction learning from the short sessions. IL inactivation via microinjections of the GABA agonists baclofen and muscimol (BM) immediately after the extinction sessions (days 1-5) impaired the retention of extinction learning. Control experiments demonstrated that this effect was not due to inactivation of the prelimbic cortex or due to effects of the drugs on the subsequent day's behavior. In contrast, post-training intra-IL microinjections of the allosteric AMPA receptor potentiator 4-[2-(phenylsulfonylamino)ethylthio]-2,6-difluorophenoxyacetamide (PEPA) enhanced retention of the extinction learning. As evidence suggests a role for the beta-adrenergic receptors in memory consolidation, other rats received microinjections of the beta(2)-adrenergic receptor agonist clenbuterol or antagonist ICI-118,551 (ICI). Post-training intra-IL administration of clenbuterol or pre-training administration of ICI enhanced or impaired, respectively, the retention of extinction learning. These data indicate that the IL, and specifically the glutamatergic and beta-adrenergic systems in the IL, regulates the consolidation of extinction of cocaine self-administration and that the IL can be manipulated to influence the retention of extinction.

  5. Candesartan Ameliorates Impaired Fear Extinction Induced by Innate Immune Activation

    PubMed Central

    Quiñones, María M.; Maldonado, Lizette; Velazquez, Bethzaly; Porter, James T.

    2015-01-01

    Patients with post-traumatic stress disorder (PTSD) tend to show signs of a relatively increased inflammatory state suggesting that activation of the immune system may contribute to the development of PTSD. In the present study, we tested whether activation of the innate immune system can disrupt acquisition or recall of auditory fear extinction using an animal model of PTSD. Male adolescent rats received auditory fear conditioning in context A. The next day, an intraperitoneal injection of lipopolysaccharide (LPS; 100 μg/kg) prior to auditory fear extinction in context B impaired acquisition and recall of extinction. LPS (100 μg/kg) given after extinction training did not impair extinction recall suggesting that LPS did not affect consolidation of extinction. In contrast to cued fear extinction, contextual fear extinction was not affected by prior injection of LPS (100 μg/kg). Although LPS also reduced locomotion, we could dissociate the effects of LPS on extinction and locomotion by using a lower dose of LPS (50 μg/kg) which impaired locomotion without affecting extinction. In addition, 15 hrs after an injection of 250 μg/kg LPS in adult rats, extinction learning and recall were impaired without affecting locomotion. A sub-chronic treatment with candesartan, an angiotensin II type 1 receptor blocker, prevented the LPS-induced impairment of extinction in adult rats. Our results demonstrate that activation of the innate immune system can disrupt auditory fear extinction in adolescent and adult animals. These findings also provide direction for clinical studies of novel treatments that modulate the innate immune system for stress-related disorders like PTSD. PMID:26520214

  6. Candesartan ameliorates impaired fear extinction induced by innate immune activation.

    PubMed

    Quiñones, María M; Maldonado, Lizette; Velazquez, Bethzaly; Porter, James T

    2016-02-01

    Patients with post-traumatic stress disorder (PTSD) tend to show signs of a relatively increased inflammatory state suggesting that activation of the immune system may contribute to the development of PTSD. In the present study, we tested whether activation of the innate immune system can disrupt acquisition or recall of auditory fear extinction using an animal model of PTSD. Male adolescent rats received auditory fear conditioning in context A. The next day, an intraperitoneal injection of lipopolysaccharide (LPS; 100 μg/kg) prior to auditory fear extinction in context B impaired acquisition and recall of extinction. LPS (100 μg/kg) given after extinction training did not impair extinction recall suggesting that LPS did not affect consolidation of extinction. In contrast to cued fear extinction, contextual fear extinction was not affected by prior injection of LPS (100 μg/kg). Although LPS also reduced locomotion, we could dissociate the effects of LPS on extinction and locomotion by using a lower dose of LPS (50 μg/kg) which impaired locomotion without affecting extinction. In addition, 15 h after an injection of 250 μg/kg LPS in adult rats, extinction learning and recall were impaired without affecting locomotion. A sub-chronic treatment with candesartan, an angiotensin II type 1 receptor blocker, prevented the LPS-induced impairment of extinction in adult rats. Our results demonstrate that activation of the innate immune system can disrupt auditory fear extinction in adolescent and adult animals. These findings also provide direction for clinical studies of novel treatments that modulate the innate immune system for stress-related disorders like PTSD.

  7. Antiamnesic Effect of Broccoli (Brassica oleracea var. italica) Leaves on Amyloid Beta (Aβ)1-42-Induced Learning and Memory Impairment.

    PubMed

    Park, Seon Kyeong; Ha, Jeong Su; Kim, Jong Min; Kang, Jin Yong; Lee, Du Sang; Guo, Tian Jiao; Lee, Uk; Kim, Dae-Ok; Heo, Ho Jin

    2016-05-04

    To examine the antiamnesic effects of broccoli (Brassica oleracea var. italica) leaves, we performed in vitro and in vivo tests on amyloid beta (Aβ)-induced neurotoxicity. The chloroform fraction from broccoli leaves (CBL) showed a remarkable neuronal cell-protective effect and an inhibition against acetylcholinesterase (AChE). The ameliorating effect of CBL on Aβ1-42-induced learning and memory impairment was evaluated by Y-maze, passive avoidance, and Morris water maze tests. The results indicated improving cognitive function in the CBL group. After the behavioral tests, antioxidant effects were detected by superoxide dismutase (SOD), oxidized glutathione (GSH)/total GSH, and malondialdehyde (MDA) assays, and inhibition against AChE was also presented in the brain. Finally, oxo-dihydroxy-octadecenoic acid (oxo-DHODE) and trihydroxy-octadecenoic acid (THODE) as main compounds were identified by quadrupole time-of-flight ultraperformance liquid chromatography (Q-TOF UPLC-MS) analysis. Therefore, our studies suggest that CBL could be used as a natural resource for ameliorating Aβ1-42-induced learning and memory impairment.

  8. Differential Regulation of Glutamic Acid Decarboxylase Gene Expression after Extinction of a Recent Memory vs. Intermediate Memory

    ERIC Educational Resources Information Center

    Sangha, Susan; Ilenseer, Jasmin; Sosulina, Ludmila; Lesting, Jorg; Pape, Hans-Christian

    2012-01-01

    Extinction reduces fear to stimuli that were once associated with an aversive event by no longer coupling the stimulus with the aversive event. Extinction learning is supported by a network comprising the amygdala, hippocampus, and prefrontal cortex. Previous studies implicate a critical role of GABA in extinction learning, specifically the GAD65…

  9. Differential Regulation of Glutamic Acid Decarboxylase Gene Expression after Extinction of a Recent Memory vs. Intermediate Memory

    ERIC Educational Resources Information Center

    Sangha, Susan; Ilenseer, Jasmin; Sosulina, Ludmila; Lesting, Jorg; Pape, Hans-Christian

    2012-01-01

    Extinction reduces fear to stimuli that were once associated with an aversive event by no longer coupling the stimulus with the aversive event. Extinction learning is supported by a network comprising the amygdala, hippocampus, and prefrontal cortex. Previous studies implicate a critical role of GABA in extinction learning, specifically the GAD65…

  10. Extinction of chained instrumental behaviors: Effects of procurement extinction on consumption responding.

    PubMed

    Thrailkill, Eric A; Bouton, Mark E

    2015-07-01

    Instrumental behavior often consists of sequences or chains of responses that minimally include procurement behaviors that enable subsequent consumption behaviors. In such chains, behavioral units are linked by access to one another and eventually to a primary reinforcer, such as food or a drug. The present experiments examined the effects of extinguishing procurement responding on consumption responding after training of a discriminated heterogeneous instrumental chain. Rats learned to make a procurement response (e.g., pressing a lever) in the presence of a distinctive discriminative stimulus; making that response led to the presentation of a second discriminative stimulus that set the occasion for a consumption response (e.g., pulling a chain), which then produced a food-pellet reinforcer. Experiment 1 showed that extinction of either the full procurement-consumption chain or procurement alone weakened the consumption response tested in isolation. Experiment 2 replicated the procurement extinction effect and further demonstrated that the opportunity to make the procurement response, as opposed to simple exposure to the procurement stimulus alone, was required. In Experiment 3, rats learned 2 distinct discriminated heterogeneous chains; extinction of 1 procurement response specifically weakened the consumption response that had been associated with it. The results suggest that learning to inhibit the procurement response may produce extinction of consumption responding through mediated extinction. The experiments suggest the importance of an associative analysis of instrumental behavior chains. (PsycINFO Database Record

  11. Extinction of Chained Instrumental Behaviors: Effects of Procurement Extinction on Consumption Responding

    PubMed Central

    Thrailkill, Eric A.; Bouton, Mark E.

    2015-01-01

    Instrumental behavior often consists of sequences or chains of responses that minimally include procurement behaviors that enable subsequent consumption behaviors. In such chains, behavioral units are linked by access to one another and eventually to a primary reinforcer, such as food or a drug. The present experiments examined the effects of extinguishing procurement responding on consumption responding after training of a discriminated heterogeneous instrumental chain. Rats learned to make a procurement response (e.g., pressing a lever) in the presence of a distinctive discriminative stimulus; making that response led to the presentation of a second discriminative stimulus that set the occasion for a consumption response (e.g., pulling a chain), which then produced a food-pellet reinforcer. Experiment 1 showed that extinction of either the full procurement-consumption chain or procurement alone weakened the consumption response tested in isolation. Experiment 2 replicated the procurement extinction effect and further demonstrated that the opportunity to make the procurement response, as opposed to simple exposure to the procurement stimulus alone, was required. In Experiment 3, rats learned 2 distinct discriminated heterogeneous chains; extinction of 1 procurement response specifically weakened the consumption response that had been associated with it. The results suggest that learning to inhibit the procurement response may produce extinction of consumption responding through mediated extinction. The experiments suggest the importance of an associative analysis of instrumental behavior chains. PMID:25915751

  12. Acute stress impairs the retrieval of extinction memory in humans

    PubMed Central

    Raio, Candace M.; Brignoni-Perez, Edith; Goldman, Rachel; Phelps, Elizabeth A.

    2014-01-01

    Extinction training is a form of inhibitory learning that allows an organism to associate a previously aversive cue with a new, safe outcome. Extinction does not erase a fear association, but instead creates a competing association that may or may not be retrieved when a cue is subsequently encountered. Characterizing the conditions under which extinction learning is expressed is important to enhancing the treatment of anxiety disorders that rely on extinction-based exposure therapy as a primary treatment technique. The ventromedial prefrontal cortex, which plays an important role in the expression of extinction memory, has been shown to be functionally impaired after stress exposure. Further, recent research in rodents found that exposure to stress led to deficits in extinction retrieval, although this has yet to be tested in humans. To explore how stress might influence extinction retrieval in humans, participants underwent a differential aversive learning paradigm, in which one image was probabilistically paired with an aversive shock while the other image denoted safety. Extinction training directly followed, at which point reinforcement was omitted. A day later, participants returned to the lab and either completed an acute stress manipulation (i.e., cold pressor), or a control task, before undergoing an extinction retrieval test. Skin conductance responses and salivary cortisol concentrations were measured throughout each session as indices of fear arousal and neuroendocrine stress responses, respectively. The efficacy of our stress induction was established by observing significant increases in cortisol for the stress condition only. We examined extinction retrieval by comparing conditioned responses during the last trial of extinction (day 1) with that of the first trial of re-extinction (day 2). Groups did not differ on initial fear acquisition or extinction, however, one day later participants in the stress group (n = 27) demonstrated significantly less

  13. The expression of c-Fos and colocalisation of c-Fos and glucocorticoid receptors in brain structures of low and high anxiety rats subjected to extinction trials and re-learning of a conditioned fear response.

    PubMed

    Lehner, Małgorzata; Wisłowska-Stanek, Aleksandra; Taracha, Ewa; Maciejak, Piotr; Szyndler, Janusz; Skórzewska, Anna; Turzyńska, Danuta; Sobolewska, Alicja; Hamed, Adam; Bidziński, Andrzej; Płaźnik, Adam

    2009-11-01

    We designed an animal model to examine the mechanisms of differences in individual responses to aversive stimuli. We used the rat freezing response in the context fear test as a discriminating variable: low responders (LR) were defined as rats with a duration of freezing response one standard error or more below the mean value, and high responders (HR) were defined as rats with a duration of freezing response one standard error or more above the mean value. We sought to determine the colocalisation of c-Fos and glucocorticoid receptors-immunoreactivity (GR-ir) in HR and LR rats subjected to conditioned fear training, two extinction sessions and re-learning of a conditioned fear. We found that HR animals showed a marked decrease in conditioned fear in the course of two extinction sessions (16 days) in comparison with the control and LR groups. The LR group exhibited higher activity in the cortical M2 and prelimbic areas (c-Fos) and had an increased number of cells co-expressing c-Fos and GR-ir in the M2 and medial orbital cortex after re-learning a contextual fear. HR rats showed increased expression of c-Fos, GR-ir and c-Fos/GR-ir colocalised neurons in the basolateral amygdala and enhanced c-Fos and GR-ir in the dentate gyrus (DG) in comparison with LR animals. Our data indicate that recovery of a context-related behaviour upon re-learning of contextual fear is accompanied in HR animals by a selective increase in c-Fos expression and GRs-ir in the DG area of the hippocampus.

  14. Extinction and spontaneous recovery of spatial behavior in pigeons

    PubMed Central

    Leising, Kenneth J.; Wong, Jared; Blaisdell, Aaron P.

    2015-01-01

    We investigated extinction and spontaneous recovery of spatial associations using a landmark-based appetitive search task in a touchscreen preparation with pigeons. Four visual landmarks (A, B, C, and D) were separately established as signals of a hidden reinforced target among an 8×7 array of potential target locations. The target was located above Landmarks A and C and below B and D. After conditioning, A and B were extinguished. Responding to A and C was assessed on probe tests 2 days following extinction, whereas, B and D were tested 14 days after extinction. We observed spontaneous recovery from spatial extinction following a 14-day, but not a 2-day, post-extinction retention interval. Furthermore, by plotting the spatial distribution of responding across the X and Y-axes during testing, we found that spontaneous recovery of responding to the target in our task was due to enhanced spatial control (i.e., a change in the overall distribution of responses) following the long delay to testing. These results add spatial extinction and spontaneous recovery to the list of findings supporting the assertion that extinction involves new learning that attenuates the originally acquired response, and that original learning of the spatial relationship between paired events survives extinction. PMID:26437383

  15. The role of the medial prefrontal cortex in trace fear extinction.

    PubMed

    Kwapis, Janine L; Jarome, Timothy J; Helmstetter, Fred J

    2014-01-01

    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 circuit than delay extinction; trace extinction requires the participation of the retrosplenial cortex, but not the amygdala, as noted in a previous study. Here, we tested the roles of the prelimbic and infralimbic regions of the medial prefrontal cortex in trace and delay fear extinction by blocking NMDA receptors during extinction learning. We found that the prelimbic cortex is necessary for trace, but not for delay fear extinction, whereas the infralimbic cortex is involved in both types of extinction. These results are consistent with the idea that trace fear associations require plasticity in multiple cortical areas for successful extinction. Further, the infralimbic cortex appears to play a role in extinction regardless of whether the animal was initially trained in trace or delay conditioning. Together, our results provide new information about how the neural circuits supporting trace and delay fear extinction differ.

  16. The role of the medial prefrontal cortex in trace fear extinction

    PubMed Central

    Kwapis, Janine L.; Jarome, Timothy J.

    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 circuit than delay extinction; trace extinction requires the participation of the retrosplenial cortex, but not the amygdala, as noted in a previous study. Here, we tested the roles of the prelimbic and infralimbic regions of the medial prefrontal cortex in trace and delay fear extinction by blocking NMDA receptors during extinction learning. We found that the prelimbic cortex is necessary for trace, but not for delay fear extinction, whereas the infralimbic cortex is involved in both types of extinction. These results are consistent with the idea that trace fear associations require plasticity in multiple cortical areas for successful extinction. Further, the infralimbic cortex appears to play a role in extinction regardless of whether the animal was initially trained in trace or delay conditioning. Together, our results provide new information about how the neural circuits supporting trace and delay fear extinction differ. PMID:25512576

  17. Biological extinction in earth history

    NASA Technical Reports Server (NTRS)

    Raup, D. M.

    1986-01-01

    Virtually all plant and animal species that have ever lived on the earth are extinct. For this reason alone, extinction must play an important role in the evolution of life. The five largest mass extinctions of the past 600 million years are of greatest interest, but there is also a spectrum of smaller events, many of which indicate biological systems in profound stress. Extinction may be episodic at all scales, with relatively long periods of stability alternating with short-lived extinction events. Most extinction episodes are biologically selective, and further analysis of the victims and survivors offers the greatest chance of deducing the proximal causes of extinction. A drop in sea level and climatic change are most frequently invoked to explain mass extinctions, but new theories of collisions with extraterrestrial bodies are gaining favor. Extinction may be constructive in a Darwinian sense or it may only perturb the system by eliminating those organisms that happen to be susceptible to geologically rare stresses.

  18. Biological extinction in earth history

    NASA Technical Reports Server (NTRS)

    Raup, D. M.

    1986-01-01

    Virtually all plant and animal species that have ever lived on the earth are extinct. For this reason alone, extinction must play an important role in the evolution of life. The five largest mass extinctions of the past 600 million years are of greatest interest, but there is also a spectrum of smaller events, many of which indicate biological systems in profound stress. Extinction may be episodic at all scales, with relatively long periods of stability alternating with short-lived extinction events. Most extinction episodes are biologically selective, and further analysis of the victims and survivors offers the greatest chance of deducing the proximal causes of extinction. A drop in sea level and climatic change are most frequently invoked to explain mass extinctions, but new theories of collisions with extraterrestrial bodies are gaining favor. Extinction may be constructive in a Darwinian sense or it may only perturb the system by eliminating those organisms that happen to be susceptible to geologically rare stresses.

  19. Biological extinction in earth history.

    PubMed

    Raup, D M

    1986-03-28

    Virtually all plant and animal species that have ever lived on the earth are extinct. For this reason alone, extinction must play an important role in the evolution of life. The five largest mass extinctions of the past 600 million years are of greatest interest, but there is also a spectrum of smaller events, many of which indicate biological systems in profound stress. Extinction may be episodic at all scales, with relatively long periods of stability alternating with short-lived extinction events. Most extinction episodes are biologically selective, and further analysis of the victims and survivors offers the greatest chance of deducing the proximal causes of extinction. A drop in sea level and climatic change are most frequently invoked to explain mass extinctions, but new theories of collisions with extraterrestrial bodies are gaining favor. Extinction may be constructive in a Darwinian sense or it may only perturb the system by eliminating those organisms that happen to be susceptible to geologically rare stresses.

  20. Requirement for BDNF in the reconsolidation of fear extinction.

    PubMed

    Radiske, Andressa; Rossato, Janine I; Köhler, Cristiano A; Gonzalez, Maria Carolina; Medina, Jorge H; Cammarota, Martín

    2015-04-22

    Therapies based on the impairment of reconsolidation or the enhancement of extinction offer the possibility of decreasing the persistent recollection of distressing memories. However, the direct interplay between reconsolidation and extinction has rarely been considered. Previously, we reported that reactivation induces reconsolidation of fear extinction memory. Here, using a step-down inhibitory avoidance learning paradigm in rats, we show that intrahippocampus infusion of function-blocking anti-BDNF antibody immediately or 6 h after extinction memory reactivation impairs the reconsolidation of extinction. Extinction memory reactivation increases proBDNF, BDNF, and tropomyosin receptor kinase B (TrkB) phosphorylation levels in dorsal CA1, while blocking BDNF maturation in the hippocampus with plasminogen activator inhibitor 1 hinders the persistence of extinction and induces the recurrence of fear. Moreover, coinfusion of recombinant BDNF (0.25 μg/side) after extinction memory reactivation impedes the recovery of the avoidance response induced by inhibiting gene expression and protein synthesis in the dorsal hippocampus. Our findings unravel a new role for BDNF, suggesting that this neurotrophin is necessary and sufficient to maintain the reactivated fear extinction engram.

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

    PubMed

    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

  2. Species extinction mires ecosystem

    SciTech Connect

    Holzman, D.

    1990-03-26

    Extinction is normal in the evolution of life, but amphibians, insects, birds and mammals are vanishing at an alarming pace. While habitat destruction, overexploitation and pollution are among the main causes, some disappearances cannot be explained. The extinction problem among amphibians mirrors the general, worldwide phenomenon. A synergism of insults may be responsible. Chance events such as a dry year might occasionally clean out a pond. But a larger lake nearby would replenish it. Now acid pollution adds to the ponds' burden while stocking of amphibian-eating sport fish in the lake - which happens even in natural parks - would destroy the source of replenishment. Some fear that extinctions ultimately could destroy nature's fabric.

  3. Cholinergic blockade frees fear extinction from its contextual dependency

    PubMed Central

    Zelikowsky, Moriel; Hast, Timothy A.; Bennett, Rebecca Z.; Merjanian, Michael; Nocera, Nathaniel A.; Ponnusamy, Ravikumar; Fanselow, Michael S.

    2012-01-01

    Background Fears that are maladaptive or inappropriate can be reduced through extinction training. However, extinction is highly context-sensitive, resulting in the renewal of fear following shifts in context, and limiting the clinical efficacy of extinction training. Lesion and inactivation studies have shown that the contextualization of extinction depends on the hippocampus. Parallel studies have found that intrahippocampal scopolamine blocks contextual fear conditioning. Importantly, this effect was replicated using a non-invasive technique in which a low dose of scopolamine was administered systemically. We aimed to transfer the effects of this non-invasive approach to block the contextualization of fear extinction. Methods Rats were tone fear conditioned and extinguished under various systemic doses of scopolamine or the saline vehicle. They were subsequently tested (off drug) for tone fear in a context that was the same (controls) or shifted (renewal group) with respect to the extinction context. Results The lowest dose of scopolamine produced a significant attenuation of fear renewal when renewal was tested either in the original training context or a novel context. The drug also slowed the rate of long-term extinction memory formation, which was readily overcome by extending extinction training. Scopolamine only gave this effect when it was administered during, but not after extinction training. Higher doses of scopolamine severely disrupted extinction learning. Conclusions We discovered that disrupting contextual processing during extinction with the cholinergic antagonist scopolamine blocked subsequent fear renewal. Low doses of scopolamine may be a clinically promising adjunct to exposure therapy by making extinction more relapse-resistant. PMID:22981655

  4. Supernovae and mass extinctions

    NASA Technical Reports Server (NTRS)

    Vandenbergh, S.

    1994-01-01

    Shklovsky and others have suggested that some of the major extinctions in the geological record might have been triggered by explosions of nearby supernovae. The frequency of such extinction events will depend on the galactic supernova frequency and on the distance up to which a supernova explosion will produce lethal effects upon terrestrial life. In the present note it will be assumed that a killer supernova has to occur so close to Earth that it will be embedded in a young, active, supernova remnant. Such young remnants typically have radii approximately less than 3 pc (1 x 10(exp 19) cm). Larger (more pessimistic?) killer radii have been adopted by Ruderman, Romig, and by Ellis and Schramm. From observations of historical supernovae, van den Bergh finds that core-collapse (types Ib and II) supernovae occur within 4 kpc of the Sun at a rate of 0.2 plus or minus 0.1 per century. Adopting a layer thickness of 0.3 kpc for the galacitc disk, this corresponds to a rate of approximately 1.3 x 10(exp -4) supernovae pc(exp -3) g.y.(exp -1). Including supernovae of type Ia will increase the total supernovae rate to approximately 1.5 x 10(exp -4) supernovae pc(exp -3) g.y.(exp -1). For a lethal radius of R pc the rate of killer events will therefore be 1.7 (R/3)(exp 3) x 10(exp -2) supernovae per g.y. However, a frequency of a few extinctions per g.y. is required to account for the extinctions observed during the phanerozoic. With R (extinction) approximately 3 pc, the galactic supernova frequency is therefore too low by 2 orders of magnitude to account for the major extinctions in the geological record.

  5. Single nanowire extinction spectroscopy.

    PubMed

    Giblin, Jay; Vietmeyer, Felix; McDonald, Matthew P; Kuno, Masaru

    2011-08-10

    Here we show the first direct extinction spectra of single one-dimensional (1D) semiconductor nanostructures obtained at room temperature utilizing a spatial modulation approach. (1) For these materials, ensemble averaging in conventional extinction spectroscopy has limited our understanding of the interplay between carrier confinement and their electrostatic interactions. (2-4) By probing individual CdSe nanowires (NWs), we have identified and assigned size-dependent exciton transitions occurring across the visible. In turn, we have revealed the existence of room temperature 1D excitons in the narrowest NWs.

  6. Delayed recall of fear extinction in rats with lesions of ventral medial prefrontal cortex.

    PubMed

    Lebrón, 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 rats were unable to retrieve extinction memory stored in other structures. To determine if a latent extinction memory could be retrieved with additional training, we repeated the experiment but added an additional 5 d of extinction reminder trials. Replicating our previous findings, vmPFC-lesioned rats extinguished normally on day 1, but showed no recall of extinction on day 2. Over the next 5 d, however, lesioned rats showed significant savings in their rate of re-extinction. Thus, the vmPFC is not the only site where extinction memory is stored. Nevertheless, lesioned rats receiving only two extinction trials per day required twice as many days to initiate extinction as controls. Although recall of extinction is possible without the vmPFC, it is significantly delayed. We suggest that the vmPFC accelerates extinction by permitting access to recently learned extinction trials, thereby maximizing behavioral flexibility.

  7. Extinction from a paleontological perspective

    NASA Technical Reports Server (NTRS)

    Raup, D. M.

    1993-01-01

    Extinction of widespread species is common in evolutionary time (millions of years) but rare in ecological time (hundreds or thousands of years). In the fossil record, there appears to be a smooth continuum between background and mass extinction; and the clustering of extinctions at mass extinctions cannot be explained by the chance coincidence of independent events. Although some extinction is selective, much is apparently random in that survivors have no recognizable superiority over victims. Extinction certainly plays an important role in evolution, but whether it is constructive or destructive has not yet been determined.

  8. Extinction from a paleontological perspective

    NASA Technical Reports Server (NTRS)

    Raup, D. M.

    1993-01-01

    Extinction of widespread species is common in evolutionary time (millions of years) but rare in ecological time (hundreds or thousands of years). In the fossil record, there appears to be a smooth continuum between background and mass extinction; and the clustering of extinctions at mass extinctions cannot be explained by the chance coincidence of independent events. Although some extinction is selective, much is apparently random in that survivors have no recognizable superiority over victims. Extinction certainly plays an important role in evolution, but whether it is constructive or destructive has not yet been determined.

  9. Extinction from a paleontological perspective.

    PubMed

    Raup, D M

    1993-01-01

    Extinction of widespread species is common in evolutionary time (millions of years) but rare in ecological time (hundreds or thousands of years). In the fossil record, there appears to be a smooth continuum between background and mass extinction; and the clustering of extinctions at mass extinctions cannot be explained by the chance coincidence of independent events. Although some extinction is selective, much is apparently random in that survivors have no recognizable superiority over victims. Extinction certainly plays an important role in evolution, but whether it is constructive or destructive has not yet been determined.

  10. Extinction and Renewal of Conditioned Sexual Responses

    PubMed Central

    Brom, Mirte; Laan, Ellen; Everaerd, Walter; Spinhoven, Philip; Both, Stephanie

    2014-01-01

    Introduction Extinction involves an inhibitory form of new learning that is highly dependent on the context for expression. This is supported by phenomena such as renewal and spontaneous recovery, which may help explain the persistence of appetitive behavior, and related problems such as addictions. Research on these phenomena in the sexual domain is lacking, where it may help to explain the persistence of learned sexual responses. Method Men (n = 40) and women (n = 62) participated in a differential conditioning paradigm, with genital vibrotactile stimulation as US and neutral pictures as conditional stimuli (CSs). Dependent variables were genital and subjective sexual arousal, affect, US expectancy, and approach and avoid tendencies towards the CSs. Extinction and renewal of conditioned sexual responses were studied by context manipulation (AAA vs. ABA condition). Results No renewal effect of genital conditioned responding could be detected, but an obvious recovery of US expectancy following a context change after extinction (ABA) was demonstrated. Additionally, women demonstrated recovery of subjective affect and subjective sexual arousal. Participants in the ABA demonstrated more approach biases towards stimuli. Conclusions The findings support the context dependency of extinction and renewal of conditioned sexual responses in humans. This knowledge may have implications for the treatment of disturbances in sexual appetitive responses such as hypo- and hypersexuality. PMID:25170909

  11. Intolerance of uncertainty predicts fear extinction in amygdala-ventromedial prefrontal cortical circuitry.

    PubMed

    Morriss, Jayne; Christakou, Anastasia; van Reekum, Carien M

    2015-01-01

    Coordination of activity between the amygdala and ventromedial prefrontal cortex (vmPFC) is important for fear-extinction learning. Aberrant recruitment of this circuitry is associated with anxiety disorders. Here, we sought to determine if individual differences in future threat uncertainty sensitivity, a potential risk factor for anxiety disorders, underly compromised recruitment of fear extinction circuitry. Twenty-two healthy subjects completed a cued fear conditioning task with acquisition and extinction phases. During the task, pupil dilation, skin conductance response, and functional magnetic resonance imaging were acquired. We assessed the temporality of fear extinction learning by splitting the extinction phase into early and late extinction. Threat uncertainty sensitivity was measured using self-reported intolerance of uncertainty (IU). During early extinction learning, we found low IU scores to be associated with larger skin conductance responses and right amygdala activity to learned threat vs. safety cues, whereas high IU scores were associated with no skin conductance discrimination and greater activity within the right amygdala to previously learned safety cues. In late extinction learning, low IU scores were associated with successful inhibition of previously learned threat, reflected in comparable skin conductance response and right amgydala activity to learned threat vs. safety cues, whilst high IU scores were associated with continued fear expression to learned threat, indexed by larger skin conductance and amygdala activity to threat vs. safety cues. In addition, high IU scores were associated with greater vmPFC activity to threat vs. safety cues in late extinction. Similar patterns of IU and extinction learning were found for pupil dilation. The results were specific for IU and did not generalize to self-reported trait anxiety. Overall, the neural and psychophysiological patterns observed here suggest high IU individuals to disproportionately

  12. The role of the amygdala in the extinction of conditioned fear.

    PubMed

    Barad, Mark; Gean, Po-Wu; Lutz, Beat

    2006-08-15

    The amygdala has long been known to play a central role in the acquisition and expression of fear. More recently, convergent evidence has implicated the amygdala in the extinction of fear as well. In rodents, some of this evidence comes from the infusion of drugs directly into the amygdala and, in particular, into the basolateral complex of the amygdala, during or after extinction learning. In vivo electrophysiology has identified cellular correlates of extinction learning and memory in the lateral nucleus of that structure. Human imaging experiments also indicate that amygdaloid activity correlates with extinction training. In addition, some studies have directly identified changes in molecular constituents of the basolateral amygdala. Together these experiments strongly indicate that the basolateral amygdala plays a crucial role in extinction learning. Interpreted in the light of these findings, several recent in vitro electrophysiology studies in amygdala-containing brain slices are suggestive of potential synaptic and circuit bases of extinction learning.

  13. CME leaving the Sun [Video

    NASA Image and Video Library

    2017-09-27

    Animation of a CME leaving the Sun, slamming into our magnetosphere. Credit: NASA/GSFC/SOHO/ESA Sound: Juan Carlos Garcia To learn more go to the SOHO website: sohowww.nascom.nasa.gov/home.html To learn more about NASA's Sun Earth Day go here: sunearthday.nasa.gov/2010/index.php

  14. Unexpectedly many extinct hominins.

    PubMed

    Bokma, Folmer; van den Brink, Valentijn; Stadler, Tanja

    2012-09-01

    Recent studies indicate that Neanderthal and Denisova hominins may have been separate species, while debate continues on the status of Homo floresiensis. The decade-long debate between "splitters," who recognize over 20 hominin species, and "lumpers," who maintain that all these fossils belong to just a few lineages, illustrates that we do not know how many extinct hominin species to expect. Here, we present probability distributions for the number of speciation events and the number of contemporary species along a branch of a phylogeny. With estimates of hominin speciation and extincton rates, we then show that the expected total number of extinct hominin species is 8, but may be as high as 27. We also show that it is highly unlikely that three very recent species disappeared due to natural, background extinction. This may indicate that human-like remains are too easily considered distinct species. Otherwise, the evidence suggesting that Neanderthal and the Denisova hominin represent distinct species implies a recent wave of extinctions, ostensibly driven by the only survivor, H. sapiens. © 2012 The Author(s). Evolution© 2012 The Society for the Study of Evolution.

  15. Extinction in population dynamics

    NASA Astrophysics Data System (ADS)

    Escudero, C.; Buceta, J.; de La Rubia, F. J.; Lindenberg, Katja

    2004-02-01

    We study a generic reaction-diffusion model for single-species population dynamics that includes reproduction, death, and competition. The population is assumed to be confined in a refuge beyond which conditions are so harsh that they lead to certain extinction. Standard continuum mean field models in one dimension yield a critical refuge length Lc such that a population in a refuge larger than this is assured survival. Herein we extend the model to take into account the discreteness and finiteness of the population, which leads us to a stochastic description. We present a particular critical criterion for likely extinction, namely, that the standard deviation of the population be equal to the mean. According to this criterion, we find that while survival can no longer be guaranteed for any refuge size, for sufficiently weak competition one can make the refuge large enough (certainly larger than Lc) to cause extinction to be unlikely. However, beyond a certain value of the competition rate parameter it is no longer possible to escape a likelihood of extinction even in an infinite refuge. These unavoidable fluctuations therefore have a severe impact on refuge design issues.

  16. Biogeography and extinction

    SciTech Connect

    Jablonski, D.

    1985-01-01

    The geographic ranges of species and clades, and the deployment of those clades among biogeographic provinces, are important determinants of rates and patterns of extinction. Studies of Late Cretaceous mollusks of the Gulf and Atlantic Coastal Plain confirm that species duration is closely correlated with geographic range during times of normal, background extinction. When species that originate in the last 2 myr of the Cretaceous, the correlation increases significantly. The fact that even these truncated species frequently attained broad geographic ranges indicates that during background times duration is a function of geographic range and not vice versa. However, during the end-Cretaceous mass extinction, it is clade geographic range and not the within-province ranges of its constituent species that determines survivorship: about 55% of the widespread genera but only 12% of the endemic genera survive, regardless of the ranges of their individual species. Thus, clade geographic range is an irreducible property, with effects decoupled from species-level or organismic traits that determine species' geographic ranges. Clades with tropical distributions suffer disproportionately, again independent of species' geographic range magnitudes. Survivorship of taxa or morphologies during mass extinctions may have little to do with adaptation at the organismic or even species level, but depends at least in part on clade-level traits that are less important during background times.

  17. Raising the Leaving Learning Age: Are the Public Convinced? A Survey of Parents and Teenagers. Research Report

    ERIC Educational Resources Information Center

    Villeneuve-Smith, Frank; Marshall, Liz; Munoz, Silvia

    2007-01-01

    This research explores the attitudes of parents and teenagers towards the proposals in the "Raising expectations" Green Paper. It is based on a public opinion poll of 920 parents and 380 teenagers in the United Kingdom, which ran between 30 March and 10 April 2007. The results were analysed by Learning and Skills Network statisticians.…

  18. Leave It to Beaver. Merchants Millpond State Park: An Environmental Education Learning Experience Designed for Grades 4-6.

    ERIC Educational Resources Information Center

    Williams, Floyd K.

    This learning packet, one in a group of eight, was developed by the Merchants Millpond State Park in North Carolina to teach students in grades 4-6 about the habitat and lifestyle of the beaver. Loose-leaf pages are presented in nine sections that contain: (1) introductions to the North Carolina State Parks System, the Merchants Millpond State…

  19. Calcineurin inhibition blocks within-, but not between-session fear extinction in mice.

    PubMed

    Almeida-Corrêa, Suellen; Moulin, Thiago C; Carneiro, Clarissa F D; Gonçalves, Marina M C; Junqueira, Lara S; Amaral, Olavo B

    2015-03-01

    Memory extinction involves the formation of a new associative memory that inhibits a previously conditioned association. Nonetheless, it could also depend on weakening of the original memory trace if extinction is assumed to have multiple components. The phosphatase calcineurin (CaN) has been described as being involved in extinction but not in the initial consolidation of fear learning. With this in mind, we set to study whether CaN could have different roles in distinct components of extinction. Systemic treatment with the CaN inhibitors cyclosporin A (CsA) or FK-506, as well as i.c.v. administration of CsA, blocked within-session, but not between-session extinction or initial learning of contextual fear conditioning. Similar effects were found in multiple-session extinction of contextual fear conditioning and in auditory fear conditioning, indicating that CaN is involved in different types of short-term extinction. Meanwhile, inhibition of protein synthesis by cycloheximide (CHX) treatment did not affect within-session extinction, but disrupted fear acquisition and slightly impaired between-session extinction. Our results point to a dissociation of within- and between-session extinction of fear conditioning, with the former being more dependent on CaN activity and the latter on protein synthesis. Moreover, the modulation of within-session extinction did not affect between-session extinction, suggesting that these components are at least partially independent.

  20. Calcineurin inhibition blocks within-, but not between-session fear extinction in mice

    PubMed Central

    Moulin, Thiago C.; Carneiro, Clarissa F. D.; Gonçalves, Marina M. C.; Junqueira, Lara S.; Amaral, Olavo B.

    2015-01-01

    Memory extinction involves the formation of a new associative memory that inhibits a previously conditioned association. Nonetheless, it could also depend on weakening of the original memory trace if extinction is assumed to have multiple components. The phosphatase calcineurin (CaN) has been described as being involved in extinction but not in the initial consolidation of fear learning. With this in mind, we set to study whether CaN could have different roles in distinct components of extinction. Systemic treatment with the CaN inhibitors cyclosporin A (CsA) or FK-506, as well as i.c.v. administration of CsA, blocked within-session, but not between-session extinction or initial learning of contextual fear conditioning. Similar effects were found in multiple-session extinction of contextual fear conditioning and in auditory fear conditioning, indicating that CaN is involved in different types of short-term extinction. Meanwhile, inhibition of protein synthesis by cycloheximide (CHX) treatment did not affect within-session extinction, but disrupted fear acquisition and slightly impaired between-session extinction. Our results point to a dissociation of within- and between-session extinction of fear conditioning, with the former being more dependent on CaN activity and the latter on protein synthesis. Moreover, the modulation of within-session extinction did not affect between-session extinction, suggesting that these components are at least partially independent. PMID:25691516

  1. Mass Extinctions Past and Present.

    ERIC Educational Resources Information Center

    Allmon, Warren Douglas

    1987-01-01

    Discusses some parallels that seem to exist between mass extinction recognizable in the geologic record and the impending extinction of a significant proportion of the earth's species due largely to tropical deforestation. Describes some recent theories of causal factors and periodicities in mass extinction. (Author/TW)

  2. Mass Extinctions Past and Present.

    ERIC Educational Resources Information Center

    Allmon, Warren Douglas

    1987-01-01

    Discusses some parallels that seem to exist between mass extinction recognizable in the geologic record and the impending extinction of a significant proportion of the earth's species due largely to tropical deforestation. Describes some recent theories of causal factors and periodicities in mass extinction. (Author/TW)

  3. Inactivation of the Infralimbic but Not the Prelimbic Cortex Impairs Consolidation and Retrieval of Fear Extinction

    ERIC Educational Resources Information Center

    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…

  4. Inactivation of the Infralimbic but Not the Prelimbic Cortex Impairs Consolidation and Retrieval of Fear Extinction

    ERIC Educational Resources Information Center

    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…

  5. Differential Endocannabinoid Regulation of Extinction in Appetitive and Aversive Barnes Maze Tasks

    ERIC Educational Resources Information Center

    Harloe, John P.; Thorpe, Andrew J.; Lichtman, Aron H.

    2008-01-01

    CB[subscript 1] receptor-compromised animals show profound deficits in extinguishing learned behavior from aversive conditioning tasks, but display normal extinction learning in appetitive operant tasks. However, it is difficult to discern whether the differential involvement of the endogenous cannabinoid system on extinction results from the…

  6. Differential Endocannabinoid Regulation of Extinction in Appetitive and Aversive Barnes Maze Tasks

    ERIC Educational Resources Information Center

    Harloe, John P.; Thorpe, Andrew J.; Lichtman, Aron H.

    2008-01-01

    CB[subscript 1] receptor-compromised animals show profound deficits in extinguishing learned behavior from aversive conditioning tasks, but display normal extinction learning in appetitive operant tasks. However, it is difficult to discern whether the differential involvement of the endogenous cannabinoid system on extinction results from the…

  7. Extinction of drug seeking: Neural circuits and approaches to augmentation.

    PubMed

    McNally, Gavan P

    2014-01-01

    Extinction training can reduce drug seeking behavior. This article reviews the neural circuits that contribute to extinction and approaches to enhancing the efficacy of extinction. Extinction of drug seeking depends on cortical-striatal-hypothalamic and cortical-hypothalamic-thalamic pathways. These pathways interface, in the hypothalamus and thalamus respectively, with the neural circuits controlling reinstatement of drug seeking. The actions of these pathways at lateral hypothalamic orexin neurons, and of perifornical/dorsomedial hypothalamic derived opioid peptides at kappa opioid receptors in the paraventricular thalamus, are important for inhibiting drug seeking. Despite effectively reducing or inhibiting drug seeking in the short term, extinguished drug seeking is prone to relapse. Three different strategies to augment extinction learning or retrieval are reviewed: pharmacological augmentation, retrieval - extinction training, and provision of extinction memory retrieval cues. These strategies have been used in animal models and with human drug users to enhance extinction or cue exposure treatments. They hold promise as novel strategies to promote abstinence from drug seeking. This article is part of a Special Issue entitled 'NIDA 40th Anniversary Issue'.

  8. HDAC3-selective inhibitor enhances extinction of cocaine-seeking behavior in a persistent manner.

    PubMed

    Malvaez, Melissa; McQuown, Susan C; Rogge, George A; Astarabadi, Mariam; Jacques, Vincent; Carreiro, Samantha; Rusche, James R; Wood, Marcelo A

    2013-02-12

    Nonspecific histone deacetylase (HDAC) inhibition has been shown to facilitate the extinction of drug-seeking behavior in a manner resistant to reinstatement. A key open question is which specific HDAC is involved in the extinction of drug-seeking behavior. Using the selective HDAC3 inhibitor RGFP966, we investigated the role of HDAC3 in extinction and found that systemic treatment with RGFP966 facilitates extinction in mice in a manner resistant to reinstatement. We also investigated whether the facilitated extinction is related to the enhancement of extinction consolidation during extinction learning or to negative effects on performance or reconsolidation. These are key distinctions with regard to any compound being used to modulate extinction, because a more rapid decrease in a defined behavior is interpreted as facilitated extinction. Using an innovative combination of behavioral paradigms, we found that a single treatment of RGFP966 enhances extinction of a previously established cocaine-conditioned place preference, while simultaneously enhancing long-term object-location memory within subjects. During extinction consolidation, HDAC3 inhibition promotes a distinct pattern of histone acetylation linked to gene expression within the infralimbic cortex, hippocampus, and nucleus accumbens. Thus, the facilitated extinction of drug-seeking cannot be explained by adverse effects on performance. These results demonstrate that HDAC3 inhibition enhances the memory processes involved in extinction of drug-seeking behavior.

  9. Extinction and spontaneous recovery of spatial behavior in pigeons.

    PubMed

    Leising, Kenneth J; Wong, Jared; Blaisdell, Aaron P

    2015-10-01

    We investigated extinction and spontaneous recovery of spatial associations using a landmark-based appetitive search task in a touchscreen preparation with pigeons. Four visual landmarks (A, B, C, and D) were separately established as signals of a hidden reinforced target among an 8 × 7 array of potential target locations. The target was located above landmarks (LM) A and C and below B and D. After conditioning, A and B were extinguished. Responding to A and C was assessed on probe tests 2 days following extinction, whereas, B and D were tested 14 days after extinction. We observed spontaneous recovery from spatial extinction following a 14-day, but not a 2-day, postextinction retention interval. Furthermore, by plotting the spatial distribution of responding across the X and Y axes during testing, we found that spontaneous recovery of responding to the target in our task was due to enhanced spatial control (i.e., a change in the overall distribution of responses) following the long delay to testing. These results add spatial extinction and spontaneous recovery to the list of findings supporting the assertion that extinction involves new learning that attenuates the originally acquired response, and that original learning of the spatial relationship between paired events survives extinction. (PsycINFO Database Record

  10. Habituation and extinction of fear recruit overlapping forebrain structures.

    PubMed

    Furlong, Teri M; Richardson, Rick; McNally, Gavan P

    2016-02-01

    Establishing the neurocircuitry involved in inhibiting fear is important for understanding and treating anxiety disorders. To date, extinction procedures have been predominately used to examine the inhibition of learned fear, where fear is reduced to a conditioned stimulus (CS) by presenting it in the absence of the unconditioned stimulus (US). However, learned fear can also be reduced by habituation procedures where the US is presented in the absence of the CS. Here we used expression of the activity marker c-Fos in rats to compare the recruitment of several forebrain structures following fear habituation and extinction. Following fear conditioning where a tone CS was paired with a loud noise US, fear was then reduced the following day by either presentation of the CS or US alone (i.e. CS extinction or US habituation, respectively). This extinction and habituation training recruited several common structures, including infralimbic cortex, basolateral amygdala, midline thalamus and medial hypothalamus (orexin neurons). Moreover, this overlap was shared when examining the neural correlates of the expression of habituation and extinction, with common recruitment of infralimbic cortex and midline thalamus. However, there were also important differences. Specifically, acquisition of habituation was associated with greater recruitment of prelimbic cortex whereas expression of habituation was associated with greater recruitment of paraventricular thalamus. There was also less recruitment of central amygdala for habituation compared to extinction in the retention phase. These findings indicate that largely overlapping neurocircuitries underlie habituation and fear extinction and imply common mechanisms for reducing fear across different inhibitory treatments.

  11. Pulsar extinction. [astrophysics

    NASA Technical Reports Server (NTRS)

    Sturrock, P. A.; Baker, K.; Turk, J. S.

    1975-01-01

    Radio emission from pulsars, attributed to an instability associated with the creation of electron-positron pairs from gamma rays was investigated. The condition for pair creation therefore lead to an extinction condition. The relevant physical processes were analyzed in the context of a mathematical model, according to which radiation originated at the polar caps and magnetic field lines changed from a closed configuration to an open configuration at the force balance or corotation radius.

  12. Stressor controllability modulates fear extinction in humans.

    PubMed

    Hartley, Catherine A; Gorun, Alyson; Reddan, Marianne C; Ramirez, Franchesca; Phelps, Elizabeth A

    2014-09-01

    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 randomly assigned to an escapable stressor condition, a yoked inescapable stressor condition, or a control condition involving no stress exposure. One week later, all participants underwent fear conditioning, fear extinction, and a test of extinction retrieval the following day. Participants exposed to inescapable stress showed impaired fear extinction learning and increased fear expression the following day. In contrast, escapable stress improved fear extinction and prevented the spontaneous recovery of fear. Consistent with the bidirectional controllability effects previously reported in animal models, these results suggest that one's degree of control over aversive experiences may be an important factor influencing the development of psychological resilience or vulnerability in humans.

  13. Stressor controllability modulates fear extinction in humans

    PubMed Central

    Hartley, Catherine A.; Gorun, Alyson; Reddan, Marianne C.; Ramirez, Franchesca; Phelps, Elizabeth A.

    2014-01-01

    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 randomly assigned to an escapable stressor condition, a yoked inescapable stressor condition, or a control condition involving no stress exposure. One week later, all participants underwent fear conditioning, fear extinction, and a test of extinction retrieval the following day. Participants exposed to inescapable stress showed impaired fear extinction learning and increased fear expression the following day. In contrast, escapable stress improved fear extinction and prevented the spontaneous recovery of fear. Consistent with the bidirectional controllability effects previously reported in animal models, these results suggest that one's degree of control over aversive experiences may be an important factor influencing the development of psychological resilience or vulnerability in humans. PMID:24333646

  14. Extinction in SC galaxies

    NASA Astrophysics Data System (ADS)

    Giovanelli, Riccardo; Haynes, Martha P.; Salzer, John J.; Wegner, Gary; da Costa, Luiz N.; Freudling, Wolfram

    1994-06-01

    We analyze the photometric properties of a sample of Sbc-Sc galaxies with known redshifts, single-dish H I profiles, and Charge Coupled Device (CCD) I band images. We derive laws that relate the measured isophotal radius at muI = 23.5, magnitude, scale length, and H I flux to the face-on aspect. We find spiral galaxies to be substantially less transparent than suggested in most previous determinations, but not as opaque as claimed by Valentijn (1990). Regions in the disk farther than two or three scale lengths from the center are close to completely transparent. In addition to statistically derived relations for the inclination dependence of photometric parameters, we present the results of a modeling exercise that utilizes the 'triplex' model of Disney et al. (1989) to obtain upper limits of the disk opacity. Within the framework of that model, and with qualitative consideration of the effects of scattering on extinction, we estimate late spiral disks at I band to have central optical depths tauI(0) less than 5 and dust absorbing layers with scale heights on the order of half that of the stellar component or less. We discuss our results in light of previous determinations of internal extinction relations and point out the substantial impact of internal extinction on the scatter of the Tully-Fisher relation. We also find that the visual diameters by which large catalogs are constructed (UGC, ESO-Uppsala) are nearly proportional to face-on isophotal diameters.

  15. 2-arachidonoylglycerol signaling impairs short-term fear extinction.

    PubMed

    Hartley, N D; Gunduz-Cinar, O; Halladay, L; Bukalo, O; Holmes, A; Patel, S

    2016-03-01

    Impairments in fear extinction are thought to be central to the psychopathology of posttraumatic stress disorder, and endocannabinoid (eCB) signaling has been strongly implicated in extinction learning. Here we utilized the monoacylglycerol lipase inhibitor JZL184 to selectively augment brain 2-AG levels combined with an auditory cue fear-conditioning paradigm to test the hypothesis that 2-AG-mediated eCB signaling modulates short-term fear extinction learning in mice. We show that systemic JZL184 impairs short-term extinction learning in a CB1 receptor-dependent manner without affecting non-specific freezing behavior or the acquisition of conditioned fear. This effect was also observed in over-conditioned mice environmentally manipulated to re-acquire fear extinction. Cumulatively, the effects of JZL184 appear to be partly due to augmentation of 2-AG signaling in the basolateral nucleus of the amygdala (BLA), as direct microinfusion of JZL184 into the BLA produced similar results. Moreover, we elucidate a short ~3-day temporal window during which 2-AG augmentation impairs extinction behavior, suggesting a preferential role for 2-AG-mediated eCB signaling in the modulation of short-term behavioral sequelae to acute traumatic stress exposure.

  16. 2-arachidonoylglycerol signaling impairs short-term fear extinction

    PubMed Central

    Hartley, N D; Gunduz-Cinar, O; Halladay, L; Bukalo, O; Holmes, A; Patel, S

    2016-01-01

    Impairments in fear extinction are thought to be central to the psychopathology of posttraumatic stress disorder, and endocannabinoid (eCB) signaling has been strongly implicated in extinction learning. Here we utilized the monoacylglycerol lipase inhibitor JZL184 to selectively augment brain 2-AG levels combined with an auditory cue fear-conditioning paradigm to test the hypothesis that 2-AG-mediated eCB signaling modulates short-term fear extinction learning in mice. We show that systemic JZL184 impairs short-term extinction learning in a CB1 receptor-dependent manner without affecting non-specific freezing behavior or the acquisition of conditioned fear. This effect was also observed in over-conditioned mice environmentally manipulated to re-acquire fear extinction. Cumulatively, the effects of JZL184 appear to be partly due to augmentation of 2-AG signaling in the basolateral nucleus of the amygdala (BLA), as direct microinfusion of JZL184 into the BLA produced similar results. Moreover, we elucidate a short ~3-day temporal window during which 2-AG augmentation impairs extinction behavior, suggesting a preferential role for 2-AG-mediated eCB signaling in the modulation of short-term behavioral sequelae to acute traumatic stress exposure. PMID:26926885

  17. Spontaneous recovery from extinction in the infant rat.

    PubMed

    Revillo, D A; Paglini, M G; Arias, C

    2014-11-01

    Within the Pavlovian conditioning framework, extinction is a procedure in which, after conditioning, the conditioned stimulus (CS) is repeatedly presented without the unconditioned stimulus (US). During this procedure the conditioned response (CR) is gradually attenuated. It has been suggested that extinction during the early stages of ontogeny is a qualitatively different process from extinction in adulthood: during infancy, extinction may result in erasure of the memory, while during adulthood extinction involves new learning. This conclusion was supported by studies showing that renewal, reinstatement or spontaneous recovery procedures were not effective during infancy for recovering the CR once it had been extinguished. These studies used the freezing response as the only behavioral index, although some recent evidence indicates that the absence of freezing after conditioning or after extinction does not necessarily imply a deficit in memory, and that other behavioral indexes may be more sensitive to detecting conditioning effects. The goal of the present study was to analyze extinction in preweanling rats by examining the possibility of the spontaneous recovery of a conditioned fear response, measured through a different set of mutually-exclusive behaviors that constitute an exhaustive ethogram, and including control groups (Experiment 1: US-Only and CS-Only; Experiment 2: US-Only, CS-Only and Unpaired) in order to examine whether non-associative learning may explain quantitative or qualitative changes in the frequency of specific responses during extinction or recovery. Extinction produced changes in the expression of freezing, grooming and exploration, and the clearest evidence of spontaneous recovery came from the analysis of freezing behavior. The pattern of behavior observed during extinction is compatible with theoretical approaches which consider different dynamic behavioral systems, and it also fit in well with a molar approach to the analysis of

  18. Contextual-Specificity of Short-Delay Extinction in Humans: Renewal of Fear-Potentiated Startle in a Virtual Environment

    ERIC Educational Resources Information Center

    Alvarez, Ruben P.; Johnson, Linda; Grillon, Christian

    2007-01-01

    A recent fear-potentiated startle study in rodents suggested that extinction was not context dependent when extinction was conducted after a short delay following acquisition, suggesting that extinction can lead to erasure of fear learning in some circumstances. The main objective of this study was to attempt to replicate these findings in humans…

  19. Contextual-Specificity of Short-Delay Extinction in Humans: Renewal of Fear-Potentiated Startle in a Virtual Environment

    ERIC Educational Resources Information Center

    Alvarez, Ruben P.; Johnson, Linda; Grillon, Christian

    2007-01-01

    A recent fear-potentiated startle study in rodents suggested that extinction was not context dependent when extinction was conducted after a short delay following acquisition, suggesting that extinction can lead to erasure of fear learning in some circumstances. The main objective of this study was to attempt to replicate these findings in humans…

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

    ERIC Educational Resources Information Center

    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,…

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

    ERIC Educational Resources Information Center

    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,…

  2. Yohimbine Impairs Extinction of Cocaine-Conditioned Place Preference in an [alpha] [subscript 2]-Adrenergic Receptor Independent Process

    ERIC Educational Resources Information Center

    Davis, Adeola R.; Shields, Angela D.; Brigman, Jonathan L.; Norcross, Maxine; McElligott, Zoe A.; Holmes, Andrew; Winder, Danny G.

    2008-01-01

    Extinction, a form of learning that has the ability to reshape learned behavior based on new experiences, has been heavily studied utilizing fear learning paradigms. Mechanisms underlying extinction of positive-valence associations, such as drug self-administration and place preference, are poorly understood yet may have important relevance to…

  3. Yohimbine Impairs Extinction of Cocaine-Conditioned Place Preference in an [alpha] [subscript 2]-Adrenergic Receptor Independent Process

    ERIC Educational Resources Information Center

    Davis, Adeola R.; Shields, Angela D.; Brigman, Jonathan L.; Norcross, Maxine; McElligott, Zoe A.; Holmes, Andrew; Winder, Danny G.

    2008-01-01

    Extinction, a form of learning that has the ability to reshape learned behavior based on new experiences, has been heavily studied utilizing fear learning paradigms. Mechanisms underlying extinction of positive-valence associations, such as drug self-administration and place preference, are poorly understood yet may have important relevance to…

  4. Selective and protracted effect of nifedipine on fear memory extinction correlates with induced stress response.

    PubMed

    Waltereit, Robert; Mannhardt, Sönke; Nescholta, Sabine; Maser-Gluth, Christiane; Bartsch, Dusan

    2008-05-01

    Memory extinction, defined as a decrease of a conditioned response as a function of a non-reinforced conditioned stimulus presentation, has high biological and clinical relevance. Extinction is not a passive reversing or erasing of the plasticity associated with acquisition, but a novel, active learning process. Nifedipine blocks L-type voltage gated calcium channels (LVGCC) and has been shown previously to selectively interfere with the extinction, but not the acquisition, of fear memory. We studied here the effect of retrograde and anterograde shifts of nifedipine application, with respect to an extinction training, on the extinction of fear conditioning. Subcutaneous injection of 30 mg/kg nifedipine, at least up to 4 h before the extinction session, significantly impaired extinction, as did intraperitoneal injection of 15 mg/kg nifedipine, at least up to 2 h before extinction training. However, the injection of nifedipine also induced a strong and protracted stress response. The pharmacokinetics of nifedipine suggest that it was mainly this stress response that triggered the specific inhibition of extinction, not the blockade of LVGCC in the brain. Our results support recent findings that stress selectively interferes with the extinction, but not the acquisition, of fear memory. They also indicate that a pharmacological approach is not sufficient to study the role of brain LVGCC in learning and memory. Further research using specific genetically modified animals is necessary to delineate the role of LVGCC in fear memory extinction.

  5. Selective and protracted effect of nifedipine on fear memory extinction correlates with induced stress response

    PubMed Central

    Waltereit, Robert; Mannhardt, Sönke; Nescholta, Sabine; Maser-Gluth, Christiane; Bartsch, Dusan

    2008-01-01

    Memory extinction, defined as a decrease of a conditioned response as a function of a non-reinforced conditioned stimulus presentation, has high biological and clinical relevance. Extinction is not a passive reversing or erasing of the plasticity associated with acquisition, but a novel, active learning process. Nifedipine blocks L-type voltage gated calcium channels (LVGCC) and has been shown previously to selectively interfere with the extinction, but not the acquisition, of fear memory. We studied here the effect of retrograde and anterograde shifts of nifedipine application, with respect to an extinction training, on the extinction of fear conditioning. Subcutaneous injection of 30 mg/kg nifedipine, at least up to 4 h before the extinction session, significantly impaired extinction, as did intraperitoneal injection of 15 mg/kg nifedipine, at least up to 2 h before extinction training. However, the injection of nifedipine also induced a strong and protracted stress response. The pharmacokinetics of nifedipine suggest that it was mainly this stress response that triggered the specific inhibition of extinction, not the blockade of LVGCC in the brain. Our results support recent findings that stress selectively interferes with the extinction, but not the acquisition, of fear memory. They also indicate that a pharmacological approach is not sufficient to study the role of brain LVGCC in learning and memory. Further research using specific genetically modified animals is necessary to delineate the role of LVGCC in fear memory extinction. PMID:18441293

  6. Time-dependent retrograde amnesic effects of muscimol on conditioned taste aversion extinction

    PubMed Central

    DiSorbo, Anthony; Wilson, Gina N.; Bacik, Stephanie; Hoxha, Zana; Biada, Jaclyn M.; Mickley, G. Andrew

    2009-01-01

    We explored how stimulation of GABAA receptors at different times during conditioned taste aversion (CTA) acquisition or extinction influenced extinction. In Experiment 1, rats acquired a CTA to 0.3% saccharin-flavored water (SAC) when it followed an injection of lithium chloride (LiCl; 81.0 mg/kg, i.p.). Following conditioning, rats received extinction training in which the GABAA agonist muscimol (1.0 mg/kg, i.p.), or control (saline) injections, were administered either before or after each extinction trial. Muscimol hindered extinction when administered after extinction trials. Muscimol’s inhibitory effects may have impeded extinction learning by disrupting synaptic mechanisms required to consolidate information experienced during extinction training. In Experiment 2, we studied the effects of muscimol on CTA acquisition and subsequent extinction. Rats received muscimol (1.0 mg/kg, i.p.) either before or after CTA conditioning trials. Following CTA acquisition, all rats were given CTA extinction training without muscimol administration. All groups developed CTA, but the group that received muscimol before CTA conditioning trials extinguished rapidly in comparison to other treatment groups. Differences between muscimol’s effects on CTA conditioning and CTA extinction indicate that fear conditioning and extinction involve, to some degree, different neuronal mechanisms. PMID:19171164

  7. Inhibition of Rac1 activity in the hippocampus impaired extinction of contextual fear.

    PubMed

    Jiang, Lizhu; Mao, Rongrong; Tong, Jianbin; Li, Jinnan; Chai, Anping; Zhou, Qixin; Yang, Yuexiong; Wang, Liping; Li, Lingjiang; Xu, Lin

    2016-10-01

    Promoting extinction of fear memory is the main treatment of fear disorders, especially post-traumatic stress disorder (PTSD). However, fear extinction is often incomplete in these patients. Our previous study had shown that Rac1 activity in hippocampus plays a crucial role in the learning of contextual fear memory in rats. Here, we further investigated whether Rac1 activity also modulated the extinction of contextual fear memory. We found that massed extinction obviously upregulated hippocampal Rac1 activity and induced long-term extinction of contextual fear in rats. Intrahippocampal injection of the Rac1 inhibitor NSC23766 prevents extinction of contextual fear in massed extinction training rats. In contrast, long-spaced extinction downregulated Rac1 activity and caused less extinction. And Rac1 activator CN04-A promotes extinction of contextual fear in long-spaced extinction rats. Our study demonstrates that inhibition of Rac1 activity in the hippocampus impaired extinction of contextual fear, suggesting that modulating Rac1 activity of the hippocampus may be promising therapy of fear disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. No impact of repeated extinction exposures on operant responding maintained by different reinforcer rates.

    PubMed

    Bai, John Y H; Podlesnik, Christopher A

    2017-05-01

    Greater rates of intermittent reinforcement in the presence of discriminative stimuli generally produce greater resistance to extinction, consistent with predictions of behavioral momentum theory. Other studies reveal more rapid extinction with higher rates of reinforcers - the partial reinforcement extinction effect. Further, repeated extinction often produces more rapid decreases in operant responding due to learning a discrimination between training and extinction contingencies. The present study examined extinction repeatedly with training with different rates of intermittent reinforcement in a multiple schedule. We assessed whether repeated extinction would reverse the pattern of greater resistance to extinction with greater reinforcer rates. Counter to this prediction, resistance to extinction was consistently greater across twelve assessments of training followed by six successive sessions of extinction. Moreover, patterns of responding during extinction resembled those observed during satiation tests, which should not alter discrimination processes with repeated testing. These findings join others suggesting operant responding in extinction can be durable across repeated tests. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Empirical support for an involvement of the mesostriatal dopamine system in human fear extinction.

    PubMed

    Raczka, K A; Mechias, M-L; Gartmann, N; Reif, A; Deckert, J; Pessiglione, M; Kalisch, R

    2011-06-07

    Exposure therapy for anxiety disorders relies on the principle of confronting a patient with the triggers of his fears, allowing him to make the unexpected safety experience that his fears are unfounded and resulting in the extinction of fear responses. In the laboratory, fear extinction is modeled by repeatedly presenting a fear-conditioned stimulus (CS) in the absence of the aversive unconditioned stimulus (UCS) to which it had previously been associated. Classical associative learning theory considers extinction to be driven by an aversive prediction error signal that expresses the expectation violation when not receiving an expected UCS and establishes a prediction of CS non-occurrence. Insufficiencies of this account in explaining various extinction-related phenomena could be resolved by assuming that extinction is an opponent appetitive-like learning process that would be mediated by the mesostriatal dopamine (DA) system. In accordance with this idea, we find that a functional polymorphism in the DA transporter gene, DAT1, which is predominantly expressed in the striatum, significantly affects extinction learning rates. Carriers of the 9-repeat (9R) allele, thought to confer enhanced phasic DA release, had higher learning rates. Further, functional magnetic resonance imaging revealed stronger hemodynamic appetitive prediction error signals in the ventral striatum in 9R carriers. Our results provide a first hint that extinction learning might indeed be conceptualized as an appetitive-like learning process and suggest DA as a new candidate neurotransmitter for human fear extinction. They open up perspectives for neurobiological therapy augmentation.

  10. Chronic Antidepressant Treatment Impairs the Acquisition of Fear Extinction

    PubMed Central

    Burghardt, Nesha S.; Sigurdsson, Torfi; Gorman, Jack M.; McEwen, Bruce S.; LeDoux, Joseph E.

    2012-01-01

    Background Like fear conditioning, the acquisition phase of extinction involves new learning that is mediated by the amygdala. During extinction training, the conditioned stimulus is repeatedly presented in the absence of the unconditioned stimulus and the expression of previously learned fear gradually becomes suppressed. Our previous study revealed that chronic treatment with a selective serotonin reuptake inhibitor (SSRI) impairs the acquisition of auditory fear conditioning. To gain further insight into how SSRIs affect fear learning, we tested the effects of chronic SSRI treatment on the acquisition of extinction. Methods Rats were treated chronically (22 days) or subchronically (9 days) with the SSRI citalopram (10 mg/kg/day) before extinction training. The results were compared to those following chronic and subchronic treatment with tianeptine (10 mg/kg/day), an antidepressant with a different method of action. The expression of the NR2B subunit of the NMDA receptor in the amygdala was examined after behavioral testing. Results Chronic but not subchronic administration of citalopram impaired the acquisition of extinction and downregulated the NR2B subunit of the NMDA receptor in the lateral and basal nuclei of the amygdala. Similar behavioral and molecular changes were found with tianeptine treatment. Conclusions These results provide further evidence that chronic antidepressant treatment can impair amygdala-dependent learning. Our findings are consistent with a role for glutamatergic neurotransmission in the final common pathway of antidepressant treatment. PMID:23260230

  11. MEST- avoid next extinction

    NASA Astrophysics Data System (ADS)

    Cao, Dayong

    2012-11-01

    Asteroid 2011 AG5 will impact on Earth in 2040. (See Donald K. Yoemans, ``Asteroid 2011 AG5 - A Reality Check,'' NASA-JPL, 2012) In 2011, The author say: the dark hole will take the dark comet to impact our solar system in 20 years, and give a systemic model between the sun and its companion-dark hole to explain why were there periodicity mass extinction on earth. (see Dayong Cao, BAPS.2011.CAL.C1.7, BAPS.2011.DFD.LA.24, BAPS.2012.APR.K1.78 and BAPS.2011.APR.K1.17) The dark Asteroid 2011 AG5 (as a dark comet) is made of the dark matter which has a space-time (as frequence-amplitude square) center- a different systemic model from solar systemic model. It can asborb the space-time and wave. So it is ``dark.'' When many dark matters hit on our earth, they can break our atom structure and our genetic code to trigger the Mass Extinction. In our experiments, consciousness can change the systematic model and code by a life-informational technology. So it can change the output signals of the solar cell. (see Dayong Cao, BAPS.2011.MAR.C1.286 and BAPS.2012.MAR.P33.14) So we will develop the genetic code of lives to evolution and sublimation, will use the dark matter to change the systemic model between dark hole and sun and will avoid next extinction.

  12. Extinction events can accelerate evolution.

    PubMed

    Lehman, Joel; Miikkulainen, Risto

    2015-01-01

    Extinction events impact the trajectory of biological evolution significantly. They are often viewed as upheavals to the evolutionary process. In contrast, this paper supports the hypothesis that although they are unpredictably destructive, extinction events may in the long term accelerate evolution by increasing evolvability. In particular, if extinction events extinguish indiscriminately many ways of life, indirectly they may select for the ability to expand rapidly through vacated niches. Lineages with such an ability are more likely to persist through multiple extinctions. Lending computational support for this hypothesis, this paper shows how increased evolvability will result from simulated extinction events in two computational models of evolved behavior. The conclusion is that although they are destructive in the short term, extinction events may make evolution more prolific in the long term.

  13. Extinction Events Can Accelerate Evolution

    PubMed Central

    Lehman, Joel; Miikkulainen, Risto

    2015-01-01

    Extinction events impact the trajectory of biological evolution significantly. They are often viewed as upheavals to the evolutionary process. In contrast, this paper supports the hypothesis that although they are unpredictably destructive, extinction events may in the long term accelerate evolution by increasing evolvability. In particular, if extinction events extinguish indiscriminately many ways of life, indirectly they may select for the ability to expand rapidly through vacated niches. Lineages with such an ability are more likely to persist through multiple extinctions. Lending computational support for this hypothesis, this paper shows how increased evolvability will result from simulated extinction events in two computational models of evolved behavior. The conclusion is that although they are destructive in the short term, extinction events may make evolution more prolific in the long term. PMID:26266804

  14. Taste-immunosuppression engram: reinforcement and extinction.

    PubMed

    Niemi, Maj-Britt; Härting, Margarete; Kou, Wei; Del Rey, Adriana; Besedovsky, Hugo O; Schedlowski, Manfred; Pacheco-López, Gustavo

    2007-08-01

    Several Pavlovian conditioning paradigms have documented the brain's abilities to sense immune-derived signals or immune status, associate them with concurrently relevant extereoceptive stimuli, and reinstate such immune responses on demand. Specifically, the naturalistic relation of food ingestion with its possible immune consequences facilitates taste-immune associations. Here we demonstrate that the saccharin taste can be associated with the immunosuppressive agent cyclosporine A, and that such taste-immune associative learning is subject to reinforcement. Furthermore, once consolidated, this saccharin-immunosuppression engram is resistant to extinction when avoidance behavior is assessed. More importantly, the more this engram is activated, either at association or extinction phases, the more pronounced is the conditioned immunosuppression.

  15. HDAC1 regulates fear extinction in mice.

    PubMed

    Bahari-Javan, Sanaz; Maddalena, Andrea; Kerimoglu, Cemil; Wittnam, Jessica; Held, Torsten; Bähr, Mathias; Burkhardt, Susanne; Delalle, Ivanna; Kügler, Sebastian; Fischer, Andre; Sananbenesi, Farahnaz

    2012-04-11

    Histone acetylation has been implicated with the pathogenesis of neuropsychiatric disorders and targeting histone deacetylases (HDACs) using HDAC inhibitors was shown to be neuroprotective and to initiate neuroregenerative processes. However, little is known about the role of individual HDAC proteins during the pathogenesis of brain diseases. HDAC1 was found to be upregulated in patients suffering from neuropsychiatric diseases. Here, we show that virus-mediated overexpression of neuronal HDAC1 in the adult mouse hippocampus specifically affects the extinction of contextual fear memories, while other cognitive abilities were unaffected. In subsequent experiments we show that under physiological conditions, hippocampal HDAC1 is required for extinction learning via a mechanism that involves H3K9 deacetylation and subsequent trimethylation of target genes. In conclusion, our data show that hippocampal HDAC1 has a specific role in memory function.

  16. Absence and leave; sick leave. Final rule.

    PubMed

    2010-12-03

    The U.S. Office of Personnel Management is issuing final regulations on the use of sick leave and advanced sick leave for serious communicable diseases, including pandemic influenza when appropriate. We are also permitting employees to substitute up to 26 weeks of accrued or accumulated sick leave for unpaid Family and Medical Leave Act (FMLA) leave to care for a seriously injured or ill covered servicemember, as authorized under the National Defense Authorization Act for Fiscal Year 2008, including up to 30 days of advanced sick leave for this purpose. Finally, we are reorganizing the existing sick leave regulations to enhance reader understanding and administration of the program.

  17. The Memory System Engaged During Acquisition Determines the Effectiveness of Different Extinction Protocols

    PubMed Central

    Goodman, Jarid; Packard, Mark G.

    2015-01-01

    Previous research indicates that extinction of rodent maze behavior may occur without explicit performance of the previously acquired response. In latent extinction, confining an animal to a previously rewarded goal location without reinforcement is typically sufficient to produce extinction of maze learning. However, previous studies have not determined whether latent extinction may be successfully employed to extinguish all types of memory acquired in the maze, or whether only specific types of memory may be vulnerable to latent extinction. The present study examined whether latent extinction may be effective across two plus-maze tasks that depend on anatomically distinct neural systems. Adult male Long-Evans rats were trained in a hippocampus-dependent place learning task (Experiment 1), in which animals were trained to approach a consistent spatial location for food reward. A separate group of rats were trained in a dorsolateral striatum-dependent response learning task (Experiment 2), in which animals were trained to make a consistent egocentric body-turn response for food reward. Following training, animals received response extinction or latent extinction. For response extinction, animals were given the opportunity to execute the original running approach response toward the empty food cup. For latent extinction, animals were confined to the original goal locations with the empty food cup, thus preventing them from making the original running approach response. Results indicate that, relative to no extinction, latent extinction was effective at extinguishing memory in the place learning task, but remained ineffective in the response learning task. In contrast, typical response extinction remained very effective at extinguishing memory in both place and response learning tasks. The present findings confirm that extinction of maze learning may occur with or without overt performance of the previously acquired response, but that the effectiveness of latent

  18. Belief bias and the extinction of induced fear.

    PubMed

    Vroling, Maartje S; de Jong, Peter J

    2013-01-01

    Some people show slower extinction of UCS expectancies than other people. Little is known about what predicts such delayed extinction. Extinction requires that people deduce the logical implication of corrective experiences challenging the previously learned CS-UCS contingency. "A strong habitual tendency to confirm beliefs" may therefore be a powerful mechanism immunising against refutation of UCS expectancies. This study investigated whether individual differences in such a belief confirming tendency (a process called "belief bias") may help in explaining individual differences in extinction. We tested whether relatively strong belief bias predicts delayed extinction of experimentally induced UCS expectancies. In a differential aversive conditioning paradigm, we used UCS-irrelevant (Experiment 1) and UCS-relevant (Experiment 2) pictorial stimuli as CS⁺ and CS⁻, and electrical stimulation as UCS. Belief bias indeed predicted delayed extinction of UCS expectancies when the CS⁺ was UCS-relevant (as is typically the case for phobic stimuli, Experiment 2). The study provides preliminary evidence that enhanced belief bias may indeed play a role in the persistence of UCS expectancies, and can thereby contribute to the development and persistence of anxiety disorders. The results also point to the relevance of reasoning tendencies in the search for predictors of delayed extinction of UCS expectancies.

  19. Attenuating fearful memories: effect of cued extinction on intrusions.

    PubMed

    Marks, Elizabeth H; Zoellner, Lori A

    2014-12-01

    Exposure-based therapies for posttraumatic stress disorder are thought to reduce intrusive memories through extinction processes. Methods that enhance extinction may translate to improved treatment. Rat research suggests retrieving a memory via a conditioned stimulus (CS) cue, and then modifying the retrieved memory within a specific reconsolidation window may enhance extinction. In humans, studies (e.g., Kindt & Soeter, 2013; Schiller et al., 2010) using basic learning paradigms show discrepant findings. Using a distressing film paradigm, participants (N = 148) completed fear acquisition and extinction. At extinction, they were randomized to 1 of 3 groups: CS cue within reconsolidation window, CS cue outside window, or non-CS cue within window. Intrusions were assessed 24 hr after extinction. Participants receiving the CS cue and completing extinction within the reconsolidation window had more intrusions (M = 2.40, SD = 2.54) than those cued outside (M = 1.65, SD = 1.70) or those receiving a non-CS cue (M = 1.24, SD = 1.26), F(2, 145) = 4.52, p = .01, d = 0.55. Consistent with the reconsolidation hypothesis, presenting a CS cue does appear to activate a specific period of time during which a memory can be updated. However, the CS cue caused increased, rather than decreased, frequency of intrusions. Understanding parameters of preextinction cueing may help us better understand reconsolidation as a potential memory updating mechanism.

  20. Middle mississippian blastoid extinction event.

    PubMed

    Ausich, W I; Meyer, D L; Waters, J A

    1988-05-06

    The Middle Mississippian blastoid (Phylum Echinodermata) extinction event (about 340 million years ago) was a rapid, habitat-specific extinction. Blastoids became rare or absent in shallow-water environments after the extinction, and this change was probably synchronous worldwide. Onshore-offshore habitat shifts have been recognized as an important historical trend among marine benthos. Unlike trends exhibited by other groups, blastoids appear to have repopulated shallow-water habitats after a period of diminished diversity and abundance.

  1. The Industrial Base: Facing Extinction

    DTIC Science & Technology

    1992-03-10

    INDUSTRIAL BASE.. FACING EXTINCTION ., TIc LECTE BY UN02 1992 - MR. DAVID L. THOMAS Department of the Army Civilian , 4...Industrial Base: Facing Extinction 12. PERSONAL AUTHOR(S) David L. Thomas, DAC, GM-15 13a. TYPE OF REPORT 13b. TIME COVERED 14. DATE OF REPORT (Year, Month...service or government agency. The Industrial Base: Accesioti For Facing Extinction NTIS CRA&IDTIC TAB D] Uanc,ounced 0 Justification AN INDIVIDUAL

  2. The impact of mass extinctions

    NASA Technical Reports Server (NTRS)

    Flessa, Karl W.

    1988-01-01

    In the years since Snowbird an explosive growth of research on the patterns, causes, and consequences of extinction was seen. The fossil record of extinction is better known, stratigraphic sections were scrutinized in great detail, and additional markers of environmental change were discovered in the rock record. However flawed, the fossil record is the only record that exists of natural extinction. Compilations from the primary literature contain a faint periodic signal: the extinctions of the past 250 my may be regulary spaced. The reality of the periodicity remains a subject for debate. The implications of periodicity are so profound that the debate is sure to continue. The greater precision from stratigraphic sections spanning extinction events has yet to resolve controversies concerning the rates at which extinctions occurred. Some sections seem to record sudden terminations, while others suggest gradual or steplike environmental deterioration. Unfortunately, the manner in which the strata record extinctions and compile stratigraphic ranges makes a strictly literal reading of the fossil record inadvisable. Much progress was made in the study of mass extinctions. The issues are more sharply defined but they are not fully resolved. Scenarios should look back to the phenomena they purport to explain - not just an iridium-rich layer, but the complex fabric of a mass extinction.

  3. Periodicity in marine extinction events

    NASA Technical Reports Server (NTRS)

    Sepkoski, J. John, Jr.; Raup, David M.

    1986-01-01

    The periodicity of extinction events is examined in detail. In particular, the temporal distribution of specific, identifiable extinction events is analyzed. The nature and limitations of the data base on the global fossil record is discussed in order to establish limits of resolution in statistical analyses. Peaks in extinction intensity which appear to differ significantly from background levels are considered, and new analyses of the temporal distribution of these peaks are presented. Finally, some possible causes of periodicity and of interdependence among extinction events over the last quarter billion years of earth history are examined.

  4. Periodicity in marine extinction events

    NASA Technical Reports Server (NTRS)

    Sepkoski, J. John, Jr.; Raup, David M.

    1986-01-01

    The periodicity of extinction events is examined in detail. In particular, the temporal distribution of specific, identifiable extinction events is analyzed. The nature and limitations of the data base on the global fossil record is discussed in order to establish limits of resolution in statistical analyses. Peaks in extinction intensity which appear to differ significantly from background levels are considered, and new analyses of the temporal distribution of these peaks are presented. Finally, some possible causes of periodicity and of interdependence among extinction events over the last quarter billion years of earth history are examined.

  5. Polyandry prevents extinction.

    PubMed

    Price, Tom A R; Hurst, Greg D D; Wedell, Nina

    2010-03-09

    Females of most animal species are polyandrous, with individual females usually mating with more than one male. However, the ubiquity of polyandry remains enigmatic because of the potentially high costs to females of multiple mating. Current theory to account for the high prevalence of polyandry largely focuses on its benefits to individual females. There are also higher-level explanations for the high incidence of polyandry-polyandrous clades may speciate more rapidly. Here we test the hypothesis that polyandry may also reduce population extinction risk. We demonstrate that mating with multiple males protects populations of the fruit fly Drosophila pseudoobscura against extinction caused by a "selfish" sex-ratio-distorting element. Thus, the frequency of female multiple mating in nature may be associated not only with individual benefits to females of this behavior but also with increased persistence over time of polyandrous species and populations. Furthermore, we show that female remating behavior can determine the frequency of sex-ratio distorters in populations. This may also be true for many other selfish genetic elements in natural populations.

  6. Avoid Earth Extinction

    NASA Astrophysics Data System (ADS)

    Cao, Dayong

    2012-11-01

    In 2011, the author supposes: the dark hole will take the dark comet to impact our solar system in 20 years. (see Dayong Cao, BAPS.2011.DFD.LA.24, BAPS.2012.APR.K1.78 and BAPS.2011.APR.K1.17) Asteroid 2011 AG5 will impact on Earth in 2040. (See Donald K. Yoemans, ``Asteroid 2011 AG5 - A Reality Check,'' NASA-JPL, 2012) The dark Asteroid 2011 AG5 (as a dark comet) is made of the dark matte. Sun and its companion-dark hole are a binary system (Their systemic model- SDS for short there in after). The dark hole has a dark comet belt. The dark hole and dark comet are made of the dark matter which has a space-time (as frequence-amplitude square) center- a different systemic model from solar systemic model. Because it absorb the space-time and wave. So it is ``dark.'' When the dark hole goes near the sun every 25-27 million years, it will take its dark comet belt to go into the solar system to impact our earth. In a other hand, it can change all of our systemic model and code which are controled by the SDS, such as the orbit both of the asteroid belt and planet (such as Jupiter), our atomic structure and our genetic code. It can trigger periodic Mass Extinction. We will use the dark matter to change the SDS to avoid forthcoming extinction.

  7. Sex differences and estrous cycle in female rats interact with the effects of fluoxetine treatment on fear extinction

    PubMed Central

    Lebrón-Milad, K.; Tsareva, A.; Ahmed, N.; Milad, M. R.

    2014-01-01

    A common treatment for anxiety disorders is chronic administration of selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine. Recent data suggest that SSRIs modulate fear responses after conditioned fear extinction and that gonadal hormones influence fear extinction. In this study we investigated the influence of sex and the estrous cycle on the effects of acute (experiment 1) and chronic (experiment 2) fluoxetine treatment on fear extinction. In experiment 1, rats received tone-footshock pairings during day 1. On day 2, rats received either fluoxetine (10mg/kg in 0.5mL) or vehicle prior to extinction learning. On day 3, extinction memory was assessed during extinction recall. In experiment 2, rats were exposed to a similar behavioral protocol, except that fluoxetine and vehicle were administered for 14 consecutives days after conditioning (days 2–15). Extinction learning and extinction recall occurred on days 15 and 16, respectively. Acute administration of fluoxetine increased fear responses equally in males and females during extinction learning and extinction recall. Chronic administration of fluoxetine reduced fear responses during extinction learning and extinction recall in female but not in male rats and this effect seems to be modulated by the estrous cycle. The SSRI-induced reduction of freezing during extinction learning and recall suggest a general anxiolytic effect of the drug treatment rather than a specific effect on extinction learning per se. Our data show evidence of sex-specific anxiolytic effects of 14-day treatment of fluoxetine while the acute anxiogenic effect of SSRI seems independent of sex effects. PMID:23886596

  8. Modulation of fear extinction processes using transcranial electrical stimulation

    PubMed Central

    Abend, R; Jalon, I; Gurevitch, G; Sar-el, R; Shechner, T; Pine, D S; Hendler, T; Bar-Haim, Y

    2016-01-01

    Research associates processes of fear conditioning and extinction with treatment of anxiety and stress-related disorders. Manipulation of these processes may therefore be beneficial for such treatment. The current study examines the effects of electrical brain stimulation on fear extinction processes in healthy humans in order to assess its potential relevance for treatment enhancement. Forty-five participants underwent a 3-day fear conditioning and extinction paradigm. Electrical stimulation targeting the medial prefrontal cortex was applied during the extinction-learning phase (Day 2). Participants were randomly assigned to three stimulation conditions: direct-current (DC) stimulation, aimed at enhancing extinction-learning; low-frequency alternating-current (AC) stimulation, aimed at interfering with reconsolidation of the activated fear memory; and sham stimulation. The effect of stimulation on these processes was assessed in the subsequent extinction recall phase (Day 3), using skin conductance response and self-reports. Results indicate that AC stimulation potentiated the expression of fear response, whereas DC stimulation led to overgeneralization of fear response to non-reinforced stimuli. The current study demonstrates the capability of electrical stimulation targeting the medial prefrontal cortex to modulate fear extinction processes. However, the stimulation parameters tested here yielded effects opposite to those anticipated and could be clinically detrimental. These results highlight the potential capacity of stimulation to manipulate processes relevant for treatment of anxiety and stress-related disorders, but also emphasize the need for additional research to identify delivery parameters to enable its translation into clinical practice. Clinical trial identifiers: Modulation of Fear Extinction Processes Using Transcranial Electrical Stimulation; https://clinicaltrials.gov/show/NCT02723188; NCT02723188 NCT02723188. PMID:27727241

  9. Extinction during reconsolidation of threat memory diminishes prefrontal cortex involvement

    PubMed Central

    Schiller, Daniela; Kanen, Jonathan W.; LeDoux, Joseph E.; Monfils, Marie-H.; Phelps, Elizabeth A.

    2013-01-01

    Controlling learned defensive responses through extinction does not alter the threat memory itself, but rather regulates its expression via inhibitory influence of the prefrontal cortex (PFC) over amygdala. Individual differences in amygdala–PFC circuitry function have been linked to trait anxiety and posttraumatic stress disorder. This finding suggests that exposure-based techniques may actually be least effective in those who suffer from anxiety disorders. A theoretical advantage of techniques influencing reconsolidation of threat memories is that the threat representation is altered, potentially diminishing reliance on this PFC circuitry, resulting in a more persistent reduction of defensive reactions. We hypothesized that timing extinction to coincide with threat memory reconsolidation would prevent the return of defensive reactions and diminish PFC involvement. Two conditioned stimuli (CS) were paired with shock and the third was not. A day later, one stimulus (reminded CS+) but not the other (nonreminded CS+) was presented 10 min before extinction to reactivate the threat memory, followed by extinction training for all CSs. The recovery of the threat memory was tested 24 h later. Extinction of the nonreminded CS+ (i.e., standard extinction) engaged the PFC, as previously shown, but extinction of the reminded CS+ (i.e., extinction during reconsolidation) did not. Moreover, only the nonreminded CS+ memory recovered on day 3. These results suggest that extinction during reconsolidation prevents the return of defensive reactions and diminishes PFC involvement. Reducing the necessity of the PFC–amygdala circuitry to control defensive reactions may help overcome a primary obstacle in the long-term efficacy of current treatments for anxiety disorders. PMID:24277809

  10. Extinction from a Rationalist Perspective

    PubMed Central

    Gallistel, C. R.

    2012-01-01

    The merging of the computational theory of mind and evolutionary thinking leads to a kind of rationalism, in which enduring truths about the world have become implicit in the computations that enable the brain to cope with the experienced world. The dead reckoning computation, for example, is implemented within the brains of animals as one of the mechanisms that enables them to learn where they are (Gallistel, 1990, 1995). It integrates a velocity signal with respect to a time signal. Thus, the manner in which position and velocity relate to one another in the world is reflected in the manner in which signals representing those variables are processed in the brain. I use principles of information theory and Bayesian inference to derive from other simple principles explanations for: 1) the failure of partial reinforcement to increase reinforcements to acquisition; 2) the partial reinforcement extinction effect; 3) spontaneous recovery; 4) renewal; 5) reinstatement; 6) resurgence (aka facilitated reacquisition). Like the principle underlying dead-reckoning, these principles are grounded in analytic considerations. They are the kind of enduring truths about the world that are likely to have shaped the brain's computations. PMID:22391153

  11. Extinction from a rationalist perspective.

    PubMed

    Gallistel, C R

    2012-05-01

    The merging of the computational theory of mind and evolutionary thinking leads to a kind of rationalism, in which enduring truths about the world have become implicit in the computations that enable the brain to cope with the experienced world. The dead reckoning computation, for example, is implemented within the brains of animals as one of the mechanisms that enables them to learn where they are (Gallistel, 1990, 1995). It integrates a velocity signal with respect to a time signal. Thus, the manner in which position and velocity relate to one another in the world is reflected in the manner in which signals representing those variables are processed in the brain. I use principles of information theory and Bayesian inference to derive from other simple principles explanations for: (1) the failure of partial reinforcement to increase reinforcements to acquisition; (2) the partial reinforcement extinction effect; (3) spontaneous recovery; (4) renewal; (5) reinstatement; (6) resurgence (aka facilitated reacquisition). Like the principle underlying dead-reckoning, these principles are grounded in analytic considerations. They are the kind of enduring truths about the world that are likely to have shaped the brain's computations.

  12. Leaving liza.

    PubMed

    Futcher, Jane

    2004-01-01

    Abstract This is Chapter Thirteen of Leaving Liza, a novel about life, death, love, friendship, jealousy and lesbian ex-lovers. In the novel, six women are spending the weekend at a beach house in Long Island's Hamptons, where they have gathered to be with their friend Liza, who is battling terminal ovarian cancer. Liza's lover, Jill, has agreed to the house party and helped plan the guest list. But, as she smolders with resentment at the attention Liza is getting and the depth of the women's friendships, she begins to come unraveled. After a severe asthma attack that requires an emergency room visit the day before, Jill conducts a seance, purporting to have contacted another of Liza's ex-lovers, who died a few months earlier. Now, on this last night of the house party, she lets Liza and her friends know what she's really feeling. The editors have asked me to add some "commentary" on the questions this story raises about the roles of ex-lovers. I would hope the scene reflects some of the tensions that can occur when ex-lovers choose to remain friends, particularly when those bonds provoke profound jealousy in both current and ex-lovers. For many of us, the job of assuaging and reassuring the current lover while maintaining intimate friendships with an ex-lover is simply too exhausting and prickly to endure. For others, it is worth the struggle. Liza and her friends clearly think it is. But at what point, they all wonder at this house party, does their hunger for honesty and their anger at being insulted and manipulated become more important than keeping the peace, and possibly their friendship with Liza? Perhaps only Liza's death will free them from this compromising coexistence.

  13. Extinction of Cocaine Seeking Requires a Window of Infralimbic Pyramidal Neuron Activity after Unreinforced Lever Presses.

    PubMed

    Gutman, Andrea L; Nett, Kelle E; Cosme, Caitlin V; Worth, Wensday R; Gupta, Subhash C; Wemmie, John A; LaLumiere, Ryan T

    2017-06-21

    The infralimbic cortex (IL) mediates extinction learning and the active suppression of cocaine-seeking behavior. However, the precise temporal relationship among IL activity, lever pressing, and extinction learning is unclear. To address this issue, we used activity-guided optogenetics in male Sprague Dawley rats to silence IL pyramidal neurons optically for 20 s immediately after unreinforced lever presses during early extinction training after cocaine self-administration. Optical inhibition of the IL increased active lever pressing during shortened extinction sessions, but did not alter the retention of the extinction learning as assessed in ensuing extinction sessions with no optical inhibition. During subsequent cued reinstatement sessions, rats that had previously received optical inhibition during the extinction sessions showed increased cocaine-seeking behavior. These findings appeared to be specific to inhibition during the post-lever press period because IL inhibition given in a noncontingent, pseudorandom manner during extinction sessions did not produce the same effects. Illumination alone (i.e., with no opsin expression) and food-seeking control experiments also failed to produce the same effects. In another experiment, IL inhibition after lever presses during cued reinstatement sessions increased cocaine seeking during those sessions. Finally, inhibition of the prelimbic cortex immediately after unreinforced lever presses during shortened extinction sessions decreased lever pressing during these sessions, but had no effect on subsequent reinstatement. These results indicate that IL activity immediately after unreinforced lever presses is necessary for normal extinction of cocaine seeking, suggesting that critical encoding of the new contingencies between a lever press and a cocaine reward occurs during that period.SIGNIFICANCE STATEMENT The infralimbic cortex (IL) contributes to the extinction of cocaine-seeking behavior, but the precise relationship

  14. The effects of compound stimulus extinction and inhibition of noradrenaline reuptake on the renewal of alcohol seeking

    PubMed Central

    Furlong, T M; Pan, M J; Corbit, L H

    2015-01-01

    Alcohol-related stimuli can trigger relapse of alcohol-seeking behaviors even after extended periods of abstinence. Extinction of such stimuli can reduce their impact on relapse; however, the expression of extinction can be disrupted when testing occurs outside the context where extinction learning took place, an effect termed renewal. Behavioral and pharmacological methods have recently been shown to augment extinction learning; yet, it is not known whether the improved expression of extinction following these treatments remains context-dependent. Here we examined whether two methods, compound–stimulus extinction and treatment with the noradrenaline reuptake inhibitor atomoxetine, would reduce the vulnerability of extinction to a change in context. Following alcohol self-administration, responding was extinguished in a distinct context. After initial extinction, further extinction was given to a target stimulus presented in compound with another alcohol-predictive stimulus intended to augment prediction error (Experiment 1) or after a systemic injection of atomoxetine (1.0 mg kg−1; Experiment 2). A stimulus extinguished as part of a compound elicited less responding than a stimulus receiving equal extinction alone regardless of whether animals were tested in the training or extinction context; however, reliable renewal was not observed in this paradigm. Importantly, atomoxetine enhanced extinction relative to controls even in the presence of a reliable renewal effect. Thus, extinction of alcohol-seeking behavior can be improved by extinguishing multiple alcohol-predictive stimuli or enhancing noradrenaline neurotransmission during extinction training. Importantly, both methods improve extinction even when the context is changed between extinction training and test, and thus could be utilized to enhance the outcome of extinction-based treatments for alcohol-use disorders. PMID:26327688

  15. The effects of compound stimulus extinction and inhibition of noradrenaline reuptake on the renewal of alcohol seeking.

    PubMed

    Furlong, T M; Pan, M J; Corbit, L H

    2015-09-01

    Alcohol-related stimuli can trigger relapse of alcohol-seeking behaviors even after extended periods of abstinence. Extinction of such stimuli can reduce their impact on relapse; however, the expression of extinction can be disrupted when testing occurs outside the context where extinction learning took place, an effect termed renewal. Behavioral and pharmacological methods have recently been shown to augment extinction learning; yet, it is not known whether the improved expression of extinction following these treatments remains context-dependent. Here we examined whether two methods, compound-stimulus extinction and treatment with the noradrenaline reuptake inhibitor atomoxetine, would reduce the vulnerability of extinction to a change in context. Following alcohol self-administration, responding was extinguished in a distinct context. After initial extinction, further extinction was given to a target stimulus presented in compound with another alcohol-predictive stimulus intended to augment prediction error (Experiment 1) or after a systemic injection of atomoxetine (1.0 mg kg(-1); Experiment 2). A stimulus extinguished as part of a compound elicited less responding than a stimulus receiving equal extinction alone regardless of whether animals were tested in the training or extinction context; however, reliable renewal was not observed in this paradigm. Importantly, atomoxetine enhanced extinction relative to controls even in the presence of a reliable renewal effect. Thus, extinction of alcohol-seeking behavior can be improved by extinguishing multiple alcohol-predictive stimuli or enhancing noradrenaline neurotransmission during extinction training. Importantly, both methods improve extinction even when the context is changed between extinction training and test, and thus could be utilized to enhance the outcome of extinction-based treatments for alcohol-use disorders.

  16. Fear extinction can be made state-dependent on peripheral epinephrine: role of norepinephrine in the nucleus tractus solitarius.

    PubMed

    Rosa, Jessica; Myskiw, Jociane C; Furini, Cristiane R G; Sapiras, Gerson G; Izquierdo, Ivan

    2014-09-01

    We investigate whether the extinction of inhibitory avoidance (IA) learning can be subjected to endogenous state-dependence with systemic injections of epinephrine (E), and whether endogenous norepinephrine (NE) and the nucleus tractus solitarius (NTS)→locus coeruleus→hippocampus/amygdala (HIPP/BLA) pathway participate in this. Rats trained in IA were submitted to two sessions of extinction 24 h apart: In the first, the animals were submitted to a training session of extinction, and in the second they were tested for the retention of extinction. Saline or E were given i.p. immediately after the extinction training (post-extinction training injections) and/or 6 min before the extinction test (pre-extinction test). Post-extinction training E (50 or 100 μg/kg) induced a poor retrieval of extinction in the test session of this task unless an additional E injection (50 μg/kg) was given prior to the extinction test. This suggested state-dependence. Muscimol (0.01 μg/side) microinfused into the NTS prior to the extinction test session blocked E-induced state-dependence. Norepinephrine (NE, 1 μg/side) infused bilaterally into NTS restores the extinction impairment caused by post-extinction training i.p. E. In animals with bilateral NTS blockade induced by muscimol, NE (1 μg/side) given prior to the extinction test into the CA1 region of the dorsal hippocampus or into the basolateral amygdala restored the normal extinction levels that had been impaired by muscimol. These results suggest a role for the NTS→locus coeruleus→HIPP/BLA pathway in the retrieval of extinction, as it has been shown to have in the consolidation of inhibitory avoidance and of object recognition learning.

  17. Extinction in multiple virtual reality contexts diminishes fear reinstatement in humans.

    PubMed

    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.

  18. D-cycloserine enhances generalization of fear extinction in children.

    PubMed

    Byrne, Simon P; Rapee, Ronald M; Richardson, Rick; Malhi, Gin S; Jones, Michael; Hudson, Jennifer L

    2015-06-01

    For exposure therapy to be successful, it is essential that fear extinction learning extends beyond the treatment setting. D-cycloserine (DCS) may facilitate treatment gains by increasing generalization of extinction learning, however, its effects have not been tested in children. We examined whether DCS enhanced generalization of fear extinction learning across different stimuli and contexts among children with specific phobias. The study was a double-blind placebo-controlled randomized controlled trial among dog or spider phobic children aged 6-14. Participants ingested either 50 mg of DCS (n = 18) or placebo (n = 17) before receiving a single prolonged exposure session to their feared stimulus. Return of fear was examined 1 week later to a different stimulus (a different dog or spider), presented in both the original treatment context and an alternate context. Avoidance and fear were measured with Behavior Approach Tests (BATs), where the child was asked to increase proximity to the stimulus while reporting their fear level. There were no differences in BAT performance between groups during the exposure session or when a new stimulus was later presented in the treatment context. However, when the new stimulus was presented in a different context, relative to placebo, the DCS group showed less avoidance (P = .03) and less increase in fear (P = .04) with moderate effect sizes. DCS enabled children to better retain their fear extinction learning. This new learning generalized to different stimuli and contexts. © 2015 Wiley Periodicals, Inc.

  19. Acoustic integrated extinction

    PubMed Central

    Norris, Andrew N.

    2015-01-01

    The integrated extinction (IE) is defined as the integral of the scattering cross section as a function of wavelength. Sohl et al. (2007 J. Acoust. Soc. Am. 122, 3206–3210. (doi:10.1121/1.2801546)) derived an IE expression for acoustic scattering that is causal, i.e. the scattered wavefront in the forward direction arrives later than the incident plane wave in the background medium. The IE formula was based on electromagnetic results, for which scattering is causal by default. Here, we derive a formula for the acoustic IE that is valid for causal and non-causal scattering. The general result is expressed as an integral of the time-dependent forward scattering function. The IE reduces to a finite integral for scatterers with zero long-wavelength monopole and dipole amplitudes. Implications for acoustic cloaking are discussed and a new metric is proposed for broadband acoustic transparency. PMID:27547100

  20. Originations and Extinctions

    NASA Astrophysics Data System (ADS)

    Ray, Tane; Moseley, Leo; Jan, Naeem

    We analyse the fossil data of Benton1 with and without interpolation schemes. By Fourier transform analysis, we find a frequency dependence of the amplitude of 1/f for the various interpolation schemes used in the past. We illustrate that shuffling the interpolated data changes the spectra only slightly. On the other hand, an identical analysis performed on the raw (uninterpolated) fossil data gives a flat frequency spectrum. We conclude that the 1/f behavior is an artifact of the interpolation schemes. We next introduce a simulation of extinctions driven only by interactions between two trophic levels. Fourier transform analysis of the simulation data shows a frequency dependence of 1/f. When the data are grouped into a form resembling the fossil record the frequency dependence vanishes, giving a flat spectrum. Our simulation produces a frequency spectrum that agrees with the observed fossil record.

  1. Timing, tempo and paleoenvironmental implications of Deccan volcanism relative to the KTB extinction, what we can learn from the red bole record?

    NASA Astrophysics Data System (ADS)

    Adatte, Thierry; Sordet, Valentin; Keller, Gerta; Schoene, Blair; Samperton, Kyle; Khadri, Syed

    2016-04-01

    Deccan Traps erupted in three main phases with 6% total Deccan volume in phase-1 (C30n), 80% in phase-2 (C29r) and 14% in phase-3 (C29n). Recent studies indicate that the bulk (80%) of Deccan trap eruptions (phase-2) occurred over a relatively short time interval in magnetic polarity C29r. U-Pb zircon geochronology shows that the main phase-2 began 250 ky before the Cretaceous-Tertiary (KT) mass extinction and continued into the early Danian suggesting a cause-and-effect relationship. In India a strong floral response is observed as a direct consequence of volcanic phase-2. Shortly after the onset of Deccan phase-2, the floral association dominated by gymnosperms and angiosperms was decimated as indicated by a sharp decrease in pollen and spores coupled with the appearance of fungi, which mark increasing stress conditions as a direct result of volcanic activity. The inter-trappean sediments deposited in phase-2 are characterized by the highest alteration CIA index values suggesting increased acid rains due to SO2 emissions. In addition, a sharp decrease in pollen and spores coupled with the appearance of fungi mark increasing stress conditions, which are likely a direct result of volcanic activity. Bulk organic geochemistry points to a strong degradation of the indigenous organic matter, suggesting that the biomass was oxidized in acidic conditions triggered by intense volcanic activity. Closer to the eruption center, the lava flows are generally separated by red weathered horizons known as red boles that mark quiescent periods between basalt flows. Red boles have increasingly attracted the attention of researchers to understand the climatic and paleoenvironmental impact of Continental Flood Basalts (CFB). Recent advances in U-Pb dating of Deccan lava flows, studies of weathering patterns and paleoclimatic information gained from multiproxy analyses of red bole beds (e.g., lithology, mineralogy, geochemistry) yield crucial evidence of environmental changes

  2. Measuring Extinction with ALE

    NASA Astrophysics Data System (ADS)

    Zimmer, Peter C.; McGraw, J. T.; Gimmestad, G. G.; Roberts, D.; Stewart, J.; Smith, J.; Fitch, J.

    2007-12-01

    ALE (Astronomical LIDAR for Extinction) is deployed at the University of New Mexico's (UNM) Campus Observatory in Albuquerque, NM. It has begun a year-long testing phase prior deployment at McDonald Observatory in support of the CCD/Transit Instrument II (CTI-II). ALE is designed to produce a high-precision measurement of atmospheric absorption and scattering above the observatory site every ten minutes of every moderately clear night. LIDAR (LIght Detection And Ranging) is the VIS/UV/IR analog of radar, using a laser, telescope and time-gated photodetector instead of a radio transmitter, dish and receiver. In the case of ALE -- an elastic backscatter LIDAR -- 20ns-long, eye-safe laser pulses are launched 2500 times per second from a 0.32m transmitting telescope co-mounted with a 50mm short-range receiver on an alt-az mounted 0.67m long-range receiver. Photons from the laser pulse are scattered and absorbed as the pulse propagates through the atmosphere, a portion of which are scattered into the field of view of the short- and long-range receiver telescopes and detected by a photomultiplier. The properties of a given volume of atmosphere along the LIDAR path are inferred from both the altitude-resolved backscatter signal as well as the attenuation of backscatter signal from altitudes above it. We present ALE profiles from the commissioning phase and demonstrate some of the astronomically interesting atmospheric information that can be gleaned from these data, including, but not limited to, total line-of-sight extinction. This project is funded by NSF Grant 0421087.

  3. Extinction of Harrington's Mountain Goat

    NASA Astrophysics Data System (ADS)

    Mead, Jim I.; Martin, Paul S.; Euler, Robert C.; Long, Austin; Jull, A. J. T.; Toolin, Laurence J.; Donahue, Douglas J.; Linick, T. W.

    1986-02-01

    Keratinous horn sheaths of the extinct Harrington's mountain goat, Oreamnos harringtoni, were recovered at or near the surface of dry caves of the Grand Canyon, Arizona. Twenty-three separate specimens from two caves were dated nondestructively by the tandem accelerator mass spectrometer (TAMS). Both the TAMS and the conventional dates indicate that Harrington's mountain goat occupied the Grand Canyon for at least 19,000 years prior to becoming extinct by 11,160 ± 125 radiocarbon years before present. The youngest average radiocarbon dates on Shasta ground sloths, Nothrotheriops shastensis, from the region are not significantly younger than those on extinct mountain goats. Rather than sequential extinction with Harrington's mountain goat disappearing from the Grand Canyon before the ground sloths, as one might predict in view of evidence of climatic warming at the time, the losses were concurrent. Both extinctions coincide with the regional arrival of Clovis hunters.

  4. Extinction of Harrington's mountain goat

    SciTech Connect

    Mead, J.I.; Martin, P.S.; Euler, R.C.; Long, A.; Jull, A.J.T.; Toolin, L.J.; Donahue, D.J.; Linick, T.W.

    1986-02-01

    Keratinous horn sheaths of the extinct Harrington's mountain goat, Oreamnos harringtoni, were recovered at or near the surface of dry caves of the Grand Canyon, Arizona. Twenty-three separate specimens from two caves were dated nondestructively by the tandem accelerator mass spectrometer (TAMS). Both the TAMS and the conventional dates indicate that Harrington's mountain goat occupied the Grand Canyon for at least 19,000 years prior to becoming extinct by 11,160 +/- 125 radiocarbon years before present. The youngest average radiocarbon dates on Shasta ground sloths, Nothrotheriops shastensis, from the region are not significantly younger than those on extinct mountain goats. Rather than sequential extinction with Harrington's mountain goat disappearing from the Grand Canyon before the ground sloths, as one might predict in view of evidence of climatic warming at the time, the losses were concurrent. Both extinctions coincide with the regional arrival of Clovis hunters.

  5. Extinction of Harrington's mountain goat

    PubMed Central

    Mead, Jim I.; Martin, Paul S.; Euler, Robert C.; Long, Austin; Jull, A. J. T.; Toolin, Laurence J.; Donahue, Douglas J.; Linick, T. W.

    1986-01-01

    Keratinous horn sheaths of the extinct Harrington's mountain goat, Oreamnos harringtoni, were recovered at or near the surface of dry caves of the Grand Canyon, Arizona. Twenty-three separate specimens from two caves were dated nondestructively by the tandem accelerator mass spectrometer (TAMS). Both the TAMS and the conventional dates indicate that Harrington's mountain goat occupied the Grand Canyon for at least 19,000 years prior to becoming extinct by 11,160 ± 125 radiocarbon years before present. The youngest average radiocarbon dates on Shasta ground sloths, Nothrotheriops shastensis, from the region are not significantly younger than those on extinct mountain goats. Rather than sequential extinction with Harrington's mountain goat disappearing from the Grand Canyon before the ground sloths, as one might predict in view of evidence of climatic warming at the time, the losses were concurrent. Both extinctions coincide with the regional arrival of Clovis hunters. Images PMID:16593655

  6. Interstellar extinction in the ultraviolet

    NASA Technical Reports Server (NTRS)

    Bless, R. C.; Savage, B. D.

    1972-01-01

    Interstellar extinction curves over the region 3600-1100 A for 17 stars are presented. The observations were made by the two Wisconsin spectrometers onboard the OAO-2 with spectral resolutions of 10 A and 20 A. The extinction curves generally show a pronounced maximum at 2175 plus or minus 25 A, a broad minimum in the region 1800-1350 A, and finally a rapid rise to the far ultraviolet. Large extinction variations from star to star are found, especially in the far ultraviolet; however, with only two possible exceptions in this sample, the wavelength at the maximum of the extinction bump is essentially constant. These data are combined with visual and infrared observations to display the extinction behavior over a range in wavelength of about a factor of 20.

  7. Pinpointing and preventing imminent extinctions

    PubMed Central

    Ricketts, Taylor H.; Dinerstein, Eric; Boucher, Tim; Brooks, Thomas M.; Butchart, Stuart H. M.; Hoffmann, Michael; Lamoreux, John F.; Morrison, John; Parr, Mike; Pilgrim, John D.; Rodrigues, Ana S. L.; Sechrest, Wes; Wallace, George E.; Berlin, Ken; Bielby, Jon; Burgess, Neil D.; Church, Don R.; Cox, Neil; Knox, David; Loucks, Colby; Luck, Gary W.; Master, Lawrence L.; Moore, Robin; Naidoo, Robin; Ridgely, Robert; Schatz, George E.; Shire, Gavin; Strand, Holly; Wettengel, Wes; Wikramanayake, Eric

    2005-01-01

    Slowing rates of global biodiversity loss requires preventing species extinctions. Here we pinpoint centers of imminent extinction, where highly threatened species are confined to single sites. Within five globally assessed taxa (i.e., mammals, birds, selected reptiles, amphibians, and conifers), we find 794 such species, three times the number recorded as having gone extinct since 1500. These species occur in 595 sites, concentrated in tropical forests, on islands, and in mountainous areas. Their taxonomic and geographical distribution differs significantly from that of historical extinctions, indicating an expansion of the current extinction episode beyond sensitive species and places toward the planet's most biodiverse mainland regions. Only one-third of the sites are legally protected, and most are surrounded by intense human development. These sites represent clear opportunities for urgent conservation action to prevent species loss. PMID:16344485

  8. Pinpointing and preventing imminent extinctions.

    PubMed

    Ricketts, Taylor H; Dinerstein, Eric; Boucher, Tim; Brooks, Thomas M; Butchart, Stuart H M; Hoffmann, Michael; Lamoreux, John F; Morrison, John; Parr, Mike; Pilgrim, John D; Rodrigues, Ana S L; Sechrest, Wes; Wallace, George E; Berlin, Ken; Bielby, Jon; Burgess, Neil D; Church, Don R; Cox, Neil; Knox, David; Loucks, Colby; Luck, Gary W; Master, Lawrence L; Moore, Robin; Naidoo, Robin; Ridgely, Robert; Schatz, George E; Shire, Gavin; Strand, Holly; Wettengel, Wes; Wikramanayake, Eric

    2005-12-20

    Slowing rates of global biodiversity loss requires preventing species extinctions. Here we pinpoint centers of imminent extinction, where highly threatened species are confined to single sites. Within five globally assessed taxa (i.e., mammals, birds, selected reptiles, amphibians, and conifers), we find 794 such species, three times the number recorded as having gone extinct since 1500. These species occur in 595 sites, concentrated in tropical forests, on islands, and in mountainous areas. Their taxonomic and geographical distribution differs significantly from that of historical extinctions, indicating an expansion of the current extinction episode beyond sensitive species and places toward the planet's most biodiverse mainland regions. Only one-third of the sites are legally protected, and most are surrounded by intense human development. These sites represent clear opportunities for urgent conservation action to prevent species loss.

  9. The end-Permian mass extinction: A complex, multicausal extinction

    NASA Technical Reports Server (NTRS)

    Erwin, D. H.

    1994-01-01

    The end-Permian mass extinction was the most extensive in the history of life and remains one of the most complex. Understanding its causes is particularly important because it anchors the putative 26-m.y. pattern of periodic extinction. However, there is no good evidence for an impact and this extinction appears to be more complex than others, involving at least three phases. The first began with the onset of a marine regression during the Late Permian and resulting elimination of most marine basins, reduction in habitat area, and increased climatic instability; the first pulse of tetrapod extinctions occurred in South Africa at this time. The second phase involved increased regression in many areas (although apparently not in South China) and heightened climatic instability and environmental degradation. Release of gas hydrates, oxidation of marine carbon, and the eruption of the Siberian flood basalts occurred during this phase. The final phase of the extinction episode began with the earliest Triassic marine regression and destruction of nearshore continental habitats. Some evidence suggests oceanic anoxia may have developed during the final phase of the extinction, although it appears to have been insufficient to the sole cause of the extinction.

  10. Extinction of conditioned inhibition through nonreinforced presentation of the inhibitor.

    PubMed

    Melchers, Klaus G; Wolff, Susann; Lachnit, Harald

    2006-08-01

    In previous studies that have tried to extinguish conditioned inhibition through nonreinforced presentations of the inhibitor, researchers have repeatedly failed to find evidence for such extinction. The present study revealed that extinction can be achieved through nonreinforcement of the inhibitor, depending on properties of the reinforcer. In a human causal learning experiment, we found complete extinction in a scenario in which the reinforcer could take on negative values. Thereby, this scenario reflected the assumed symmetrical continuum on which associative strength can vary, according to the Rescorla-Wagner theory of associative learning. In contrast to this, the inhibitory cue retained its inhibitory potential in another condition, in which the scenario did not allow negative values of the reinforcer.

  11. Extinction, Reacquisition, and Rapid Forgetting of Eyeblink Conditioning in Developing Rats

    ERIC Educational Resources Information Center

    Brown, Kevin L.; Freeman, John H.

    2014-01-01

    Eyeblink conditioning is a well-established model for studying the developmental neurobiology of associative learning and memory. However, age differences in extinction and subsequent reacquisition have yet to be studied using this model. The present study examined extinction and reacquisition of eyeblink conditioning in developing rats. In…

  12. Cannabinoid modulation of fear extinction brain circuits: a novel target to advance anxiety treatment.

    PubMed

    Rabinak, Christine A; Phan, K Luan

    2014-01-01

    Anxiety disorders, such as post-traumatic stress (PTSD), panic, and phobic disorders, can be conceptualized as a failure to inhibit inappropriate fear responses. A common, effective treatment strategy involves repeated presentations to the feared cue without any danger (extinction). However, extinction learning has a number of important limitations, and enhancing its effects, generalizability and durability via cognitive enhancers may improve its therapeutic impact. In this review we focus specifically on the role of the cannabinoid system in fear extinction learning and its retention. We address the following questions: What are the neural circuits mediating fear extinction?; Can we make fear extinction more effective?; Can cannabinoids facilitate fear extinction in humans?; How might the cannabinoid system effect fear extinction? Collectively, translational evidence suggest that enhancing cannabinoid transmission may facilitate extinction learning and its recall, and that the cannabinoid system is a potential pharmacological target for improving the active learning that occurs during exposure-based behavioral treatments prompting future research in terms of mechanisms research, novel treatment approaches ('cognitive enhancers'), and pharmacotherapeutic drug discovery.

  13. Evidence for Recovery of Fear Following Immediate Extinction in Rats and Humans

    ERIC Educational Resources Information Center

    Schiller, Daniela; Cain, Christopher K.; Curley, Nina G.; Schwartz, Jennifer S.; Stern, Sarah A.; LeDoux, Joseph E.; Phelps, Elizabeth A.

    2008-01-01

    Fear responses can be eliminated through extinction, a procedure involving the presentation of fear-eliciting stimuli without aversive outcomes. Extinction is believed to be mediated by new inhibitory learning that acts to suppress fear expression without erasing the original memory trace. This hypothesis is supported mainly by behavioral data…

  14. Evidence for Recovery of Fear Following Immediate Extinction in Rats and Humans

    ERIC Educational Resources Information Center

    Schiller, Daniela; Cain, Christopher K.; Curley, Nina G.; Schwartz, Jennifer S.; Stern, Sarah A.; LeDoux, Joseph E.; Phelps, Elizabeth A.

    2008-01-01

    Fear responses can be eliminated through extinction, a procedure involving the presentation of fear-eliciting stimuli without aversive outcomes. Extinction is believed to be mediated by new inhibitory learning that acts to suppress fear expression without erasing the original memory trace. This hypothesis is supported mainly by behavioral data…

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

    ERIC Educational Resources Information Center

    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…

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

    ERIC Educational Resources Information Center

    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…

  17. Sleep supports cued fear extinction memory consolidation independent of circadian phase.

    PubMed

    Melo, Irene; Ehrlich, Ingrid

    2016-07-01

    Sleep promotes memory, particularly for declarative learning. However, its role in non-declarative, emotional memories is less well understood. Some studies suggest that sleep may influence fear-related memories, and thus may be an important factor determining the outcome of treatments for emotional disorders such as post-traumatic stress disorder. Here, we investigated the effect of sleep deprivation and time of day on fear extinction memory consolidation. Mice were subjected to a cued Pavlovian fear and extinction paradigm at the beginning of their resting or active phase. Immediate post-extinction learning sleep deprivation for 5h compromised extinction memory when tested 24h after learning. Context-dependent extinction memory recall was completely prevented by sleep-manipulation during the resting phase, while impairment was milder during the active phase and extinction memory retained its context-specificity. Importantly, control experiments excluded confounding factors such as differences in baseline locomotion, fear generalization and stress hormone levels. Together, our findings indicate that post-learning sleep supports cued fear extinction memory consolidation in both circadian phases. The lack of correlation between memory efficacy and sleep time suggests that extinction memory may be influenced by specific sleep events in the early consolidation period.

  18. Selective and Protracted Effect of Nifedipine on Fear Memory Extinction Correlates with Induced Stress Response

    ERIC Educational Resources Information Center

    Waltereit, Robert; Mannhardt, Sonke; Nescholta, Sabine; Maser-Gluth, Christiane; Bartsch, Dusan

    2008-01-01

    Memory extinction, defined as a decrease of a conditioned response as a function of a non-reinforced conditioned stimulus presentation, has high biological and clinical relevance. Extinction is not a passive reversing or erasing of the plasticity associated with acquisition, but a novel, active learning process. Nifedipine blocks L-type voltage…

  19. Reexposure to the Amnestic Agent Alleviates Cycloheximide-Induced Retrograde Amnesia for Reactivated and Extinction Memories

    ERIC Educational Resources Information Center

    Briggs, James F.; Olson, Brian P.

    2013-01-01

    We investigated whether reexposure to an amnestic agent would reverse amnesia for extinction of learned fear similar to that of a reactivated memory. When cycloheximide (CHX) was administered immediately after a brief cue-induced memory reactivation (15 sec) and an extended extinction session (12 min) rats showed retrograde amnesia for both…

  20. The Role of the Medial Prefrontal Cortex in Trace Fear Extinction

    ERIC Educational Resources Information Center

    Kwapis, Janine L.; Jarome, Timothy J.; Helmstetter, Fred J.

    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…

  1. The Role of the Medial Prefrontal Cortex in Trace Fear Extinction

    ERIC Educational Resources Information Center

    Kwapis, Janine L.; Jarome, Timothy J.; Helmstetter, Fred J.

    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…

  2. Extinction, Reacquisition, and Rapid Forgetting of Eyeblink Conditioning in Developing Rats

    ERIC Educational Resources Information Center

    Brown, Kevin L.; Freeman, John H.

    2014-01-01

    Eyeblink conditioning is a well-established model for studying the developmental neurobiology of associative learning and memory. However, age differences in extinction and subsequent reacquisition have yet to be studied using this model. The present study examined extinction and reacquisition of eyeblink conditioning in developing rats. In…

  3. Selective and Protracted Effect of Nifedipine on Fear Memory Extinction Correlates with Induced Stress Response

    ERIC Educational Resources Information Center

    Waltereit, Robert; Mannhardt, Sonke; Nescholta, Sabine; Maser-Gluth, Christiane; Bartsch, Dusan

    2008-01-01

    Memory extinction, defined as a decrease of a conditioned response as a function of a non-reinforced conditioned stimulus presentation, has high biological and clinical relevance. Extinction is not a passive reversing or erasing of the plasticity associated with acquisition, but a novel, active learning process. Nifedipine blocks L-type voltage…

  4. Reexposure to the Amnestic Agent Alleviates Cycloheximide-Induced Retrograde Amnesia for Reactivated and Extinction Memories

    ERIC Educational Resources Information Center

    Briggs, James F.; Olson, Brian P.

    2013-01-01

    We investigated whether reexposure to an amnestic agent would reverse amnesia for extinction of learned fear similar to that of a reactivated memory. When cycloheximide (CHX) was administered immediately after a brief cue-induced memory reactivation (15 sec) and an extended extinction session (12 min) rats showed retrograde amnesia for both…

  5. D-cycloserine does not facilitate fear extinction by reducing conditioned stimulus processing or promoting conditioned inhibition to contextual cues.

    PubMed

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

    2012-09-14

    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 in conditioned stimulus (CS) processing or (2) by promoting the development of conditioned inhibition to contextual cues. Rats administered DCS prior to extinction showed enhanced long-term extinction retention (Experiments 3 and 4). The same nonreinforced CS procedure used in extinction also reduced freezing at test when presented as pre-exposure before conditioning, demonstrating latent inhibition (Experiment 1). DCS administered shortly prior to pre-exposure had no effect on latent inhibition using parameters which produced weak (Experiment 2) or strong (Experiment 3) expression of latent inhibition. Therefore, DCS facilitated learning involving CS-alone exposures, but only when these exposures occurred after (extinction) and not before (latent inhibition) conditioning. We also used a retardation test procedure to examine whether the extinction context gained inhibitory properties for rats given DCS prior to extinction. With three different footshock intensities, there was no evidence that DCS promoted accrual of associative inhibition to the extinction context (Experiment 4). The present findings demonstrate that DCS does not facilitate extinction by reducing CS processing or causing the extinction context to become a conditioned inhibitor. Investigations into the mechanisms underlying the augmentation of extinction by DCS are valuable for understanding how fear can be inhibited.

  6. Comparing Context Specificity of Extinction and Latent Inhibition

    PubMed Central

    Miller, Ralph R.; Laborda, Mario A.; Polack, Cody W.; Miguez, Gonzalo

    2015-01-01

    Exposure to a cue alone either before (i.e., latent inhibition treatment) or after (i.e., extinction) the cue is paired with an unconditioned stimulus (US) results in attenuated conditioned responding to the cue. Here we report two experiments in which potential parallels between the context specificity of the effects of extinction and latent inhibition treatments were directly compared in a lick suppression preparation with rats. The reversed ordering of conditioning and nonreinforcement in extinction and latent inhibition designs allowed us to examine the effect of training order on the context specificity of what is learned given phasic reinforcement and nonreinforcement of a target cue. Experiment 1 found that when CS conditioning and CS nonreinforcement were administered in the same context, both extinction and latent inhibition treatments had reduced impact on test performance relative to excitatory conditioning when testing occurred outside the treatment context. Similarly, Experiment 2 found that when conditioning was administered in one context and nonreinforcement was administered in a second context, the effects of both extinction and latent inhibition treatments were attenuated when testing occurred in a neutral context relative to the context in which the CS was nonreinforced. The observed context specificity of extinction and latent inhibition treatments have both been previously reported, but not in a single experiment under otherwise identical conditions. The results of the two experiments convergently suggest that memory of nonreinforcement becomes context dependent after a cue is both reinforced and nonreinforced independent of the order of training. PMID:26100525

  7. The effect of morphine on fear extinction in rats.

    PubMed

    Morris, M D; Gebhart, G F

    1978-05-31

    Rats were trained on an appetitive discretetrial discriminated-punishment task in which they learned to suppress responding when an intense flashing light predicting punishment was present and to respond rapidly on trials when the flashing light was absent. Once animals were performing discriminatively, 0.75, 3.0, or 6.0 mg/kg of morphine (base) was administered and a fear extinction session consisting of 60 nonshocked presentations of the flashing light was given. Two saline control groups, one that received fear extinction and one that did not, were also included in the experiment. On the day following fear extinction, all rats were tested in the undrugged state on the discriminated punishment problem, but without shock. The rats receiving 3.0 and 6.0 mg/kg of morphine before the fear extinction session were suppressed by the flashing light more than the saline extinction group or the 0.75 mg/kg morphine treatment group. Moreover, the two higher dose morphine groups were suppressed as readily as the saline group that received no fear extinction. These results are attributed to the antiemotionality effects of morphine.

  8. The effect of mindfulness on extinction and behavioral resurgence.

    PubMed

    McHugh, Louise; Procter, Jonathan; Herzog, Michaela; Schock, Anne-Kathrin; Reed, Phil

    2012-12-01

    In the present experiments, we investigated the effects of mindfulness on behavioral extinction and resurgence. Participants received instrumental training; either they received FI training (Experiment 1), or they were trained to emit high rates and low rates of response via exposure to a multiple VR yoked-VI schedule prior to exposure to a multiple FI FI schedule in order to alter their rates of responding learned during Experiment 2. Participants were then exposed to either a focused- (mindfulness) or an unfocused-attention induction task. All participants were finally exposed to an extinction schedule in order to determine whether a mindfulness induction task presented immediately prior to extinction training affected extinction (Experiment 1) and behavioral resurgence (Experiment 2). During the extinction phase, the rates of responding were higher in the control group than in the mindfulness group, indicating that the mindfulness group was more sensitive to the contingencies and, thus, their prior performance extinguished more readily (Experiment 1). Moreover, rates of response in the extinction components less precisely reflected previous training in the mindfulness group, suggesting less resurgence of past behaviors after the mindfulness induction (Experiment 2).

  9. Comparing the context specificity of extinction and latent inhibition.

    PubMed

    Miller, Ralph R; Laborda, Mario A; Polack, Cody W; Miguez, Gonzalo

    2015-12-01

    Exposure to a cue alone either before (i.e., latent inhibition treatment) or after (i.e., extinction) the cue is paired with an unconditioned stimulus results in attenuated conditioned responding to the cue. Here we report two experiments in which potential parallels between the context specificity of the effects of extinction and latent inhibition treatments were directly compared in a lick suppression preparation with rats. The reversed ordering of conditioning and nonreinforcement in extinction and latent inhibition designs allowed us to examine the effect of training order on the context specificity of what is learned given phasic reinforcement and nonreinforcement of a target cue. Experiment 1 revealed that when conditioned-stimulus (CS) conditioning and CS nonreinforcement were administered in the same context, both extinction and latent inhibition treatments had reduced impacts on test performance, relative to excitatory conditioning when testing occurred outside the treatment context. Similarly, Experiment 2 showed that when conditioning was administered in one context and nonreinforcement was administered in a second context, the effects of both extinction and latent inhibition treatments were attenuated when testing occurred in a neutral context, relative to the context in which the CS was nonreinforced. The observed context specificity of extinction and latent inhibition treatments has been previously reported in both cases, but not in a single experiment under otherwise identical conditions. The results of the two experiments convergently suggest that memory of nonreinforcement becomes context dependent after a cue is both reinforced and nonreinforced, independent of the order of training.

  10. Mass Extinctions in Earth's History

    NASA Astrophysics Data System (ADS)

    Ward, P. D.

    2002-12-01

    Mass extinctions are short intervals of elevated species death. Possible causes of Earth's mass extinctions are both external (astronomical) and internal (tectonic and biotic changes from planetary mechanisms). Paleontologists have identified five "major" mass extinctions (>50 die-off in less than a million years) and more than 20 other minor events over the past 550 million years. Earlier major extinction events undoubtedly also occurred, but we have no fossil record; these were probably associated with, for example, the early heavy bombardment that cleared out the solar system, the advent of oxygen in the atmosphere, and various "snowball Earth" events. Mass extinctions are viewed as both destructive (species death ) and constructive, in that they allow evolutionary innovation in the wake of species disappearances. From an astrobiological perspective, mass extinctions must be considered as able both to reduce biodiversity and even potentially end life on any planet. Of the five major mass extinctions identified on Earth, only one (the Cretaceous/Tertiary event 65 million years ago that famously killed off the dinosaurs ) is unambiguously related to the impact of an asteroid or comet ( 10-km diameter). The Permian/Triassic (250 Myr ago) and Triassic/Jurassic (202 Myr ago) events are now the center of debate between those favoring impact and those suggesting large volume flooding by basaltic lavas. The final two events, Ordovician (440 Myr ago) and Devonian (370 Myr ago) have no accepted causal mechanisms.

  11. Extinction in young massive clusters

    NASA Astrophysics Data System (ADS)

    De Marchi, Guido; Panagia, Nino

    2016-01-01

    Up to ages of ~100 Myr, massive clusters are still swamped in large amounts of gas and dust, causing considerable and uneven levels of extinction. At the same time, large grains (ices?) produced by type II supernovae profoundly alter the interstellar medium (ISM), thus resulting in extinction properties very different from those of the diffuse ISM. To obtain physically meaningful parameters of stars (luminosities, effective temperatures, masses, ages, etc.) we must understand and measure the local extinction law. We have developed a powerful method to unambiguously determine the extinction law everywhere across a cluster field, using multi-band photometry of red giant stars belonging to the red clump (RC) and are applying it to young massive clusters in the Local Group. In the Large Magellanic Cloud, with about 20 RC stars per arcmin2, for each field we can easily derive an accurate extinction curve over the entire wavelength range of the photometry. As an example, we present the extinction law of the Tarantula nebula (30 Dor) based on thousands of stars observed as part of the Hubble Tarantula Treasury Project. We discuss how the incautious adoption of the Milky Way extinction law in the analysis of massive star forming regions may lead to serious underestimates of the fluxes and of the star formation rates by factors of 2 or more.

  12. 5 CFR 630.503 - Leave from former leave systems.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Leave from former leave systems. 630.503... AND LEAVE Recredit of Leave § 630.503 Leave from former leave systems. An employee who earned leave under the leave acts of 1936 or any other leave system merged under subchapter I of chapter 63 of...

  13. Infant Contingency/Extinction Performance after Observing Partial Reinforcement

    ERIC Educational Resources Information Center

    Weir, Catherine; Toland, Cynthia; King, Rose Ann; Martin, Lisa Maas

    2005-01-01

    Social information gathering by infants 6 and 12 months old was examined as a foundation for later social learning that may be uniquely human. Infant performance on a contingency/extinction task was studied following a caregiver demonstration of the contingency on varied reinforcement schedules. Infants who observed caregivers receive any…

  14. Extinction Circuits for Fear and Addiction Overlap in Prefrontal Cortex

    ERIC Educational Resources Information Center

    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…

  15. Activation of orexin/hypocretin neurons is associated with individual differences in cued fear extinction.

    PubMed

    Sharko, Amanda C; Fadel, Jim R; Kaigler, Kris F; Wilson, Marlene A

    2017-09-01

    Identifying the neurobiological mechanisms that underlie differential sensitivity to stress is critical for understanding the development and expression of stress-induced disorders, such as post-traumatic stress disorder (PTSD). Preclinical studies have suggested that rodents display different phenotypes associated with extinction of Pavlovian conditioned fear responses, with some rodent populations being resistant to extinction. An emerging literature also suggests a role for orexins in the consolidation processes associated with fear learning and extinction. To examine the possibility that the orexin system might be involved in individual differences in fear extinction, we used a Pavlovian conditioning paradigm in outbred Long-Evans rats. Rats showed significant variability in the extinction of cue-conditioned freezing and extinction recall, and animals were divided into groups based on their extinction profiles based on a median split of percent freezing behavior during repeated exposure to the conditioned cue. Animals resistant to extinction (high freezers) showed more freezing during repeated cue presentations during the within trial and between trial extinction sessions compared with the group showing significant extinction (low freezers), although there were no differences between these groups in freezing upon return to the conditioned context or during the conditioning session. Following the extinction recall session, activation of orexin neurons was determined using dual label immunohistochemistry for cFos in orexin positive neurons in the hypothalamus. Individual differences in the extinction of cue conditioned fear were associated with differential activation of hypothalamic orexin neurons. Animals showing poor extinction of cue-induced freezing (high freezers) had significantly greater percentage of orexin neurons with Fos in the medial hypothalamus than animals displaying significant extinction and good extinction recall (low freezers). Further, the

  16. New theories about ancient extinctions

    USGS Publications Warehouse

    Spall, H.

    1986-01-01

    But all this may be changing. Mass extinctions have been very much in the news in the last few years, triggered in large part by the proposal that the extinction of the dinosaurs and marine animals was caused by a catastrophic collision between the Earth and an extra-terrestrial body (bolide). Recently an equally contentious suggestion has been made that mass extinctions have swept the Earth every 26 to 31 million years for at least the last 250 million years-caused by encounters with some kind of extra-terrestrial object such as one of the asteroids or the comets. 

  17. Hunger Promotes Fear Extinction by Activation of an Amygdala Microcircuit

    PubMed Central

    Verma, Dilip; Wood, James; Lach, Gilliard; Herzog, Herbert; Sperk, Guenther; Tasan, Ramon

    2016-01-01

    Emotions control evolutionarily-conserved behavior that is central to survival in a natural environment. Imbalance within emotional circuitries, however, may result in malfunction and manifestation of anxiety disorders. Thus, a better understanding of emotional processes and, in particular, the interaction of the networks involved is of considerable clinical relevance. Although neurobiological substrates of emotionally controlled circuitries are increasingly evident, their mutual influences are not. To investigate interactions between hunger and fear, we performed Pavlovian fear conditioning in fasted wild-type mice and in mice with genetic modification of a feeding-related gene. Furthermore, we analyzed in these mice the electrophysiological microcircuits underlying fear extinction. Short-term fasting before fear acquisition specifically impaired long-term fear memory, whereas fasting before fear extinction facilitated extinction learning. Furthermore, genetic deletion of the Y4 receptor reduced appetite and completely impaired fear extinction, a phenomenon that was rescued by fasting. A marked increase in feed-forward inhibition between the basolateral and central amygdala has been proposed as a synaptic correlate of fear extinction and involves activation of the medial intercalated cells. This form of plasticity was lost in Y4KO mice. Fasting before extinction learning, however, resulted in specific activation of the medial intercalated neurons and re-established the enhancement of feed-forward inhibition in this amygdala microcircuit of Y4KO mice. Hence, consolidation of fear and extinction memories is differentially regulated by hunger, suggesting that fasting and modification of feeding-related genes could augment the effectiveness of exposure therapy and provide novel drug targets for treatment of anxiety disorders. PMID:26062787

  18. Hunger Promotes Fear Extinction by Activation of an Amygdala Microcircuit.

    PubMed

    Verma, Dilip; Wood, James; Lach, Gilliard; Herzog, Herbert; Sperk, Guenther; Tasan, Ramon

    2016-01-01

    Emotions control evolutionarily-conserved behavior that is central to survival in a natural environment. Imbalance within emotional circuitries, however, may result in malfunction and manifestation of anxiety disorders. Thus, a better understanding of emotional processes and, in particular, the interaction of the networks involved is of considerable clinical relevance. Although neurobiological substrates of emotionally controlled circuitries are increasingly evident, their mutual influences are not. To investigate interactions between hunger and fear, we performed Pavlovian fear conditioning in fasted wild-type mice and in mice with genetic modification of a feeding-related gene. Furthermore, we analyzed in these mice the electrophysiological microcircuits underlying fear extinction. Short-term fasting before fear acquisition specifically impaired long-term fear memory, whereas fasting before fear extinction facilitated extinction learning. Furthermore, genetic deletion of the Y4 receptor reduced appetite and completely impaired fear extinction, a phenomenon that was rescued by fasting. A marked increase in feed-forward inhibition between the basolateral and central amygdala has been proposed as a synaptic correlate of fear extinction and involves activation of the medial intercalated cells. This form of plasticity was lost in Y4KO mice. Fasting before extinction learning, however, resulted in specific activation of the medial intercalated neurons and re-established the enhancement of feed-forward inhibition in this amygdala microcircuit of Y4KO mice. Hence, consolidation of fear and extinction memories is differentially regulated by hunger, suggesting that fasting and modification of feeding-related genes could augment the effectiveness of exposure therapy and provide novel drug targets for treatment of anxiety disorders.

  19. Spatial memory extinction: a c-Fos protein mapping study.

    PubMed

    Méndez-Couz, M; Conejo, N M; Vallejo, G; Arias, J L

    2014-03-01

    While the neuronal basis of spatial memory consolidation has been thoroughly studied, the substrates mediating the process of extinction remain largely unknown. This study aimed to evaluate the functional contribution of selected brain regions during the extinction of a previously acquired spatial memory task in the Morris water maze. For that purpose, we used adult male Wistar rats trained in a spatial reference memory task. Learning-related changes in c-Fos inmunoreactive cells after training were evaluated in cortical and subcortical regions. Results show that removal of the hidden platform in the water maze induced extinction of the previously reinforced escape behavior after 16 trials, without spontaneous recovery 24h later. Extinction was related with significantly higher numbers of c-Fos positive nuclei in amygdala nuclei and prefrontal cortex. On the other hand, the lateral mammillary bodies showed higher number of c-Fos positive cells than the control group. Therefore, in contrast with the results obtained in studies of classical conditioning, we show the involvement of diencephalic structures mediating this kind of learning. In summary, our findings suggest that medial prefrontal cortex, the amygdala complex and diencephalic structures like the lateral mammillary nuclei are relevant for the extinction of spatial memory.

  20. Issues in the Extinction of Specific Stimulus-Outcome Associations in Pavlovian Conditioning

    PubMed Central

    Delamater, Andrew R.

    2012-01-01

    This paper reviews a variety of studies designed to examine the effects of extinction upon control by specific stimulus-outcome (S-O) associations in Pavlovian conditioning. Studies conducted with rats in a magazine approach conditioning paradigm have shown that control by specific S-O associations is normally unaffected by extinction treatments, although other aspects of conditioned responding seem affected in a more enduring way. However, recent work suggests that extinction can undermine control by such associations if it is administered after the conditioned stimulus is weakly encoded. The results from these studies suggest that it may be important to consider multiple response systems in assessing the impact of extinction. Studies conducted with the flavor preference learning paradigm in rats also show that specific S-O associations can be undermined by procedures that involve presenting a flavor cue in the absence of its associated nutrient. These findings provide no support for the view that flavor preference learning necessarily entails some unique learning process that differs from more conventional processes. As in other situations, some of these effects likely involve a masking process, but the extent to which masking or true associative weakening occurs in extinction more generally is a topic that is not well understood. Finally, we present some data to suggest that extinction also involves conditional “occasion-setting” control by contextual cues. Special procedures are recommended in assessing such learning when the goal is to distinguish this form of learning from other more conventional mechanisms of extinction. PMID:22465262

  1. Issues in the extinction of specific stimulus-outcome associations in Pavlovian conditioning.

    PubMed

    Delamater, Andrew R

    2012-05-01

    This paper reviews a variety of studies designed to examine the effects of extinction upon control by specific stimulus-outcome (S-O) associations in Pavlovian conditioning. Studies conducted with rats in a magazine approach conditioning paradigm have shown that control by specific S-O associations is normally unaffected by extinction treatments, although other aspects of conditioned responding seem affected in a more enduring way. However, recent work suggests that extinction can undermine control by such associations if it is administered after the conditioned stimulus is weakly encoded. The results from these studies suggest that it may be important to consider multiple response systems in assessing the impact of extinction. Studies conducted with the flavor preference learning paradigm in rats also show that specific S-O associations can be undermined by procedures that involve presenting a flavor cue in the absence of its associated nutrient. These findings provide no support for the view that flavor preference learning necessarily entails some unique learning process that differs from more conventional processes. As in other situations, some of these effects likely involve a masking process, but the extent to which masking or true associative weakening occurs in extinction more generally is a topic that is not well understood. Finally, we present some data to suggest that extinction also involves conditional "occasion-setting" control by contextual cues. Special procedures are recommended in assessing such learning when the goal is to distinguish this form of learning from other more conventional mechanisms of extinction.

  2. De-scenting Extinction: The Promise of De-extinction May Hasten Continuing Extinctions.

    PubMed

    Campagna, Claudio; Guevara, Daniel; Le Boeuf, Bernard

    2017-07-01

    Among the most egregious and discouraging problems of conservation is the rapidly escalating human-caused species extinction rate. "De-extinction" refers to the application of certain cutting-edge techniques for the supposed recovery of lost species and gives the impression that scientists, enlightened and empowered by the miracles of technology, are coming to the rescue. "De-extinction" is the latest example of a long play of language that has given conservation efforts a tragically false sense of accomplishment and has worsened the conservation crisis. De-extinction is the tip of an intellectual iceberg that sits atop of a host of profoundly questionable value systems, expectations, attitudes, and priorities that elude and bewitch critical reflection. It gives the impression that extinction is reversible and, thus, diminishes the gravity of the human annihilation of species. Here, we examine how the language of de-extinction influences attitudes, shapes thoughts and imagination, and creates ethical blindness. The language developing around "de-extinction" reveals what is in fact a profound intellectual crisis at the foundation of conservation. The underlying challenge is to find the language that will articulate and inspire the radical and indispensable change needed to come to grips with the value of nature. © 2017 The Hastings Center.

  3. Extinction under a Behavioral Microscope: Isolating the Sources of Decline in Operant Response Rate

    PubMed Central

    Cheung, Timothy H C; Neisewander, Janet L; Sanabria, Federico

    2012-01-01

    Extinction performance is often used to assess underlying psychological processes without the interference of reinforcement. For example, in the extinction/reinstatement paradigm, motivation to seek drug is assessed by measuring responding elicited by drug-associated cues without drug reinforcement. Nonetheless, extinction performance is governed by several psychological processes that involve motivation, memory, learning, and motoric functions. These processes are confounded when overall response rate is used to measure performance. Based on evidence that operant responding occurs in bouts, this paper proposes an analytic procedure that separates extinction performance into several behavioral components: 1) the baseline bout initiation rate, within-bout response rate, and bout length at the onset of extinction; 2) their rates of decay during extinction; 3) the time between extinction onset and the decline of responding; 4) the asymptotic response rate at the end of extinction; 5) the refractory period after each response. Data that illustrate the goodness of fit of this analytic model are presented. This paper also describes procedures to 1) isolate behavioral components contributing to extinction performance; 2) make inferences about experimental effects on these components. This microscopic behavioral analysis allows the mapping of different psychological processes to distinct behavioral components implicated in extinction performance, which may further our understanding of the psychological effects of neurobiological treatments. PMID:22425782

  4. Extinction under a behavioral microscope: isolating the sources of decline in operant response rate.

    PubMed

    Cheung, Timothy H C; Neisewander, Janet L; Sanabria, Federico

    2012-05-01

    Extinction performance is often used to assess underlying psychological processes without the interference of reinforcement. For example, in the extinction/reinstatement paradigm, motivation to seek drug is assessed by measuring responding elicited by drug-associated cues without drug reinforcement. However, extinction performance is governed by several psychological processes that involve motivation, memory, learning, and motoric functions. These processes are confounded when overall response rate is used to measure performance. Based on evidence that operant responding occurs in bouts, this paper proposes an analytic procedure that separates extinction performance into several behavioral components: (1-3) the baseline bout initiation rate, within-bout response rate, and bout length at the onset of extinction; (4-6) their rates of decay during extinction; (7) the time between extinction onset and the decline of responding; (8) the asymptotic response rate at the end of extinction; (9) the refractory period after each response. Data that illustrate the goodness of fit of this analytic model are presented. This paper also describes procedures to isolate behavioral components contributing to extinction performance and make inferences about experimental effects on these components. This microscopic behavioral analysis allows the mapping of different psychological processes to distinct behavioral components implicated in extinction performance, which may further our understanding of the psychological effects of neurobiological treatments.

  5. Effects of a context shift and multiple context extinction on reactivity to alcohol cues.

    PubMed

    MacKillop, James; Lisman, Stephen A

    2008-08-01

    Cue exposure treatment (CET) attempts to reduce the influence of conditioned substance cues on addictive behavior via extinction, but has received only modest empirical support in clinical trials. This may be because extinction learning appears to be context dependent and a change in context may result in a return of conditioned responding (i.e., renewal), although this has received only limited empirical examination. The current study used a 4-session laboratory analogue of CET to examine whether a change in context following 3 sessions of alcohol cue exposure with response prevention would result in renewal of conditioned responding. In addition, this study examined whether conducting extinction in multiple contexts would attenuate renewal of conditioned responding. In one-way between-subjects design, 73 heavy drinkers (71% men) were randomized to 3 conditions: (a) single context extinction (extinction to alcohol cues in the same context for 3 sessions followed by a context shift at the fourth session), (b) multiple context extinction (extinction to alcohol cues in different contexts each day for all 4 sessions), and (c) pseudoextinction control condition (exposure to neutral cues in the same context for 3 sessions followed by exposure to alcohol cues at the fourth session). The results revealed the predicted cue reactivity and extinction effects, but the hypotheses that a context shift would generate renewed cue reactivity and that multiple contexts would enhance extinction were not supported. Methodological aspects of the study and the need for parametric data on the context dependency of extinction to alcohol cues are discussed.

  6. Orbitofrontal cortex inactivation impairs between- but not within-session Pavlovian extinction: an associative analysis.

    PubMed

    Panayi, Marios C; Killcross, Simon

    2014-02-01

    The orbitofrontal cortex (OFC) is argued to be the neural locus of Pavlovian outcome expectancies. Reinforcement learning theories argue that extinction learning in Pavlovian procedures is caused by the discrepancy between the expected value of the outcome (US) that is elicited by a predictive stimulus (CS), and the lack of experienced US. If the OFC represents Pavlovian outcome expectancies that are necessary for extinction learning, then disrupting OFC function prior to extinction training should impair extinction learning. This was tested. In experiment 1, Long Evans rats received infusions of saline or muscimol targeting the lateral OFC prior to three appetitive Pavlovian extinction sessions. Muscimol infused into the OFC disrupted between-session but not within-session extinction behaviour. This finding was not due to muscimol infusions disrupting the memory consolidation process per se as there was no effect of muscimol infusion when administered immediately post session (experiment 2). These findings support a role for the OFC in representing outcome expectancies that are necessary for learning. A number of ways in which disrupting outcome expectancy information might block learning will be discussed in the context of traditional associative learning theories and the associative structures they depend on.

  7. What Caused the Mass Extinction?

    ERIC Educational Resources Information Center

    Alvarez, Walter; And Others

    1990-01-01

    Presented are the arguments of two different points of view on the mass extinction of the dinosaurs. Evidence of extraterrestrial impact theory and massive volcanic eruption theory are discussed. (CW)

  8. What Caused the Mass Extinction?

    ERIC Educational Resources Information Center

    Alvarez, Walter; And Others

    1990-01-01

    Presented are the arguments of two different points of view on the mass extinction of the dinosaurs. Evidence of extraterrestrial impact theory and massive volcanic eruption theory are discussed. (CW)

  9. Investigation of ultraviolet interstellar extinction

    NASA Technical Reports Server (NTRS)

    Payne, C.; Haramundanis, K. L.

    1973-01-01

    Results concerning interstellar extinction in the ultraviolet are reported. These results were initially obtained by using data from main-sequence stars and were extended to include supergiants and emission stars. The principal finding of the analysis of ultraviolet extinction is not only that it is wavelength dependent, but that if changes with galactic longitude in the U3 passband (lambda sub eff = 1621 A); it does not change significantly in the U2 passband (lambda sub eff = 2308 A). Where data are available in the U4 passband (lambda sub eff = 1537 A), they confirm the rapid rise of extinction in the ultraviolet found by other investigators. However, in all cases, emission stars must be used with great caution. It is important to realize that while extinction continues to rise toward shorter wavelengths in the ultraviolet, including the shortest ultraviolet wavelengths measured (1100 A), it no longer plays an important role in the X-ray region (50 A).

  10. Investigation of ultraviolet interstellar extinction

    NASA Technical Reports Server (NTRS)

    Payne-Gaposchkin, C.; Haramundanis, K. L.

    1973-01-01

    The progress made during the past six months in utilizing Celescope OAO-2 data in a study of extinction is reported along with conclusions drawn from each inquiry. Areas recommended for further investigation are indicated.

  11. Updating Martin's global extinction model

    NASA Astrophysics Data System (ADS)

    Gillespie, Richard

    2008-12-01

    Australia has been cited as a weak link in anthropogenic models of megafauna extinction, but recent work suggests instead that the evidence for rapid extinction shortly after human arrival is robust. The global model is revisited, based on the contention that late Pleistocene megafauna extinctions took place rapidly on islands, and some islands (such as Australia and the Americas) are much larger than others. Modern dating methods are increasingly able to refine chronologies, and careful scrutiny suggests that hundreds of dates should be deleted from archives. An updated summary of results from New Zealand, North America and Australia is presented, with a brief discussion on why temperate refugia offering protection from climate change ultimately did not work, strongly supporting the global extinction hypothesis pioneered by Paul Martin.

  12. Transgenic Inhibition of Neuronal Protein Kinase A Activity Facilitates Fear Extinction

    PubMed Central

    Isiegas, Carolina; Park, Alice; Kandel, Eric R.; Abel, Ted; Lattal, K. Matthew

    2010-01-01

    Much is known about the neurobiology of memory storage for learned fear. In contrast, the molecular mechanisms underlying extinction of fear memory are just beginning to be delineated. Here, we investigate the role of protein kinase A (PKA) in extinction of memory for contextual fear by using conventional and temporally regulated transgenic approaches that allow us to inhibit PKA activity in neurons within brain regions thought to be involved in extinction. Strikingly, reduction of PKA activity facilitated the development of extinction, without interfering with storage of the original fear memory. Moreover, inhibition of PKA facilitated extinction of both recent and remote contextual fear memories. The finding that PKA, which is required for the acquisition of fear memory, is a constraint for extinction provides the first genetic support for the idea that fear extinction is itself a genuine learning process with its own specific molecular requirements, rather than simply the erasure of a previously learned process. Further, these experiments represent the first genetic evidence that protein kinases may be constraints for the extinction of fear. PMID:17151273

  13. Magnetic reversals and mass extinctions

    NASA Technical Reports Server (NTRS)

    Raup, D. M.

    1985-01-01

    The results of a study of reversals of the earth's magnetic field over the past 165 Myr are presented. A stationary periodicity of 30 Myr emerges which predicts pulses of increased reversal activity centered at 10, 40, 70, . . . Myr before the present. The correlation between the reversal intensity and biological extinctions is examined, and a nontrivial discrepancy is found between the magnetic and extinction periodicity.

  14. Magnetic reversals and mass extinctions

    NASA Technical Reports Server (NTRS)

    Raup, D. M.

    1985-01-01

    The results of a study of reversals of the earth's magnetic field over the past 165 Myr are presented. A stationary periodicity of 30 Myr emerges which predicts pulses of increased reversal activity centered at 10, 40, 70, . . . Myr before the present. The correlation between the reversal intensity and biological extinctions is examined, and a nontrivial discrepancy is found between the magnetic and extinction periodicity.

  15. The Sixth Great Mass Extinction

    ERIC Educational Resources Information Center

    Wagler, Ron

    2012-01-01

    Five past great mass extinctions have occurred during Earth's history. Humanity is currently in the midst of a sixth, human-induced great mass extinction of plant and animal life (e.g., Alroy 2008; Jackson 2008; Lewis 2006; McDaniel and Borton 2002; Rockstrom et al. 2009; Rohr et al. 2008; Steffen, Crutzen, and McNeill 2007; Thomas et al. 2004;…

  16. Series cell light extinction monitor

    DOEpatents

    Novick, Vincent J.

    1990-01-01

    A method and apparatus for using the light extinction measurements from two or more light cells positioned along a gasflow chamber in which the gas volumetric rate is known to determine particle number concentration and mass concentration of an aerosol independent of extinction coefficient and to determine estimates for particle size and mass concentrations. The invention is independent of particle size. This invention has application to measurements made during a severe nuclear reactor fuel damage test.

  17. The Sixth Great Mass Extinction

    ERIC Educational Resources Information Center

    Wagler, Ron

    2012-01-01

    Five past great mass extinctions have occurred during Earth's history. Humanity is currently in the midst of a sixth, human-induced great mass extinction of plant and animal life (e.g., Alroy 2008; Jackson 2008; Lewis 2006; McDaniel and Borton 2002; Rockstrom et al. 2009; Rohr et al. 2008; Steffen, Crutzen, and McNeill 2007; Thomas et al. 2004;…

  18. Measuring Galactic Extinction: A Test

    NASA Astrophysics Data System (ADS)

    Arce, Héctor G.; Goodman, Alyssa A.

    1999-02-01

    We test the recently published all-sky reddening map of Schlegel, Finkbeiner, & Davis (hereafter SFD) using the extinction study of a region in the Taurus dark cloud complex by Arce & Goodman (hereafter AG). In their study, AG use four different techniques to measure the amount and structure of the extinction toward Taurus, and all four techniques agree very well. Thus, we believe that the AG results are a truthful representation of the extinction in the region and can be used to test the reliability of the SFD reddening map. The results of our test show that the SFD all-sky reddening map, which is based on data from COBE/DIRBE and IRAS/ISSA, overestimates the reddening by a factor of 1.3-1.5 in regions of smooth extinction with AV>0.5 mag. In some regions of steep extinction gradients, the SFD map underestimates the reddening value, probably because of its low spatial resolution. We expect that the astronomical community will be using the SFD reddening map extensively. We offer this Letter as a cautionary note about using the SFD map in regions of high extinction (AV>0.5 mag), since it might not be giving accurate reddening values there.

  19. Extinction, relapse, and behavioral momentum.

    PubMed

    Podlesnik, Christopher A; Shahan, Timothy A

    2010-05-01

    Previous experiments on behavioral momentum have shown that relative resistance to extinction of operant behavior in the presence of a discriminative stimulus depends upon the baseline rate or magnitude of reinforcement associated with that stimulus (i.e., the Pavlovian stimulus-reinforcer relation). Recently, we have shown that relapse of operant behavior in reinstatement, resurgence, and context renewal preparations also is a function of baseline stimulus-reinforcer relations. In this paper we present new data examining the role of baseline stimulus-reinforcer relations on resistance to extinction and relapse using a variety of baseline training conditions and relapse operations. Furthermore, we evaluate the adequacy of a behavioral momentum based model in accounting for the results. The model suggests that relapse occurs as a result of a decrease in the disruptive impact of extinction precipitated by a change in circumstances associated with extinction, and that the degree of relapse is a function of the pre-extinction baseline Pavlovian stimulus-reinforcer relation. Across experiments, relative resistance to extinction and relapse were greater in the presence of stimuli associated with more favorable conditions of reinforcement and were positively related to one another. In addition, the model did a good job in accounting for these effects. Thus, behavioral momentum theory may provide a useful quantitative approach for characterizing how differential reinforcement conditions contribute to relapse of operant behavior.

  20. Extinction, Relapse, and Behavioral Momentum

    PubMed Central

    Podlesnik, Christopher A.; Shahan, Timothy A.

    2010-01-01

    Previous experiments on behavioral momentum have shown that relative resistance to extinction of operant behavior in the presence of a discriminative stimulus depends upon the baseline rate or magnitude of reinforcement associated with that stimulus (i.e., the Pavlovian stimulus-reinforcer relation). Recently, we have shown that relapse of operant behavior in reinstatement, resurgence, and context renewal preparations also is a function of baseline stimulus-reinforcer relations. In this paper we present new data examining the role of baseline stimulus-reinforcer relations on resistance to extinction and relapse using a variety of baseline training conditions and relapse operations. Furthermore, we evaluate the adequacy of a behavioral-momentum based model in accounting for the results. The model suggests that relapse occurs as a result of a decrease in the disruptive impact of extinction precipitated by a change in circumstances associated with extinction, and that the degree of relapse is a function of the pre-extinction baseline Pavlovian stimulus-reinforcer relation. Across experiments, relative resistance to extinction and relapse were greater in the presence of stimuli associated with more favorable conditions of reinforcement and were positively related to one another. In addition, the model did a good job in accounting for these effects. Thus, behavioral momentum theory may provide a useful quantitative approach for characterizing how differential reinforcement conditions contribute to relapse of operant behavior. PMID:20152889

  1. Enhanced Extinction of Aversive Memories by High-Frequency Stimulation of the Rat Infralimbic Cortex

    PubMed Central

    Maroun, Mouna; Kavushansky, Alexandra; Holmes, Andrew; Wellman, Cara; Motanis, Helen

    2012-01-01

    Electrical stimulation of the rodent medial prefrontal cortex (mPFC), including the infralimbic cortex (IL), immediately prior to or during fear extinction training facilitates extinction memory. Here we examined the effects of high-frequency stimulation (HFS) of the rat IL either prior to conditioning or following retrieval of the conditioned memory, on extinction of Pavlovian fear and conditioned taste aversion (CTA). IL-HFS applied immediately after fear memory retrieval, but not three hours after retrieval or prior to conditioning, subsequently reduced freezing during fear extinction. Similarly, IL-HFS given immediately, but not three hours after, retrieval of a CTA memory reduced aversion during extinction. These data indicate that HFS of the IL may be an effective method for reducing both learned fear and learned aversion. PMID:22586453

  2. Species, extinct before we know them?

    PubMed

    Lees, Alexander C; Pimm, Stuart L

    2015-03-02

    Species are going extinct rapidly, while taxonomic catalogues are still incomplete for even the best-known taxa. Intensive fieldwork is finding species so rare and threatened that some become extinct within years of discovery. Recent bird extinctions in Brazil's coastal forests suggest that some species may have gone extinct before we knew of their existence. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Prior cocaine exposure disrupts extinction of fear conditioning

    PubMed Central

    Burke, Kathryn A.; Franz, Theresa M.; Gugsa, Nishan; Schoenbaum, Geoffrey

    2008-01-01

    Psychostimulant exposure has been shown to cause molecular and cellular changes in prefrontal cortex. It has been hypothesized that these drug-induced changes might affect the operation of prefrontal-limbic circuits, disrupting their normal role in controlling behavior and thereby leading to compulsive drug-seeking. To test this hypothesis, we tested cocaine-treated rats in a fear conditioning, inflation, and extinction task, known to depend on medial prefrontal cortex and amygdala. Cocaine-treated rats conditioned and inflated similar to saline controls but displayed slower extinction learning. These results support the hypothesis that control processes in the medial prefrontal cortex are impaired by cocaine exposure. PMID:16847305

  4. Thermal Transgressions and Phanerozoic Extinctions

    NASA Astrophysics Data System (ADS)

    Worsley, T. R.; Kidder, D. L.

    2007-12-01

    A number of significant Phanerozoic extinctions are associated with marine transgressions that were probably driven by rapid ocean warming. The conditions associated with what we call thermal transgressions are extremely stressful to life on Earth. The Earth system setting associated with end-Permian extinction exemplifies an end-member case of our model. The conditions favoring extreme warmth and sea-level increases driven by thermal expansion are also conducive to changes in ocean circulation that foster widespread anoxia and sulfidic subsurface ocean waters. Equable climates are characterized by reduced wind shear and weak surface ocean circulation. Late Permian and Early Triassic thermohaline circulation differs considerably from today's world, with minimal polar sinking and intensified mid-latitude sinking that delivers sulfate from shallow evaporative areas to deeper water where it is reduced to sulfide. Reduced nutrient input to oceans from land at many of the extinction intervals results from diminished silicate weathering and weakened delivery of iron via eolian dust. The falloff in iron-bearing dust leads to minimal nitrate production, weakening food webs and rendering faunas and floras more susceptible to extinction when stressed. Factors such as heat, anoxia, ocean acidification, hypercapnia, and hydrogen sulfide poisoning would significantly affect these biotas. Intervals of tectonic quiescence set up preconditions favoring extinctions. Reductions in chemical silicate weathering lead to carbon dioxide buildup, oxygen drawdown, nutrient depletion, wind and ocean current abatement, long-term global warming, and ocean acidification. The effects of extinction triggers such as large igneous provinces, bolide impacts, and episodes of sudden methane release are more potent against the backdrop of our proposed preconditions. Extinctions that have characteristics we call for in the thermal transgressions include the Early Cambrian Sinsk event, as well as

  5. The stratigraphy of mass extinction

    NASA Astrophysics Data System (ADS)

    Holland, Steven

    2015-04-01

    The discovery of the end-Cretaceous bolide impact and the recognition of mass extinctions through taxonomic compendia triggered keen interest in the stratigraphic pattern of species extinctions. A principal question has been whether patterns of fossil occurrence indicate gradual, stepwise, pulsed, or instantaneous extinction. Based on principles of sequence stratigraphy, marine ecology, and evolution, numerical models of fossil occurrences in stratigraphic sections indicate that the last occurrence of fossils does not generally indicate the time of extinction but is instead controlled by stratigraphic architecture. These models have been confirmed in multiple field studies from different sedimentary basins of different ages. These models identify several distinct processes controlling the last occurrence of fossils. Anything that lowers the probability of collection of a species, such as peak abundance or environmental tolerance, causes the last occurrence to be shifted backward in time relative to the time of extinction. Sequence-bounding subaerial unconformities generally also force the last occurrence backward in time, except in the case of reworking, which may place fossil remains in rocks younger than the time of extinction. Unconformities also cause last occurrences of multiple species to be clustered as a result of the hiatus. Surfaces of abrupt facies change, such as flooding surfaces and surfaces of forced regression, also cause last occurrences to be clustered, with such clustering reflecting the environmental preferences of species. Stratigraphic condensation can also cause clustering of last occurrences. All of these surfaces - subaerial unconformities, flooding surfaces, surfaces of forced regression, and condensed horizons - have highly predictable positions with depositional sequences. Thus, it is the normal expectation that last occurrences should be clustered in the fossil record, that these clusters should occur in stratigraphically predictable

  6. β-Adrenoceptor Blockade in the Basolateral Amygdala, But Not the Medial Prefrontal Cortex, Rescues the Immediate Extinction Deficit.

    PubMed

    Giustino, Thomas F; Seemann, Jocelyn R; Acca, Gillian M; Goode, Travis D; Fitzgerald, Paul J; Maren, Stephen

    2017-05-02

    Early psychological interventions, such as exposure therapy, rely on extinction learning to reduce the development of stress- and trauma-related disorders. However, recent research suggests that extinction often fails to reduce fear when administered soon after trauma. This immediate extinction deficit (IED) may be due to stress-induced dysregulation of neural circuits involved in extinction learning. We have shown that systemic β-adrenoceptor blockade with propranolol rescues the IED, but impairs delayed extinction. Here we sought to determine the neural locus of these effects. Rats underwent auditory fear conditioning and then received either immediate (30 min) or delayed (24 h) extinction training. We used bilateral intracranial infusions of propranolol into either the infralimbic division of the medial prefrontal cortex (mPFC) or the basolateral amygdala (BLA) to examine the effects of β-adrenoceptor blockade on immediate and delayed extinction learning. Interestingly, intra-BLA, but not intra-mPFC, propranolol rescued the IED; animals receiving intra-BLA propranolol prior to immediate extinction showed less spontaneous recovery of fear during extinction retrieval. Importantly, this was not due to impaired consolidation of the conditioning memory. In contrast, neither intra-BLA nor intra-mPFC propranolol affected delayed extinction learning. Overall, these data contribute to a growing literature suggesting dissociable roles for key nodes in the fear extinction circuit depending on the timing of extinction relative to conditioning. These data also suggest that heightened noradrenergic activity in the BLA underlies stress-induced extinction deficits. Propranolol may be a useful adjunct to behavioral therapeutic interventions in recently traumatized individuals who are at risk for developing trauma-related disorders.Neuropsychopharmacology advance online publication, 31 May 2017; doi:10.1038/npp.2017.89.

  7. Contextual Change After Fear Acquisition Affects Conditioned Responding and the Time Course of Extinction Learning—Implications for Renewal Research

    PubMed Central

    Sjouwerman, Rachel; Niehaus, Johanna; Lonsdorf, Tina B.

    2015-01-01

    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 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 physiological (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. PMID:26696855

  8. Increases in doublecortin immunoreactivity in the dentate gyrus following extinction of heroin-seeking behavior.

    PubMed

    Hicks, Megan P; Wischerath, Kelly C; Lacrosse, Amber L; Olive, M Foster

    2012-01-01

    Adult-generated neurons in the dentate gyrus (DG) of the hippocampus play a role in various forms of learning and memory. However, adult born neurons in the DG, while still at an immature stage, exhibit unique electrophysiological properties and are also functionally implicated in learning and memory processes. We investigated the effects of extinction of drug-seeking behavior on the formation of immature neurons in the DG as assessed by quantification of doublecortin (DCX) immunoreactivity. Rats were allowed to self-administer heroin (0.03 mg/kg/infusion) for 12 days and then subjected either to 10 days of extinction training or forced abstinence. We also examined extinction responding patterns following heroin self-administration in glial fibrillary acidic protein thymidine kinase (GFAP-tk) transgenic mice, which have been previously demonstrated to show reduced formation of immature and mature neurons in the DG following treatment with ganciclovir (GCV). We found that extinction training increased DCX immunoreactivity in the dorsal DG as compared with animals undergoing forced abstinence, and that GCV-treated GFAP-tk mice displayed impaired extinction learning as compared to saline-treated mice. Our results suggest that extinction of drug-seeking behavior increases the formation of immature neurons in the DG and that these neurons may play a functional role in extinction learning.

  9. Fear Extinction as a Model for Synaptic Plasticity in Major Depressive Disorder

    PubMed Central

    Feige, Bernd; Blechert, Jens; Normann, Claus; Nissen, Christoph

    2014-01-01

    Background The neuroplasticity hypothesis of major depressive disorder proposes that a dysfunction of synaptic plasticity represents a basic pathomechanism of the disorder. Animal models of depression indicate enhanced plasticity in a ventral emotional network, comprising the amygdala. Here, we investigated fear extinction learning as a non-invasive probe for amygdala-dependent synaptic plasticity in patients with major depressive disorder and healthy controls. Methods Differential fear conditioning was measured in 37 inpatients with severe unipolar depression (International Classification of Diseases, 10th revision, criteria) and 40 healthy controls. The eye-blink startle response, a subcortical output signal that is modulated by local synaptic plasticity in the amygdala in fear acquisition and extinction learning, was recorded as the primary outcome parameter. Results After robust and similar fear acquisition in both groups, patients with major depressive disorder showed significantly enhanced fear extinction learning in comparison to healthy controls, as indicated by startle responses to conditioned stimuli. The strength of extinction learning was positively correlated with the total illness duration. Conclusions The finding of enhanced fear extinction learning in major depressive disorder is consistent with the concept that the disorder is characterized by enhanced synaptic plasticity in the amygdala and the ventral emotional network. Clinically, the observation emphasizes the potential of successful extinction learning, the basis of exposure therapy, in anxiety-related disorders despite the frequent comorbidity of major depressive disorder. PMID:25545818

  10. Classification of the fragrant styles and evaluation of the aromatic quality of flue-cured tobacco leaves by machine-learning methods.

    PubMed

    Gu, Li; Xue, Lichun; Song, Qi; Wang, Fengji; He, Huaqin; Zhang, Zhongyi

    2016-12-01

    During commercial transactions, the quality of flue-cured tobacco leaves must be characterized efficiently, and the evaluation system should be easily transferable across different traders. However, there are over 3000 chemical compounds in flue-cured tobacco leaves; thus, it is impossible to evaluate the quality of flue-cured tobacco leaves using all the chemical compounds. In this paper, we used Support Vector Machine (SVM) algorithm together with 22 chemical compounds selected by ReliefF-Particle Swarm Optimization (R-PSO) to classify the fragrant style of flue-cured tobacco leaves, where the Accuracy (ACC) and Matthews Correlation Coefficient (MCC) were 90.95% and 0.80, respectively. SVM algorithm combined with 19 chemical compounds selected by R-PSO achieved the best assessment performance of the aromatic quality of tobacco leaves, where the PCC and MSE were 0.594 and 0.263, respectively. Finally, we constructed two online tools to classify the fragrant style and evaluate the aromatic quality of flue-cured tobacco leaf samples. These tools can be accessed at http://bioinformatics.fafu.edu.cn/tobacco .

  11. Biostratigraphic case studies of six major extinctions

    NASA Technical Reports Server (NTRS)

    Sloan, R. E.

    1988-01-01

    Biostratigraphic case studies of six major extinctions show all are gradual save one, which is a catastrophic extinction of terrestrial origin. These extinctions show a continuum of environmental insults from major to minor. The major causes of these extinctions are positive and negative eustatic sea level changes, temperature, or ecological competition. Extraterrestrial causes should not be posited without positive association with a stratigraphically sharp extinction. The Cretaceous-Tertiary terrestrial extinction is considerably smaller in percentage of extinction than the marine extinction and is spread over 10 my of the Cretaceous and 1 my of the Tertiary. Sixty percent of the 30 dinosaurs in the northern Great Plains of the U.S. and Canada had become extinct in the 9 my before the late Maastrichtian sea level drop. The best data on the Permo-Triassic terrestrial extinction are from the Karoo basin of South Africa. This is a series of 6 extinctions in some 8 my, recorded in some 2800 meters of sediment. Precision of dating is enhanced by the high rate of accumulation of these sediments. Few data are readily available on the timing of the marine Permo-Triassic extinction, due to the very restricted number of sequences of Tatarian marine rocks. The terminal Ordovician extinction at 438 my is relatively rapid, taking place over about 0.5 my. The most significant aspect of this extinction is a eustatic sea level lowering associated with a major episode of glaciation. New data on this extinction is the reduction from 61 genera of trilobites in North America to 14, for a 77 percent extinction. Another Ordovician extinction present over 10 percent of the North American craton occurs at 454 my in the form of a catastrophic extinction due to a volcanic eruption which blanketed the U.S. east of the Transcontinental Arch. This is the only other sizeable extinction in the Ordovician.

  12. The extinction of the dinosaurs.

    PubMed

    Brusatte, Stephen L; Butler, Richard J; Barrett, Paul M; Carrano, Matthew T; Evans, David C; Lloyd, Graeme T; Mannion, Philip D; Norell, Mark A; Peppe, Daniel J; Upchurch, Paul; Williamson, Thomas E

    2015-05-01

    Non-avian dinosaurs went extinct 66 million years ago, geologically coincident with the impact of a large bolide (comet or asteroid) during an interval of massive volcanic eruptions and changes in temperature and sea level. There has long been fervent debate about how these events affected dinosaurs. We review a wealth of new data accumulated over the past two decades, provide updated and novel analyses of long-term dinosaur diversity trends during the latest Cretaceous, and discuss an emerging consensus on the extinction's tempo and causes. Little support exists for a global, long-term decline across non-avian dinosaur diversity prior to their extinction at the end of the Cretaceous. However, restructuring of latest Cretaceous dinosaur faunas in North America led to reduced diversity of large-bodied herbivores, perhaps making communities more susceptible to cascading extinctions. The abruptness of the dinosaur extinction suggests a key role for the bolide impact, although the coarseness of the fossil record makes testing the effects of Deccan volcanism difficult.

  13. Flood basalts and extinction events

    NASA Technical Reports Server (NTRS)

    Stothers, Richard B.

    1993-01-01

    The largest known effusive eruptions during the Cenozoic and Mesozoic Eras, the voluminous flood basalts, have long been suspected as being associated with major extinctions of biotic species. Despite the possible errors attached to the dates in both time series of events, the significance level of the suspected correlation is found here to be 1 percent to 4 percent. Statistically, extinctions lag eruptions by a mean time interval that is indistinguishable from zero, being much less than the average residual derived from the correlation analysis. Oceanic flood basalts, however, must have had a different biological impact, which is still uncertain owing to the small number of known examples and differing physical factors. Although not all continental flood basalts can have produced major extinction events, the noncorrelating eruptions may have led to smaller marine extinction events that terminated at least some of the less catastrophically ending geologic stages. Consequently, the 26 Myr quasi-periodicity seen in major marine extinctions may be only a sampling effect, rather than a manifestation of underlying periodicity.

  14. Flood basalts and mass extinctions

    NASA Technical Reports Server (NTRS)

    Morgan, W. Jason

    1988-01-01

    There appears to be a correlation between the times of flood basalts and mass-extinction events. There is a correlation of flood basalts and hotspot tracks--flood basalts appear to mark the beginning of a new hotspot. Perhaps there is an initial instability in the mantle that bursts forth as a flood basalt but then becomes a steady trickle that persists for many tens of millions of years. Suppose that flood basalts and not impacts cause the environmental changes that lead to mass-extinctions. This is a very testable hypothesis: it predicts that the ages of the flows should agree exactly with the times of extinctions. The Deccan and K-T ages agree with this hypothesis; An iridium anomaly at extinction boundaries apparently can be explained by a scaled-up eruption of the Hawaiian type; the occurrence of shocked-quartz is more of a problem. However if the flood basalts are all well dated and their ages indeed agree with extinction times, then surely some mechanism to appropriately produce shocked-quartz will be found.

  15. Flood basalts and extinction events

    NASA Technical Reports Server (NTRS)

    Stothers, Richard B.

    1993-01-01

    The largest known effusive eruptions during the Cenozoic and Mesozoic Eras, the voluminous flood basalts, have long been suspected as being associated with major extinctions of biotic species. Despite the possible errors attached to the dates in both time series of events, the significance level of the suspected correlation is found here to be 1 percent to 4 percent. Statistically, extinctions lag eruptions by a mean time interval that is indistinguishable from zero, being much less than the average residual derived from the correlation analysis. Oceanic flood basalts, however, must have had a different biological impact, which is still uncertain owing to the small number of known examples and differing physical factors. Although not all continental flood basalts can have produced major extinction events, the noncorrelating eruptions may have led to smaller marine extinction events that terminated at least some of the less catastrophically ending geologic stages. Consequently, the 26 Myr quasi-periodicity seen in major marine extinctions may be only a sampling effect, rather than a manifestation of underlying periodicity.

  16. Extinction circuits for fear and addiction overlap in prefrontal cortex

    PubMed Central

    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 critical for the extinction of both fear and drug-seeking behaviors. Moreover, a dorsal-ventral distinction is apparent within the mPFC, such that the prelimbic (PL-mPFC) cortex drives the expression of fear and drug seeking, whereas the infralimbic (IL-mPFC) cortex suppresses these behaviors after extinction. For conditioned fear, the dorsal-ventral dichotomy is accomplished via divergent projections to different subregions of the amygdala, whereas for drug seeking, it is accomplished via divergent projections to the subregions of the nucleus accumbens. Given that the mPFC represents a common node in the extinction circuit for these behaviors, treatments that target this region may help alleviate symptoms of both anxiety and addictive disorders by enhancing extinction memory. PMID:19380710

  17. A hippocampal Cdk5 pathway regulates extinction of contextual fear

    PubMed Central

    Sananbenesi, Farahnaz; Fischer, Andre; Wang, Xinyu; Schrick, Christina; Neve, Rachael; Radulovic, Jelena; Tsai, Li-Huei

    2008-01-01

    Treatment of emotional disorders involves the promotion of extinction processes, which are defined as the learned reduction of fear. The molecular mechanisms underlying extinction have only begun to be elucidated. By employing genetic and pharmacological approaches in mice, we show here that extinction requires downregulation of Rac-1 and cyclin-dependent kinase 5 (Cdk5), and upregulation of p21 activated kinase-1 (PAK-1) activity. This is physiologically achieved by a Rac-1–dependent relocation of the Cdk5 activator p35 from the membrane to the cytosol and dissociation of p35 from PAK-1. Moreover, our data suggest that Cdk5/p35 activity prevents extinction in part by inhibition of PAK-1 activity in a Rac-1–dependent manner. We propose that extinction of contextual fear is regulated by counteracting components of a molecular pathway involving Rac-1, Cdk5 and PAK-1. Our data suggest that this pathway could provide a suitable target for therapeutic treatment of emotional disorders. PMID:17632506

  18. Effects of endocannabinoid and endovanilloid systems on aversive memory extinction.

    PubMed

    Laricchiuta, Daniela; Centonze, Diego; Petrosini, Laura

    2013-11-01

    In contextual fear conditioning animals have to integrate various elemental stimuli into a coherent representation of the condition and then associate context representation with punishment. Although several studies indicated the modulating role of endocannabinoid system (ECS) on the associative learning, ECS effect on contextual fear conditioning requires further investigations. The present study assessed the effects of the increased endocannabinoid anandamide (AEA) tone on acquisition, retrieval and extinction of the contextual fear conditioning. Given that AEA may bind to cannabinoid type 1 (CB1) receptors as well as to postsynaptic ionotropic Transient Receptor Potential Vanilloid type 1 (TRPV1) channels, particular attention was paid in determining how the increased AEA tone influenced fear responses. Furthermore, it was investigated how the ECS modulated the effects of stress-sensitization on fear response. Thus, mice submitted or not to a social defeat stress protocol were treated with drugs acting on ECS, CB1 receptors or TRPV1 channels and tested in a contextual fear conditioning whose conditioning, retrieval and extinction phases were analyzed. ECS activation influenced the extinction process and contrasted the stress effects on fear memory. Furthermore, CB1 receptor antagonist blocked and TRPV1 channel antagonist promoted short- and long-term extinction. The present study indicates that ECS controls the extinction of aversive memories in the contextual fear conditioning.

  19. Fear conditioning and extinction in pediatric obsessive-compulsive disorder.

    PubMed

    Geller, Daniel A; McGuire, Joseph F; Orr, Scott P; Pine, Daniel S; Britton, Jennifer C; Small, Brent J; Murphy, Tanya K; Wilhelm, Sabine; Storch, Eric A

    2017-02-01

    Fear acquisition and extinction are central constructs in the cognitive-behavioral model of obsessive-compulsive disorder (OCD), which underlies exposure-based cognitive-behavioral therapy. Youths with OCD may have impairments in fear acquisition and extinction that carry treatment implications. Eighty youths (39 OCD, 41 healthy controls [HC]) completed clinical interviews, rating scales, and a differential conditioning task that included habituation, acquisition, and extinction phases. Skin conductance response (SCR) served as the primary dependent measure. During habituation, participants with OCD exhibited a stronger orienting SCR to initial stimuli relative to HC participants. During acquisition, differential fear conditioning was observed for both groups as evidenced by larger SCRs to the visual conditioned stimulus paired with an aversive unconditioned stimulus (CS+) compared with a CS-; OCD participants exhibited a larger SCR to the CS+ relative to HC participants. The absolute magnitude of the unconditioned fear response was significantly larger in participants with OCD, compared with HC participants. During extinction, OCD participants continued to exhibit a differential SCR to the CS+ and CS-, whereas HC participants exhibited diminished SCR to both stimuli. Participants with OCD exhibit a different pattern of fear extinction relative to HC participants, suggestive of greater fear acquisition and impaired inhibitory learning.

  20. Extinction revisited: similarities between extinction and reductions in US intensity in classical conditioning of the rabbit's nictitating membrane response.

    PubMed

    Kehoe, E James; White, Natasha E

    2002-05-01

    The mechanisms of extinction were examined by reducing the intensity of the unconditioned stimulus (US) after acquisition training to determine whether such reductions lie on a continuum with CS-alone extinction. The experiments revealed that reductions in US intensity yielded extinction-like effects. Specifically, there were proportional reductions in the daily mean level of responding across sessions. There were also persistent within-session declines and between-session increases of responding analogous to spontaneous recovery. Surprisingly, even when US intensity was held constant, within-session declines and between-session increases were apparent. The results are discussed with respect to possible contributions from unlearning, new learning, generalization decrement, and nonassociative loss, especially CS-specific attentional changes and CR-specific reactive inhibition.

  1. Different mechanisms of fear extinction dependent on length of time since fear acquisition

    PubMed Central

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

    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 unsignaled presentations of the unconditioned stimulus (reinstatement). However, there also is evidence to suggest that extinction is an “unlearning” process corresponding to depotentiation of potentiated synapses within the amygdala. Because depotentiation is induced more readily at short intervals following LTP induction and is not inducible at all at a sufficient delay, it may be that extinction initiated shortly following fear acquisition preferentially engages depotentiation/“unlearning,” whereas extinction initiated at longer delays recruits a different mechanism. We investigated this possibility through a series of behavioral experiments examining the recoverability of conditioned fear following extinction. Consistent with an inhibitory learning mechanism of extinction, rats extinguished 24–72 h following acquisition exhibited moderate to strong reinstatement, renewal, and spontaneous recovery. In contrast, and consistent with an erasure mechanism, rats extinguished 10 min to 1 h after acquisition exhibited little or no reinstatement, renewal, or spontaneous recovery. These data support a model in which different neural mechanisms are recruited depending on the temporal delay of fear extinction. PMID:16585797

  2. A hippocampal insulin-growth factor 2 pathway regulates the extinction of fear memories

    PubMed Central

    Agis-Balboa, Roberto Carlos; Arcos-Diaz, Dario; Wittnam, Jessica; Govindarajan, Nambirajan; Blom, Kim; Burkhardt, Susanne; Haladyniak, Ulla; Agbemenyah, Hope Yao; Zovoilis, Athanasios; Salinas-Riester, Gabriella; Opitz, Lennart; Sananbenesi, Farahnaz; Fischer, Andre

    2011-01-01

    Extinction learning refers to the phenomenon that a previously learned response to an environmental stimulus, for example, the expression of an aversive behaviour upon exposure to a specific context, is reduced when the stimulus is repeatedly presented in the absence of a previously paired aversive event. Extinction of fear memories has been implicated with the treatment of anxiety disease but the molecular processes that underlie fear extinction are only beginning to emerge. Here, we show that fear extinction initiates upregulation of hippocampal insulin-growth factor 2 (Igf2) and downregulation of insulin-growth factor binding protein 7 (Igfbp7). In line with this observation, we demonstrate that IGF2 facilitates fear extinction, while IGFBP7 impairs fear extinction in an IGF2-dependent manner. Furthermore, we identify one cellular substrate of altered IGF2 signalling during fear extinction. To this end, we show that fear extinction-induced IGF2/IGFBP7 signalling promotes the survival of 17–19-day-old newborn hippocampal neurons. In conclusion, our data suggest that therapeutic strategies that enhance IGF2 signalling and adult neurogenesis might be suitable to treat disease linked to excessive fear memory. PMID:21873981

  3. Enhancing and impairing extinction of habit memory through modulation of NMDA receptors in the dorsolateral striatum.

    PubMed

    Goodman, Jarid; Ressler, Reed L; Packard, Mark G

    2017-04-02

    The present experiments investigated the involvement of N-methyl-d-aspartate (NMDA) receptors of the dorsolateral striatum (DLS) in consolidation of extinction in a habit memory task. Adult male Long-Evans rats were initially trained in a food-reinforced response learning version of a plus-maze task and were subsequently given extinction training in which the food was removed from the maze. In experiment 1, immediately after the first day of extinction training, rats received bilateral intra-DLS injections of the NMDA receptor antagonist 2-amino-5-phosphonopentanoic acid (AP5; 2µg/side) or physiological saline. In experiment 2, immediately following the first day of extinction training, animals were given intra-DLS injections of NMDA receptor partial agonist d-cycloserine (DCS; 10 or 20µg/side) or saline. In both experiments, the number of perseverative trials (a trial in which a rat made the same previously reinforced body-turn response) and latency to reach the previously correct food well were used as measures of extinction behavior. Results indicated that post-training intra-DLS injections of AP5 impaired extinction. In contrast, post-training intra-DLS infusions of DCS (20µg) enhanced extinction. Intra-DLS administration of AP5 or DCS given two hours after extinction training did not influence extinction of response learning, indicating that immediate post-training administration of AP5 and DCS specifically influenced consolidation of the extinction memory. The present results indicate a critical role for DLS NMDA receptors in modulating extinction of habit memory and may be relevant to developing therapeutic approaches to combat the maladaptive habits observed in human psychopathologies in which DLS-dependent memory has been implicated (e.g. drug addiction and relapse and obsessive compulsive disorder).

  4. Enhancing dopaminergic signaling and histone acetylation promotes long-term rescue of deficient fear extinction

    PubMed Central

    Whittle, N; Maurer, V; Murphy, C; Rainer, J; Bindreither, D; Hauschild, M; Scharinger, A; Oberhauser, M; Keil, T; Brehm, C; Valovka, T; Striessnig, J; Singewald, N

    2016-01-01

    Extinction-based exposure therapy is used to treat anxiety- and trauma-related disorders; however, there is the need to improve its limited efficacy in individuals with impaired fear extinction learning and to promote greater protection against return-of-fear phenomena. Here, using 129S1/SvImJ mice, which display impaired fear extinction acquisition and extinction consolidation, we revealed that persistent and context-independent rescue of deficient fear extinction in these mice was associated with enhanced expression of dopamine-related genes, such as dopamine D1 (Drd1a) and -D2 (Drd2) receptor genes in the medial prefrontal cortex (mPFC) and amygdala, but not hippocampus. Moreover, enhanced histone acetylation was observed in the promoter