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Sample records for learning leave extinction

  1. Genetic disruptions of Drosophila Pavlovian learning leave extinction learning intact

    PubMed Central

    Qin, Hongtao; Dubnau, Josh

    2009-01-01

    Individuals that experience traumatic events may develop persistent post-traumatic stress disorder (PTSD). Patients with this disorder are commonly treated with exposure therapy, which has had limited long-term success. In experimental neurobiology, fear extinction is a model for exposure therapy. In this behavioral paradigm, animals are repeatedly exposed in a safe environment to the fearful stimulus, which leads to greatly reduced fear. Studying animal models of extinction already has lead to better therapeutic strategies and development of new candidate drugs. Lack of a powerful genetic model of extinction, however, has limited progress in identifying underlying molecular and genetic factors. In this study, we established a robust behavioral paradigm to study the short term effect (acquisition) of extinction in Drosophila melanogaster. We focused on the extinction of olfactory aversive one-day memory with a task that has been the main workhorse for genetics of memory in flies. Using this paradigm, we demonstrate that extinction can inhibit each of two genetically distinct forms of consolidated memory. We then used a series of single-gene mutants with known impact on associative learning, to examine effects on extinction. We find that extinction is intact in each of these mutants, suggesting that extinction learning relies on different molecular mechanisms than does Pavlovian learning. PMID:20015341

  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. 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. PMID:25452113

  5. Neural mechanisms of extinction learning and retrieval.

    PubMed

    Quirk, Gregory J; Mueller, Devin

    2008-01-01

    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.

  6. 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

  7. 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.

  8. Neural signals of vicarious extinction learning.

    PubMed

    Golkar, Armita; Haaker, Jan; Selbing, Ida; Olsson, Andreas

    2016-10-01

    Social transmission of both threat and safety is ubiquitous, but little is known about the neural circuitry underlying vicarious safety learning. This is surprising given that these processes are critical to flexibly adapt to a changeable environment. To address how the expression of previously learned fears can be modified by the transmission of social information, two conditioned stimuli (CS + s) were paired with shock and the third was not. During extinction, we held constant the amount of direct, non-reinforced, exposure to the CSs (i.e. direct extinction), and critically varied whether another individual-acting as a demonstrator-experienced safety (CS + vic safety) or aversive reinforcement (CS + vic reinf). During extinction, ventromedial prefrontal cortex (vmPFC) responses to the CS + vic reinf increased but decreased to the CS + vic safety This pattern of vmPFC activity was reversed during a subsequent fear reinstatement test, suggesting a temporal shift in the involvement of the vmPFC. Moreover, only the CS + vic reinf association recovered. Our data suggest that vicarious extinction prevents the return of conditioned fear responses, and that this efficacy is reflected by diminished vmPFC involvement during extinction learning. The present findings may have important implications for understanding how social information influences the persistence of fear memories in individuals suffering from emotional disorders. PMID:27278792

  9. Neural signals of vicarious extinction learning.

    PubMed

    Golkar, Armita; Haaker, Jan; Selbing, Ida; Olsson, Andreas

    2016-10-01

    Social transmission of both threat and safety is ubiquitous, but little is known about the neural circuitry underlying vicarious safety learning. This is surprising given that these processes are critical to flexibly adapt to a changeable environment. To address how the expression of previously learned fears can be modified by the transmission of social information, two conditioned stimuli (CS + s) were paired with shock and the third was not. During extinction, we held constant the amount of direct, non-reinforced, exposure to the CSs (i.e. direct extinction), and critically varied whether another individual-acting as a demonstrator-experienced safety (CS + vic safety) or aversive reinforcement (CS + vic reinf). During extinction, ventromedial prefrontal cortex (vmPFC) responses to the CS + vic reinf increased but decreased to the CS + vic safety This pattern of vmPFC activity was reversed during a subsequent fear reinstatement test, suggesting a temporal shift in the involvement of the vmPFC. Moreover, only the CS + vic reinf association recovered. Our data suggest that vicarious extinction prevents the return of conditioned fear responses, and that this efficacy is reflected by diminished vmPFC involvement during extinction learning. The present findings may have important implications for understanding how social information influences the persistence of fear memories in individuals suffering from emotional disorders.

  10. D-cycloserine facilitates context-specific fear extinction learning.

    PubMed

    Bouton, Mark E; Vurbic, Drina; Woods, Amanda M

    2008-10-01

    D-cycloserine (DCS) may facilitate fear extinction learning, but the behavioral consequences and mechanisms behind this effect are not well understood at present. In this paper, we re-analyze data from previously reported null result experiments and find that rats showing above-median extinction learning during DCS treatment benefited from the drug, whereas rats showing below-median (and in this case little) extinction learning did not. Two additional experiments found that DCS facilitated extinction learning when specifically combined with a moderate, but not a small, number of extinction trials. DCS thus facilitates extinction learning only if the behavioral procedure first engages the extinction learning process. The benefits of the drug, however, were specific to the context in which extinction was learned--i.e., DCS did not prevent or influence the renewal of fear observed when the extinguished cue was tested in the original conditioning context.

  11. 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

  12. 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.

  13. 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

  14. Hippocampus NMDA receptors selectively mediate latent extinction of place learning.

    PubMed

    Goodman, Jarid; Gabriele, Amanda; Packard, Mark G

    2016-09-01

    Extinction of maze learning may be achieved with or without the animal performing the previously acquired response. In typical "response extinction," animals are given the opportunity to make the previously acquired approach response toward the goal location of the maze without reinforcement. In "latent extinction," animals are not given the opportunity to make the previously acquired response and instead are confined to the previous goal location without reinforcement. Previous evidence indicates that the effectiveness of these protocols may depend on the type of memory being extinguished. Thus, one aim of the present study was to further examine the effectiveness of response and latent extinction protocols across dorsolateral striatum (DLS)-dependent response learning and hippocampus-dependent place learning tasks. In addition, previous neural inactivation experiments indicate a selective role for the hippocampus in latent extinction, but have not investigated the precise neurotransmitter mechanisms involved. Thus, the present study also examined whether latent extinction of place learning might depend on NMDA receptor activity in the hippocampus. In experiment 1, adult male Long-Evans rats were trained in a response learning task in a water plus-maze, in which animals were reinforced to make a consistent body-turn response to reach an invisible escape platform. Results indicated that response extinction, but not latent extinction, was effective at extinguishing memory in the response learning task. In experiment 2, rats were trained in a place learning task, in which animals were reinforced to approach a consistent spatial location containing the hidden escape platform. In experiment 2, animals also received intra-hippocampal infusions of the NMDA receptor antagonist 2-amino-5-phosphopentanoic acid (AP5; 5.0 or 7.5 ug/0.5 µg) or saline vehicle immediately before response or latent extinction training. Results indicated that both extinction protocols were

  15. Hippocampus NMDA receptors selectively mediate latent extinction of place learning.

    PubMed

    Goodman, Jarid; Gabriele, Amanda; Packard, Mark G

    2016-09-01

    Extinction of maze learning may be achieved with or without the animal performing the previously acquired response. In typical "response extinction," animals are given the opportunity to make the previously acquired approach response toward the goal location of the maze without reinforcement. In "latent extinction," animals are not given the opportunity to make the previously acquired response and instead are confined to the previous goal location without reinforcement. Previous evidence indicates that the effectiveness of these protocols may depend on the type of memory being extinguished. Thus, one aim of the present study was to further examine the effectiveness of response and latent extinction protocols across dorsolateral striatum (DLS)-dependent response learning and hippocampus-dependent place learning tasks. In addition, previous neural inactivation experiments indicate a selective role for the hippocampus in latent extinction, but have not investigated the precise neurotransmitter mechanisms involved. Thus, the present study also examined whether latent extinction of place learning might depend on NMDA receptor activity in the hippocampus. In experiment 1, adult male Long-Evans rats were trained in a response learning task in a water plus-maze, in which animals were reinforced to make a consistent body-turn response to reach an invisible escape platform. Results indicated that response extinction, but not latent extinction, was effective at extinguishing memory in the response learning task. In experiment 2, rats were trained in a place learning task, in which animals were reinforced to approach a consistent spatial location containing the hidden escape platform. In experiment 2, animals also received intra-hippocampal infusions of the NMDA receptor antagonist 2-amino-5-phosphopentanoic acid (AP5; 5.0 or 7.5 ug/0.5 µg) or saline vehicle immediately before response or latent extinction training. Results indicated that both extinction protocols were

  16. 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.

  17. Noradrenergic modulation of extinction learning and exposure therapy.

    PubMed

    Mueller, Devin; Cahill, Shawn P

    2010-03-17

    Memory consolidation is enhanced by emotional arousal, an effect mediated by noradrenergic beta-receptor signaling. Norepinephrine strengthens consolidation of both appetitive and aversive learning, and is implicated in extinction of conditioned responses. In this review, we summarize work on the noradrenergic mechanisms of extinction learning and implications for extinction-based exposure therapy. The evidence suggests that norepinephrine release evoked by conditioned stimuli during extinction strengthens extinction memory via beta-receptor signaling. The modulatory effect of norepinephrine during extinction depends on predictable presentation of conditioned stimuli and optimal levels of norepinephrine release. Mechanistically, norepinephrine acts to increase cellular excitability and enhance synaptic plasticity within extinction-related neural circuitry. Currently, drugs that modulate norepinephrine are being used to treat symptoms of anxiety disorders, and are now being tested as pharmacotherapeutic prophalactics in the prevention of chronic posttraumatic stress reactions and as adjuncts to extinction-based exposure therapy. Studies of these new applications of noradrenergic drugs show a converging pattern of results with basic science suggesting ways in which basic laboratory findings can be translated into procedures to enhance clinical outcomes.

  18. 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.

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

    PubMed

    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

  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. The impact of context relevance during extinction learning.

    PubMed

    Lucke, Sara; Lachnit, Harald; Stüttgen, Maik C; Uengoer, Metin

    2014-09-01

    In two predictive-learning experiments, we investigated the role of the informational value of contexts for the formation of context-specific extinction learning. The contexts were each composed of two elements from two dimensions, A and B. In Phase 1 of each experiment, participants received acquisition training with a target cue Z in context A1B1 (the numbers assign particular values on the context dimensions). In Phase 2, participants were trained with conditional discriminations between two other cues, X and Y, for which only one of the two context dimensions was relevant. In a third phase, participants received extinction trials with cue Z in context A2B2. During a final test phase, we observed that a partial change of the extinction context disrupted extinction performance when the extinction context was changed on the dimension that had been trained as being relevant for the conditional discrimination. However, when the extinction context was changed on the irrelevant context dimension, extinction performance was not affected. Our results are consistent with the idea that relevant contexts receive more attention than do irrelevant contexts, leading to stronger context-specific processing of information learned in the former than in the latter type of contexts. PMID:24934214

  2. The impact of context relevance during extinction learning.

    PubMed

    Lucke, Sara; Lachnit, Harald; Stüttgen, Maik C; Uengoer, Metin

    2014-09-01

    In two predictive-learning experiments, we investigated the role of the informational value of contexts for the formation of context-specific extinction learning. The contexts were each composed of two elements from two dimensions, A and B. In Phase 1 of each experiment, participants received acquisition training with a target cue Z in context A1B1 (the numbers assign particular values on the context dimensions). In Phase 2, participants were trained with conditional discriminations between two other cues, X and Y, for which only one of the two context dimensions was relevant. In a third phase, participants received extinction trials with cue Z in context A2B2. During a final test phase, we observed that a partial change of the extinction context disrupted extinction performance when the extinction context was changed on the dimension that had been trained as being relevant for the conditional discrimination. However, when the extinction context was changed on the irrelevant context dimension, extinction performance was not affected. Our results are consistent with the idea that relevant contexts receive more attention than do irrelevant contexts, leading to stronger context-specific processing of information learned in the former than in the latter type of contexts.

  3. Multiple sites of extinction for a single learned response

    PubMed Central

    Mauk, Michael D.

    2012-01-01

    Most learned responses can be diminished by extinction, a process that can be engaged when a conditioned stimulus (CS) is presented but not reinforced. We present evidence that plasticity in at least two brain regions can mediate extinction of responses produced by trace eyelid conditioning, where the CS and the reinforcing stimulus are separated by a stimulus-free interval. We observed individual differences in the effects of blocking extinction mechanisms in the cerebellum, the structure that, along with several forebrain structures, mediates acquisition of trace eyelid responses; in some rabbits extinction was prevented, whereas in others it was largely unaffected. We also show that cerebellar mechanisms can mediate extinction when noncerebellar mechanisms are bypassed. Together, these observations indicate that trace eyelid responses can be extinguished via processes operating at more than one site, one in the cerebellum and one upstream in forebrain. The relative contributions of these sites may vary from animal to animal and situation to situation. PMID:21940608

  4. Behavioral and neural bases of extinction learning in Hermissenda.

    PubMed

    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

  5. 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

  6. Increased prefrontal cortex neurogranin enhances plasticity and extinction learning.

    PubMed

    Zhong, Ling; Brown, Joshua; Kramer, Audra; Kaleka, Kanwardeep; Petersen, Amber; Krueger, Jamie N; Florence, Matthew; Muelbl, Matthew J; Battle, Michelle; Murphy, Geoffrey G; Olsen, Christopher M; Gerges, Nashaat Z

    2015-05-13

    Increasing plasticity in neurons of the prefrontal cortex (PFC) has been proposed as a possible therapeutic tool to enhance extinction, a process that is impaired in post-traumatic stress disorder, schizophrenia, and addiction. To test this hypothesis, we generated transgenic mice that overexpress neurogranin (a calmodulin-binding protein that facilitates long-term potentiation) in the PFC. Neurogranin overexpression in the PFC enhanced long-term potentiation and increased the rates of extinction learning of both fear conditioning and sucrose self-administration. Our results indicate that elevated neurogranin function within the PFC can enhance local plasticity and increase the rate of extinction learning across different behavioral tasks. Thus, neurogranin can provide a molecular link between enhanced plasticity and enhanced extinction.

  7. Reward-produced memories regulate memory-discrimination learning, extinction, and other forms of discrimination learning.

    PubMed

    Capaldi, E J; Birmingham, K M

    1998-07-01

    In memory-discrimination learning, reward-produced memories are differentially rewarded such that they are the only stimuli available to support discriminative responding. Memory-discrimination learning was used in this study as follows: Reward-produced memories that were assumed to regulate instrumental performance in previously reported extinction and discrimination learning investigations were isolated and explicitly differentially reinforced (prior to a shift to extinction) in each of 4 runway investigations with rats. Results obtained here in the explicit discrimination learning stage and in the subsequent extinction stage were consistent with the prediction of the memory view and with prior discrimination learning and extinction findings. The memory interpretation was applied to memory-discrimination learning, to extinction, and to 2 other types of discrimination learning. It appears that a theory must use reward-produced memories to explain all 4 types of discrimination learning.

  8. Learning to inhibit the response during instrumental (operant) extinction.

    PubMed

    Bouton, Mark E; Trask, Sydney; Carranza-Jasso, Rodrigo

    2016-07-01

    Five experiments tested implications of the idea that instrumental (operant) extinction involves learning to inhibit the learned response. All experiments used a discriminated operant procedure in which rats were reinforced for lever pressing or chain pulling in the presence of a discriminative stimulus (S), but not in its absence. In Experiment 1, extinction of the response (R) in the presence of S weakened responding in S, but equivalent nonreinforced exposure to S (without the opportunity to make R) did not. Experiment 2 replicated that result and found that extinction of R had no effect on a different R that had also been reinforced in the stimulus. In Experiments 3 and 4, rats first learned to perform several different stimulus and response combinations (S1R1, S2R1, S3R2, and S4R2). Extinction of a response in one stimulus (i.e., S1R1) transferred and weakened the same response, but not a different response, when it was tested in another stimulus (i.e., S2R1 but not S3R2). In Experiment 5, extinction still transferred between S1 and S2 when the stimuli set the occasion for R's association with different types of food pellets. The results confirm the importance of response inhibition in instrumental extinction: Nonreinforcement of the response in S causes the most effective suppression of responding, and response suppression is specific to the response but transfers and influences performance of the same response when it is occasioned by other stimuli. Theoretical and practical implications are discussed. (PsycINFO Database Record PMID:27379715

  9. 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…

  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. 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…

  14. 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

  15. 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.

  16. 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.

  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. 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

  19. 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.

  20. 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. PMID:1129357

  1. Transient inactivation of the pigeon hippocampus or the nidopallium caudolaterale during extinction learning impairs extinction retrieval in an appetitive conditioning paradigm.

    PubMed

    Lengersdorf, Daniel; Stüttgen, Maik C; Uengoer, Metin; Güntürkün, Onur

    2014-05-15

    The majority of experiments exploring context-dependent extinction learning employ Pavlovian fear conditioning in rodents. Since mechanisms of appetitive and aversive learning are known to differ at the neuronal level, we sought to investigate extinction learning in an appetitive setting. Working with pigeons, we established a within-subject ABA renewal paradigm based on Rescorla (Q J Exp Psychol 61:1793) and combined it with pharmacological interventions during extinction. From the fear conditioning literature, it is known that both prefrontal cortex and the hippocampus are core structures for context-specific extinction learning. Accordingly, we transiently inactivated the nidopallium caudolaterale (NCL, a functional analogue of mammalian prefrontal cortex) and the hippocampus in separate experiments by intracranial infusion of the sodium-channel blocker tetrodotoxin immediately before extinction training. We find that TTX in both structures non-specifically suppresses conditioned responding, as revealed by a reduction of response rate to both the extinguished conditioned stimulus and a control stimulus which remained reinforced throughout the experiment. Furthermore, TTX during extinction training impaired later extinction retrieval assessed under drug-free conditions. This was true when responding to the extinguished stimulus was assessed in the context of extinction but not when tested in the context of acquisition, although both contexts were matched with respect to their history of conditioning. These results indicate that both NCL and hippocampus are involved in extinction learning under appetitive conditions or, more specifically, in the consolidation of extinction memory, and that their contribution to extinction is context-specific.

  2. 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…

  3. A role of protein degradation in memory consolidation after initial learning and extinction learning in the honeybee (Apis mellifera).

    PubMed

    Felsenberg, Johannes; Dombrowski, Vincent; Eisenhardt, Dorothea

    2012-09-17

    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 applied after initial learning. This result supports the idea that MG132 targets an ongoing consolidation process. Furthermore, we demonstrate that the sensitivity of memory formation after initial learning and extinction learning to MG132 depends in the same way on the number of CS-US trials and the intertrial interval applied during initial learning. This supports the idea that the learning parameters during acquisition are critical for memory formation after extinction and that protein degradation in both learning processes might be functionally linked.

  4. 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.

  5. Extinction as new learning versus unlearning: considerations from a computer simulation of the cerebellum.

    PubMed

    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 extinction and savings in eyelid conditioning, with predictions born out by experiments. We review previous work showing that the simulation reproduces behavioral phenomena and lesion effects generally taken as evidence that extinction does not reverse acquisition, even though its plasticity is bidirectional with no site dedicated to inhibitory learning per se. In contrast, we show that even though the sites of plasticity are, in general, affected in opposite directions by acquisition and extinction training, most synapses do not return to their naive state after acquisition followed by extinction. These results suggest caution in interpreting a range of observations as necessarily supporting extinction as unlearning or extinction as new inhibitory learning. We argue that the question "is extinction reversal of acquisition or new inhibitory learning?" is therefore not well posed because the answer may depend on factors such as the brain system in question or the level of analysis considered.

  6. 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. PMID:23945999

  7. 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…

  8. 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…

  9. 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…

  10. 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…

  11. 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…

  12. A Dynamic Theory of Acquisition and Extinction in Operant Learning.

    PubMed

    Dragoi, Valentin

    1997-03-01

    This article offers a new neural network framework for understanding both the transients and the asymptotes of operant (instrumental) learning. The theory shows that interplay between simple short and long-term memory mechanisms is sufficient to explain a large number of operant phenomena. It describes short- and long-term effects of reinforcement and how these effects modulate the operant response, how novel events are detected and processed, and how their consequences also modulate the operant response. The critical features of the present theory are: (1) reinforcement expectancy is defined as the aggregate prediction of response-reinforcement and stimulus-reinforcement associations; (2) reinforcement expectancy controls the rate of increase of the operant response; (3) the response is controlled by a behavioral inhibition unit which integrates the mismatch between expected (long-term) and experienced (short-term) events. The model predicts the general features of several operant phenomena such as response selection, development of preference under different manipulations of reinforcement probabilities, negative contrast, partial reinforcement extinction effect, and spontaneous recovery. Implications of the present theory for other operant conditioning phenomena, classical conditioning, and avoidance behavior are suggested. Copyright 1997 Elsevier Science Ltd. All Rights Reserved.

  13. 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. PMID:26472643

  14. 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.

  15. Learning and memory in conditioned fear extinction: effects of D-cycloserine.

    PubMed

    Vervliet, Bram

    2008-03-01

    This review addresses the effects of the cognitive enhancer D-cycloserine (DCS) on the memory processes that occur in conditioned fear extinction, which is the experimental model for exposure techniques to reduce clinical anxiety. All reported rat studies show an enhanced fear extinction effect when DCS is administered acutely before or shortly after extinction training. DCS also promotes the generalization of this fear extinction effect. In addition, DCS reduces some forms of relapse (reduced reinstatement, reduced spontaneous recovery), but not others (contextual renewal, rapid reacquisition). It is argued that this pattern of results is best explained by assuming that DCS promotes extinction learning to the background context, resulting in enhanced contextual inhibition. Four human studies have produced mixed results, but some methodological issues complicate the reported failures. It is concluded that DCS is a promising tool as an adjunct to extinction techniques in exposure treatment, but that more pre-clinical and clinical research is needed to fully characterize its behavioral consequences.

  16. 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

  17. 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. PMID:27262427

  18. 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.

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

    PubMed Central

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

    2015-01-01

    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 (0.4 g/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. PMID:26234587

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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.

  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. Sensory Cortical Population Dynamics Uniquely Track Behavior across Learning and Extinction

    PubMed Central

    Katz, Donald B.

    2014-01-01

    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. PMID:24453316

  7. 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

  8. Rethinking Extinction.

    PubMed

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

    2015-10-01

    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

  9. 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

  10. Rethinking Extinction.

    PubMed

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

    2015-10-01

    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.

  11. 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

  12. 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

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

    PubMed

    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

  14. 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

  15. D-cycloserine deters reacquisition of cocaine self-administration by augmenting extinction learning.

    PubMed

    Nic Dhonnchadha, Bríd A; 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.

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

    PubMed

    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

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

    PubMed

    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.

  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. PMID:25716297

  20. Discrimination learning and extinction in paramecia (P. caudatum).

    PubMed

    Armus, Harvard L; Montgomery, Amber R; Gurney, Rebecca L

    2006-06-01

    Prior attempts to condition a one-celled organism, paramecium, by either classical or instrumental procedures have yielded both positive and negative results. As the results of those studies may be subject to several interpretations other than one indicating learning, it was decided to use a more traditional technique for the present study. This experiment was designed to assess whether aversive electric shock could be used to train paramecia on a brightness discrimination task, a procedure that has been used in animal learning research. The results indicated that such learning may have occurred.

  1. 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.

  2. 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.

  3. 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.

  4. Differential contributions of infralimbic prefrontal cortex and nucleus accumbens during reward-based learning and extinction.

    PubMed

    Francois, Jennifer; Huxter, John; Conway, Michael W; Lowry, John P; Tricklebank, Mark D; Gilmour, Gary

    2014-01-01

    Using environmental cues for the prediction of future events is essential for survival. Such cue-outcome associations are thought to depend on mesolimbic circuitry involving the nucleus accumbens (NAc) and prefrontal cortex (PFC). Several studies have identified roles for both NAc and PFC in the expression of stable goal-directed behaviors, but much remains unknown about their roles during learning of such behaviors. To further address this question, we used in vivo oxygen amperometry, a proxy for blood oxygen level-dependent (BOLD) signal measurement in human functional magnetic resonance imaging, in rats performing a cued lever-pressing task requiring discrimination between a rewarded and nonrewarded cue. Simultaneous oxygen recordings were obtained from infralimbic PFC (IFC) and NAc throughout both acquisition and extinction of this task. Activation of NAc was specifically observed following rewarded cue onset during the entire acquisition phase and also during the first days of extinction. In contrast, IFC activated only during the earliest periods of acquisition and extinction, more specifically to the nonrewarded cue. Thus, in vivo oxygen amperometry permits a novel, stable form of longitudinal analysis of brain activity in behaving animals, allowing dissociation of the roles of different brain regions over time during learning of reward-driven instrumental action. The present results offer a unique temporal perspective on how NAc may promote actions directed toward anticipated positive outcome throughout learning, while IFC might suppress actions that no longer result in reward, but only during critical periods of learning. PMID:24403158

  5. 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…

  6. 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…

  7. 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…

  8. 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. PMID:25872918

  9. 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.

  10. Learning to live with the Family and Medical Leave Act.

    PubMed

    White, J D

    1994-03-01

    Many issues surround the Family and Medical Leave Act of 1993. Employer concerns focus on eligibility, lost work hours, and the conditions of granting leave. Employees would like to know what their new rights are, how the Act affects their benefits, and what documentation they must present to demonstrate a need for leave. Both agency administrators and home care workers will find clarification here.

  11. 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. PMID:9305467

  12. 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

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

    PubMed

    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

  14. 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

  15. [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.

  16. 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.

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

    PubMed Central

    Torregrossa, Mary M.; Taylor, Jane R.

    2012-01-01

    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 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. PMID:22638814

  18. Blocking NMDA-receptors in the pigeon’s “prefrontal” caudal nidopallium impairs appetitive extinction learning in a sign-tracking paradigm

    PubMed Central

    Lengersdorf, Daniel; Marks, David; Uengoer, Metin; Stüttgen, Maik C.; Güntürkün, Onur

    2015-01-01

    Extinction learning provides the ability to flexibly adapt to new contingencies by learning to inhibit previously acquired associations in a context-dependent manner. The neural networks underlying extinction learning were mostly studied in rodents using fear extinction paradigms. To uncover invariant properties of the neural basis of extinction learning, we employ pigeons as a model system. Since the prefrontal cortex (PFC) of mammals is a key structure for extinction learning, we assessed the role of N-methyl-D-aspartate receptors (NMDARs) in the nidopallium caudolaterale (NCL), the avian functional equivalent of mammalian PFC. Since NMDARs in PFC have been shown to be relevant for extinction learning, we locally antagonized NMDARs through 2-Amino-5-phosphonovalerianacid (APV) during extinction learning in a within-subject sign-tracking ABA-renewal paradigm. APV-injection slowed down extinction learning and in addition also caused a disinhibition of responding to a continuously reinforced control stimulus. In subsequent retrieval sessions, spontaneous recovery was increased while ABA renewal was unaffected. The effect of APV resembles that observed in studies of fear extinction with rodents, suggesting common neural substrates of extinction under both appetitive and aversive conditions and highlighting the similarity of mammalian PFC and the avian caudal nidopallium despite 300 million years of independent evolution. PMID:25918502

  19. Loss of histone deacetylase 2 improves working memory and accelerates extinction learning

    PubMed Central

    Morris, Michael J.; Mahgoub, Melissa; Na, Elisa S.; Pranav, Heena; Monteggia, Lisa. M.

    2013-01-01

    Histone acetylation and deacetylation can be dynamically regulated in response to environmental stimuli and play important roles in learning and memory. Pharmacological inhibition of histone deacetylases (HDACs) improves performance in learning tasks, however these classical agents are ‘pan-HDAC’ inhibitors and their use makes it difficult to determine the roles of specific HDACs in cognitive function. We took a genetic approach using mice lacking the class I HDACs, HDAC1 or HDAC2, in postmitotic forebrain neurons to investigate the specificity or functional redundancy of these HDACs in learning and synaptic plasticity. We show that selective knockout of HDAC2 led to a robust acceleration of the extinction rate of conditioned fear responses and a conditioned taste aversion as well as enhanced performance in an attentional set-shifting task. HDAC2 knockout had no impact on episodic memory or motor learning suggesting that the effects are task-dependent, with the predominant impact of HDAC2 inhibition being an enhancement in an animal’s ability to rapidly adapt its behavioral strategy as a result of changes in associative contingencies. Our results demonstrate that the loss of HDAC2 improves associative learning, with no effect in non-associative learning tasks, suggesting a specific role for HDAC2 in particular types of learning. HDAC2 may be an intriguing target for cognitive and psychiatric disorders that are characterized by an inability to inhibit behavioral responsiveness to maladaptive or no longer relevant associations. PMID:23575838

  20. [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. PMID:25069244

  1. [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.

  2. 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.

  3. 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…

  4. 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. PMID:19430979

  5. 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.

  6. 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.

  7. Individual Differences in the Severely Retarded Child in Acquisition, Stimulus Generalization, and Extinction in Go-No-Go Discrimination Learning

    ERIC Educational Resources Information Center

    Evans, P. L. C.; Hogg, J. H.

    1975-01-01

    This study relates excitatory and inhibitory personality variables of a heterogeneous group of severely retarded children to performance on a discrete trial, successive go-no-go intradimensional discrimination learning problem, which was followed by stimulus generalization tests on a color hue continuum and extinction trials. (GO)

  8. Fear generalization in humans: impact of feature learning on conditioning and extinction.

    PubMed

    Vervliet, Bram; Geens, Maarten

    2014-09-01

    Little is known about the role of discrete stimulus features in the regulation of fear. This study examined the effects of feature learning on the acquisition and extinction of fear conditioning. Human participants were fear conditioned to a yellow triangle (CS+) using an electrical shock. We manipulated feature learning through differential conditioning. The nonconditioned control stimulus (CS-) was a red triangle in one group (Color-Relevant), but a yellow circle in the other group (Shape-Relevant). Next, two generalization stimuli were tested that shared the shape- or color-feature with the CS+ (a blue triangle and a yellow square). Online shock-expectancy ratings and skin conductance responding showed that the CS- determined the pattern of fear generalization: the same-color stimulus elicited more fear in Group Color-Relevant, versus the same-shape stimulus in group Shape-Relevant. Furthermore, extinguishing these two generalization stimuli had no detectable effect on fear of the CS+. These results show that fear generalization is influenced by feature learning through differential conditioning, and that exposures to different features of a stimulus are not sufficient to extinguish fear of that stimulus as a whole.

  9. 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

  10. AX+, BX- discrimination learning in the fear-potentiated startle paradigm: possible relevance to inhibitory fear learning in extinction.

    PubMed

    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.

  11. 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

  12. 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

  13. 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

  14. 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…

  15. Hippocampal Context Processing during Acquisition of a Predictive Learning Task Is Associated with Renewal in Extinction Recall.

    PubMed

    Lissek, Silke; Glaubitz, Benjamin; Schmidt-Wilcke, Tobias; Tegenthoff, Martin

    2016-05-01

    Renewal is defined as the recovery of an extinguished response if extinction and retrieval contexts differ. The context dependency of extinction, as demonstrated by renewal, has important implications for extinction-based therapies. Persons showing renewal (REN) exhibit higher hippocampal activation during extinction in associative learning than those without renewal (NOREN), demonstrating hippocampal context processing, and recruit ventromedial pFC in retrieval. Apart from these findings, brain processes generating renewal remain largely unknown. Conceivably, processing differences in task-relevant brain regions that ultimately lead to renewal may occur already in initial acquisition of associations. Therefore, in two fMRI studies, we investigated overall brain activation and hippocampal activation in REN and NOREN during acquisition of an associative learning task in response to presentation of a context alone or combined with a cue. Results of two studies demonstrated significant activation differences between the groups: In Study 1, a support vector machine classifier correctly assigned participants' brain activation patterns to REN and NOREN groups, respectively. In Study 2, REN and NOREN showed similar hippocampal involvement during context-only presentation, suggesting processing of novelty, whereas overall hippocampal activation to the context-cue compound, suggesting compound encoding, was higher in REN. Positive correlations between hippocampal activation and renewal level indicated more prominent hippocampal processing in REN. Results suggest that hippocampal processing of the context-cue compound rather than of context only during initial learning is related to a subsequent renewal effect. Presumably, REN participants use distinct encoding strategies during acquisition of context-related tasks, which reflect in their brain activation patterns and contribute to a renewal effect. PMID:26807840

  16. 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. PMID:27506654

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

    PubMed

    HOWARTH, C I; DEUTSCH, J A

    1962-07-01

    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. 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.

  19. 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…

  20. Frequency of reinforcement as a determinant of extinction-induced aggression during errorless discrimination learning.

    PubMed

    Rilling, M; Caplan, H J

    1975-01-01

    Seven pigeons were trained to discriminate without errors between a green keylight and a dark key. The key-pecking response was reinforced in the presence of green, and extinction was in effect in the presence of the dark key. The opportunity to attack a restrained target pigeon was present only during extinction. Both variable-interval 30-sec and fixed-ratio 1 schedules of reinforcement during the positive stimulus induced a higher rate of attack during extinction than a variable-interval 5-min schedule. The highest rate of attack during extinction occurred during the first 20 sec after the positive stimulus terminated. Hence, the withdrawal of the positive condition, rather than the consequences of the pecking response during extinction, appears to be one of the primary factors responsible for attack between pigeons during extinction. Behavioral contrast, defined as a decrease in the rate of responding when the positive stimulus was presented alone, was obtained from the four birds that displayed the lowest overall rates of attack while the three birds with the highest attack rates did not display behavioral contrast. For the birds without contrast, components of the attack response during the positive stimulus presumably competed with and reduced the rate of pecking the key, thereby recluding behavioral contrast.

  1. 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

  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. 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…

  4. 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…

  5. 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.

  6. 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.

  7. 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. PMID:26659822

  8. Stimulation of the noradrenergic system during memory formation impairs extinction learning but not the disruption of reconsolidation.

    PubMed

    Soeter, Marieke; Kindt, Merel

    2012-04-01

    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 α(2)-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

  9. 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.

  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. 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…

  12. 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…

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. 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…

  18. 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.

  19. Cognitive Processes in Extinction

    ERIC Educational Resources Information Center

    Lovibond, Peter F.

    2004-01-01

    Human conditioning research shows that learning is closely related to consciously available contingency knowledge, requires attentional resources, and is influenced by language. This research suggests a cognitive model in which extinction consists of changes in contingency beliefs in long-term memory. Laboratory and clinical evidence on extinction…

  20. Extinction with multiple excitors

    PubMed Central

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

    2012-01-01

    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. PMID:23055103

  1. Learning-induced changes in mPFC-BLA connections after fear conditioning, extinction, and reinstatement of fear.

    PubMed

    Vouimba, Rose-Marie; Maroun, Mouna

    2011-10-01

    The neural circuit linking the medial prefrontal cortex (mPFC) and the basolateral amygdala (BLA) has crucial roles in both the acquisition and the extinction of fear. However, the mechanism by which this circuit encodes fear and extinction remains unknown. In this study, we monitored changes in the magnitude of evoked field potentials (EFPs) in the mPFC-BLA and BLA-mPFC pathways following auditory fear conditioning and extinction, in freely moving rats. We report that extinction of fear is mediated by depression of the EFPs in the mPFC-BLA and by potentiation in the reciprocal pathway of BLA-mPFC. Interestingly, reinstatement of fear was associated with recovery of freezing and with reversal of the changes in EFPs that were observed following extinction in both pathways. The findings indicate that the mPFC-BLA circuit expresses differential changes following fear and extinction and point to dynamic and plastic changes underlying fear, extinction, and reinstatement. Manipulations targeting these different types of plasticity could constitute a therapeutic tool for the treatment of anxiety disorders. PMID:21750582

  2. 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…

  3. Extinction in human fear conditioning.

    PubMed

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

    2006-08-15

    Although most extinction research is conducted in animal laboratories, the study of extinction learning in human fear conditioning has gained increasing attention over the last decade. The most important findings from human fear extinction are reviewed in this article. Specifically, we review experimental investigations of the impact of conditioned inhibitors, conditioned exciters, context renewal, and reinstatement on fear extinction in human samples. We discuss data from laboratory studies of the extinction of aversively conditioned stimuli, as well as results from experimental clinical work with fearful or anxious individuals. We present directions for future research, in particular the need for further investigation of differences between animal and human conditioning outcomes, and research examining the role of both automatic and higher-order cognitive processes in human conditioning and extinction.

  4. 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.

  5. 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.

  6. 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. PMID:22465468

  7. Chronic administration of cardanol (ginkgol) extracted from ginkgo biloba leaves and cashew nutshell liquid improves working memory-related learning in rats.

    PubMed

    Tobinaga, Seisho; Hashimoto, Michio; Utsunomiya, Iku; Taguchi, Kyoji; Nakamura, Morihiko; Tsunematsu, Tokugoro

    2012-01-01

    Cardanol (ginkgol) extracted from Ginkgo biloba leaves and cashew nutshell liquid enhances the growth of NSC-34 immortalized motor neuron-like cells and, when chronically administered to young rats, improves working memory-related learning ability as assessed by eight-arm radial maze tasks. These findings suggest that cardanol is one of the components in Ginkgo biloba leaves that improves cognitive learning ability.

  8. 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.

  9. 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

  10. Stress and Fear Extinction.

    PubMed

    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.

  11. Fear extinction in humans: effects of acquisition-extinction delay and masked stimulus presentations.

    PubMed

    Golkar, Armita; Öhman, Arne

    2012-10-01

    Fear extinction can be viewed as an inhibitory learning process. This is supported by post-extinction phenomena demonstrating the return of fear, such as reinstatement. Recent work has questioned this account, claiming that extinction initiated immediately after fear acquisition can abolish the return of fear. In the current study, participants were fear conditioned to four different conditioned stimuli (CS) and underwent extinction either immediately or after a 24 h delay. During extinction, we manipulated CS contingency awareness by presenting two of the CSs (one CS+, one CS-) under non-masked conditions and the other two CSs under masked conditions. Compared to delayed extinction, immediate extinction of non-masked CSs promoted less extinction of fear-potentiated startle and shock expectancy ratings and less reinstatement of fear-potentiated startle without affecting shock expectancy ratings. Critically, future research should clarify how the differences between immediate and delayed extinction in within-session extinction modulate the recovery of fear.

  12. 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.

  13. 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…

  14. 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…

  15. 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…

  16. The Best Distance Learning Graduate Schools: Earning Your Degree without Leaving Home.

    ERIC Educational Resources Information Center

    Phillips, Vicky; Yager, Cindy

    This book profiles 195 accredited institutions that offer graduate degrees via distance learning. The first section of the book examines the following topics of interest to individuals contemplating graduate study through a distance learning program: the increasing numbers of people embarking on graduate study later in life; the quality and…

  17. 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.

  18. 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). PMID:24104049

  19. 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).

  20. Mechanisms of fear extinction.

    PubMed

    Myers, K M; Davis, M

    2007-02-01

    Excessive fear and anxiety are hallmarks of a variety of disabling anxiety disorders that affect millions of people throughout the world. Hence, a greater understanding of the brain mechanisms involved in the inhibition of fear and anxiety is attracting increasing interest in the research community. In the laboratory, fear inhibition most often is studied through a procedure in which a previously fear conditioned organism is exposed to a fear-eliciting cue in the absence of any aversive event. This procedure results in a decline in conditioned fear responses that is attributed to a process called fear extinction. Extensive empirical work by behavioral psychologists has revealed basic behavioral characteristics of extinction, and theoretical accounts have emphasized extinction as a form of inhibitory learning as opposed to an erasure of acquired fear. Guided by this work, neuroscientists have begun to dissect the neural mechanisms involved, including the regions in which extinction-related plasticity occurs and the cellular and molecular processes that are engaged. The present paper will cover behavioral, theoretical and neurobiological work, and will conclude with a discussion of clinical implications.

  1. Genetic gating of human fear learning and extinction: possible implications for gene-environment interaction in anxiety disorder.

    PubMed

    Lonsdorf, Tina B; Weike, Almut I; Nikamo, Pernilla; Schalling, Martin; Hamm, Alfons O; Ohman, Arne

    2009-02-01

    Pavlovian fear conditioning is a widely used model of the acquisition and extinction of fear. Neural findings suggest that the amygdala is the core structure for fear acquisition, whereas prefrontal cortical areas are given pivotal roles in fear extinction. Forty-eight volunteers participated in a fear-conditioning experiment, which used fear potentiation of the startle reflex as the primary measure to investigate the effect of two genetic polymorphisms (5-HTTLPR and COMTval158met) on conditioning and extinction of fear. The 5-HTTLPR polymorphism, located in the serotonin transporter gene, is associated with amygdala reactivity and neuroticism, whereas the COMTval158met polymorphism, which is located in the gene coding for catechol-O-methyltransferase (COMT), a dopamine-degrading enzyme, affects prefrontal executive functions. Our results show that only carriers of the 5-HTTLPR s allele exhibited conditioned startle potentiation, whereas carriers of the COMT met/met genotype failed to extinguish conditioned fear. These results may have interesting implications for understanding gene-environment interactions in the development and treatment of anxiety disorders.

  2. 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…

  3. 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.

  4. 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…

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

    PubMed

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

    2016-01-01

    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. PMID:26555033

  6. Expanding the Intertrial Interval During Extinction: Response Cessation and Recovery

    PubMed Central

    Orinstein, Alyssa J.; Urcelay, Gonzalo P.; Miller, Ralph R.

    2010-01-01

    We examined trial spacing during extinction following a human contingency learning task. Specifically, we assessed if an expanding retrieval practice schedule (Bjork & Bjork, 1992, 2006), in which the spacing between extinction trials was progressively increased, would result in faster immediate extinction and less recovery from extinction than uniformly spaced extinction trials. We used an ABB vs. ABA renewal design and observed that, whereas the expanding group extinguished faster during extinction treatment, the expanding and constant groups showed the same level of extinction with an immediate test in the extinction context (ABB) and the two groups showed equivalent ABA renewal at test in the training context. We conclude that the faster extinction observed in the expanding groups could be misleading in clinical treatment, if the therapist used the absence of fear during extinction as the basis for terminating treatment. PMID:20171324

  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. 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

  9. 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. PMID:24949809

  10. 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,…

  11. 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

  12. 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.

  13. NMDA receptor blockade in the basolateral amygdala disrupts consolidation of stimulus-reward memory and extinction learning during reinstatement of cocaine-seeking in an animal model of relapse

    PubMed Central

    Feltenstein, Matthew W.; See, Ronald E.

    2007-01-01

    Previous research from our laboratory has implicated the basolateral amygdala (BLA) complex in the acquisition and consolidation of cue-cocaine associations, as well as extinction learning, which may regulate the long-lasting control of conditioned stimuli (CS) over drug-seeking behavior. Given the well established role of NMDA glutamate receptor activation in other forms of amygdalar-based learning, we predicted that BLA-mediated drug-cue associative learning would be NMDA receptor dependent. To test this hypothesis, male Sprague-Dawley rats self-administered i.v. cocaine (0.6 mg/kg/infusion) in the absence of explicit CS pairings (2-h sessions, 5 days), followed by a single 1-h classical conditioning (CC) session, during which they received passive infusions of cocaine discretely paired with a light+tone stimulus complex. Following additional cocaine self-administration sessions in the absence of the CS (2-h sessions, 5 days) and extinction training sessions (no cocaine or CS presentation, 2-h sessions, 7 days), the ability of the CS to reinstate cocaine-seeking on three test days was assessed. Rats received bilateral intra-BLA infusions (0.5 μl/hemisphere) of vehicle or the selective NMDA receptor antagonist, 2-amino-5-phosphonovalerate (AP-5), immediately prior to the CC session (acquisition), immediately following the CC session (consolidation), or immediately following reinstatement testing (consolidation of conditioned-cued extinction learning). AP-5 administered before or after CC attenuated subsequent CS-induced reinstatement, whereas AP-5 administered immediately following the first two reinstatement tests impaired the extinction of cocaine-seeking behavior. These results suggest that NMDA receptor-mediated mechanisms within the BLA play a crucial role in the consolidation of drug-CS associations into long-term memories that, in turn, drive cocaine-seeking during relapse. PMID:17613253

  14. Phanerozoic Biodiversity Mass Extinctions

    NASA Astrophysics Data System (ADS)

    Bambach, Richard K.

    2006-05-01

    Recent analyses of Sepkoski's genus-level compendium show that only three events form a statistically separate class of high extinction intensities when only post-Early Ordovician intervals are considered, but geologists have called numerous events mass extinctions. Is this a conflict? A review of different methods of tabulating data from the Sepkoski database reveals 18 intervals during the Phanerozoic have peaks of both magnitude and rate of extinction that appear in each tabulating scheme. These intervals all fit Sepkoski's definition of mass extinction. However, they vary widely in timing and effect of extinction, demonstrating that mass extinctions are not a homogeneous group of events. No consensus has been reached on the kill mechanism for any marine mass extinction. In fact, adequate data on timing in ecologic, rather than geologic, time and on geographic and environmental distribution of extinction have not yet been systematically compiled for any extinction event.

  15. 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.

  16. 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.

  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. [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

  19. 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.

  20. 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.

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

    PubMed

    Robleto, Karla; Thompson, Richard F

    2008-03-01

    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.

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

    PubMed

    Robleto, Karla; Thompson, Richard F

    2008-03-01

    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. PMID:18322108

  3. Repeated valproate treatment facilitates fear extinction under specific stimulus conditions.

    PubMed

    Heinrichs, Stephen C; Leite-Morris, Kimberly A; Rasmusson, Ann M; Kaplan, Gary B

    2013-09-27

    Single dose treatment with histone deacetylase inhibitor (HDACi) agents has been shown to enhance extinction learning in rodent models under certain conditions. The present novel studies were designed to examine the effects of repeated HDACi treatment, with valproate or sodium butyrate, on the extinction of conditioned fear. In Experiments 1 and 2, short duration CS exposure (30s) in combination with vehicle administration progressively attenuated conditioned fear responses over 40 or more sessions. This effective extinction training was not augmented by HDACi treatments. In Experiment 3, we used a long duration CS exposure (120 s) to weaken extinction training. With these extinction parameters, repeated valproate treatment substantially facilitated the acquisition and retention of fear extinction. Results of this study extend previous work suggesting that HDACi's have utility in augmenting the efficiency of fear extinction, although their apparent benefits are critically dependent upon specific parameters of extinction training.

  4. 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

  5. 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.

  6. 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

  7. 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.

  8. 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

  9. 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…

  10. 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

  11. Bimodal extinction without cross-modal extinction.

    PubMed Central

    Inhoff, A W; Rafal, R D; Posner, M J

    1992-01-01

    Three patients with unilateral neurological injury were clinically examined. All showed consistent unilateral extinction in the tactile and visual modalities on simultaneous intramodal stimulation. There was virtually no evidence for cross-modal extinction, however, so that contralateral stimulation of one modality would have extinguished perception of ipsilateral stimuli in the other modality. It is concluded that the attentional system controlling the encoding of tactile and visual stimuli is not unified across the two sensory domains. PMID:1548496

  12. 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'. PMID:22796109

  13. Amphetamine and extinction of cued fear.

    PubMed

    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.

  14. 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

    2016-05-01

    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.

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. 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…

  20. 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.

  1. 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.

  2. Spontaneous recovery from extinction depends on the reconsolidation of the acquisition memory in an appetitive learning paradigm in the honeybee (Apis mellifera).

    PubMed

    Stollhoff, Nicola; Menzel, Randolf; Eisenhardt, Dorothea

    2005-05-01

    Memory retrieval initiates two consolidation processes: consolidation of an extinction memory and reconsolidation of the acquisition memory. The strength of the consolidation processes depends on both the strength of the acquisition memory and the strength of retrieval trials and is correlated with its sensitivity to inhibition. We demonstrate that in the honeybee (Apis mellifera), memory retrieval of a consolidated appetitive olfactory memory leads to both consolidation processes, depending on the number of retrieval trials. Spontaneous recovery from extinction is induced by many (five), but not by few (one and two), retrieval trials. Spontaneous recovery is blocked by emetine, an inhibitor of protein synthesis. We conclude that reconsolidation of the acquisition memory underlies spontaneous recovery.

  3. 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).

  4. 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…

  5. 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. It begins…

  6. [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. PMID:27538279

  7. 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).

  8. 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). PMID:21287312

  9. 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

  10. 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.

  11. 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. PMID:23537484

  12. 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…

  13. 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…

  14. 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

  15. 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…

  16. 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.

  17. Extinction of oscillating populations.

    PubMed

    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. PMID:27078294

  18. 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

  19. 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

  20. Alterations in neuronal morphology in infralimbic cortex predict resistance to fear extinction following acute stress

    PubMed Central

    Moench, Kelly M.; Maroun, Mouna; Kavushansky, Alexandra; Wellman, Cara

    2015-01-01

    Dysfunction in corticolimbic circuits that mediate the extinction of learned fear responses is thought to underlie the perseveration of fear in stress-related psychopathologies, including post-traumatic stress disorder. Chronic stress produces dendritic hypertrophy in basolateral amygdala (BLA) and dendritic hypotrophy in medial prefrontal cortex, whereas acute stress leads to hypotrophy in both BLA and prelimbic cortex. Additionally, both chronic and acute stress impair extinction retrieval. Here, we examined the effects of a single elevated platform stress on extinction learning and dendritic morphology in infralimbic cortex, a region considered to be critical for extinction. Acute stress produced resistance to extinction, as well as dendritic retraction in infralimbic cortex. Spine density on apical and basilar terminal branches was unaffected by stress. However, animals that underwent conditioning and extinction had decreased spine density on apical terminal branches. Thus, whereas dendritic morphology in infralimbic cortex appears to be particularly sensitive to stress, changes in spines may more sensitively reflect learning. Further, in stressed rats that underwent conditioning and extinction, the level of extinction learning was correlated with spine densities, in that rats with poorer extinction retrieval had more immature spines and fewer thin spines than rats with better extinction retrieval, suggesting that stress may have impaired learning-related spine plasticity. These results may have implications for understanding the role of medial prefrontal cortex in learning deficits associated with stress-related pathologies. PMID:26844245

  1. Protein synthesis subserves reconsolidation or extinction depending on reminder duration.

    PubMed

    Pedreira, María Eugenia; Maldonado, Héctor

    2003-06-19

    When learned associations are recalled from long-term memory stores by presentation of an unreinforced conditioned stimulus (CS), two processes are initiated. One, termed reconsolidation, re-activates the association between the conditioned and unconditioned stimuli and transfers it from a stable protein synthesis-independent form of storage to a more labile protein-dependent state. The other is an extinction process in which presentation of the CS alone degrades the association between CS and US. To address the mechanistic relationship between reconsolidation and extinction, we have used an invertebrate model of contextual memory, which involves an association between the learning context and a visual danger stimulus. Here, we show that re-exposure duration to the learning context acts as a switch guiding the memory course toward reconsolidation or extinction, each depending on protein synthesis. Manipulation of this variable allows findings of impaired extinction to be discriminated from those of disrupted reconsolidation.

  2. 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

  3. The transition from memory retrieval to extinction.

    PubMed

    Cammarota, Martín; Barros, Daniela M; Vianna, Mónica R M; Bevilaqua, Lia R M; Coitinho, Adriana; Szapiro, Germán; Izquierdo, Luciana A; Medina, Jorge H; Izquierdo, Iván

    2004-09-01

    Memory is measured by measuring retrieval. Retrieval is often triggered by the conditioned stimulus (CS); however, as known since Pavlov, presentation of the CS alone generates extinction. One-trial avoidance (IA) is a much used conditioned fear paradigm in which the CS is the safe part of a training apparatus, the unconditioned stimulus (US) is a footshock and the conditioned response is to stay in the safe area. In IA, retrieval is measured without the US, as latency to step-down from the safe area (i.e., a platform). Extinction is installed at the moment of the first unreinforced test session, as clearly shown by the fact that many drugs, including PKA, ERK and protein synthesis inhibitors as well as NMDA receptor antagonists, hinder extinction when infused into the hippocampus or the basolateral amygdala at the moment of the first test session but not later. Some, but not all the molecular systems required for extinction are also activated by retrieval, further endorsing the hypothesis that although retrieval is behaviorally and biochemically necessary for the generation of extinction, this last process constitutes a new learning secondary to the unreinforced expression of the original trace.

  4. Retrieval and the extinction of memory.

    PubMed

    Cammarota, Martín; Bevilaqua, Lia R M; Barros, Daniela M; Vianna, Mônica R M; Izquierdo, Luciana A; Medina, Jorge H; Izquierdo, Iván

    2005-06-01

    1. Memory is assessed by measuring retrieval which is often elicited by the solely presentation of the conditioned stimulus (CS). However, as known since Pavlov, presentation of the CS alone generates extinction. 2. One-trial avoidance (IA) is a much used conditioned fear paradigm in which the CS is the safe part of a training apparatus, the unconditioned stimulus (US) is a footshock and the conditioned response (CR) is to stay in the safe area. Retrieval of the memory for the step-down version of this task is measured in the absence of the US, as latency to step-down from the safe area (i.e., a platform). 3. Extinction of the IA response is installed at the moment of the first non-reinforced test session, as clearly shown by the fact that many drugs, including PKA, ERK and protein synthesis inhibitors as well as NMDA receptor antagonists, hinder extinction when infused into the hippocampus or the basolateral amygdala at the moment of the first test session but not later. 4. Some, but not all the molecular systems required for extinction are also activated by retrieval, further endorsing the hypothesis that although retrieval is necessary for the generation of extinction this last process constitutes a new learning secondary to the non-reinforced expression of the original trace.

  5. 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

  6. 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. PMID:25512576

  7. 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.

  8. Hybridization and extinction.

    PubMed

    Todesco, Marco; Pascual, Mariana A; Owens, Gregory L; Ostevik, Katherine L; Moyers, Brook T; Hübner, Sariel; Heredia, Sylvia M; Hahn, Min A; Caseys, Celine; Bock, Dan G; Rieseberg, Loren H

    2016-08-01

    Hybridization may drive rare taxa to extinction through genetic swamping, where the rare form is replaced by hybrids, or by demographic swamping, where population growth rates are reduced due to the wasteful production of maladaptive hybrids. Conversely, hybridization may rescue the viability of small, inbred populations. Understanding the factors that contribute to destructive versus constructive outcomes of hybridization is key to managing conservation concerns. Here, we survey the literature for studies of hybridization and extinction to identify the ecological, evolutionary, and genetic factors that critically affect extinction risk through hybridization. We find that while extinction risk is highly situation dependent, genetic swamping is much more frequent than demographic swamping. In addition, human involvement is associated with increased risk and high reproductive isolation with reduced risk. Although climate change is predicted to increase the risk of hybridization-induced extinction, we find little empirical support for this prediction. Similarly, theoretical and experimental studies imply that genetic rescue through hybridization may be equally or more probable than demographic swamping, but our literature survey failed to support this claim. We conclude that halting the introduction of hybridization-prone exotics and restoring mature and diverse habitats that are resistant to hybrid establishment should be management priorities. PMID:27468307

  9. Cortisol disrupts the neural correlates of extinction recall.

    PubMed

    Kinner, Valerie L; Merz, Christian J; Lissek, Silke; Wolf, Oliver T

    2016-06-01

    The renewal effect describes the recovery of extinguished responses that may occur after a change in context and indicates that extinction memory retrieval is sometimes prone to failure. Stress hormones have been implicated to modulate extinction processes, with mostly impairing effects on extinction retrieval. However, the neurobiological mechanisms mediating stress effects on extinction memory remain elusive. In this functional magnetic resonance imaging study, we investigated the effects of cortisol administration on the neural correlates of extinction memory retrieval in a predictive learning task. In this task, participants were required to predict whether certain food stimuli were associated with stomach trouble when presented in two different contexts. A two-day renewal paradigm was applied in which an association was acquired in context A and subsequently extinguished in context B. On the following day, participants received either cortisol or placebo 40min before extinction memory retrieval was tested in both contexts. Behaviorally, cortisol impaired the retrieval of extinguished associations when presented in the extinction context. On the neural level, this effect was characterized by a reduced context differentiation for the extinguished stimulus in the ventromedial prefrontal cortex, but only in men. In the placebo group, ventromedial prefrontal cortex was functionally connected to the left cerebellum, the anterior cingulate and the right anterior parahippocampal gyrus to express extinction memory. This functional crosstalk was reduced under cortisol. These findings illustrate that the stress hormone cortisol disrupts ventromedial prefrontal cortex functioning and its communication with other brain regions implicated in extinction memory. PMID:26973167

  10. 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.

  11. 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.

  12. 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.

  13. Controversy over mass extinctions

    NASA Astrophysics Data System (ADS)

    Katzoff, Judith A.

    The notion that mass extinctions of species occur at 26-million-year (m.y.) intervals received wide attention in the scientific and popular press a little over a year ago. According to the theory, some sort of periodic extra-terrestrial event had led to the episodes of extinction; comet showers brought on by any of a variety of causes were frequently offered as one explanation.Now the idea is back in the news, this time drawing criticism. An article published in the June 20 issue of Nature criticizes the original analysis, by David Raup and John Sepkoski of the University of Chicago, on the grounds that their data base was overly pared down and that they used a biased definition for mass extinction. Raup and his supporters say that papers now in press will answer the objections.

  14. 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.

  15. Mechanisms governing the reactivation-dependent destabilization of memories and their role in extinction

    PubMed Central

    Flavell, Charlotte R.; Lambert, Elliot A.; Winters, Boyer D.; Bredy, Timothy W.

    2013-01-01

    The extinction of learned associations has traditionally been considered to involve new learning, which competes with the original memory for control over behavior. However, a recent resurgence of interest in reactivation-dependent amnesia has revealed that the retrieval of fear-related memory (with what is essentially a brief extinction session) can result in its destabilization. This review discusses some of the cellular and molecular mechanisms that are involved in the destabilization of a memory following its reactivation and/or extinction, and investigates the evidence that extinction may involve both new learning as well as a partial destabilization-induced erasure of the original memory trace. PMID:24421762

  16. Out with the old and in with the new: Synaptic mechanisms of extinction in the amygdala.

    PubMed

    Maren, Stephen

    2015-09-24

    Considerable research indicates that long-term synaptic plasticity in the amygdala underlies the acquisition of emotional memories, including those learned during Pavlovian fear conditioning. Much less is known about the synaptic mechanisms involved in other forms of associative learning, including extinction, that update fear memories. Extinction learning might reverse conditioning-related changes (e.g., depotentiation) or induce plasticity at inhibitory synapses (e.g., long-term potentiation) to suppress conditioned fear responses. Either mechanism must account for fear recovery phenomena after extinction, as well as savings of extinction after fear recovery. This article is part of a Special Issue entitled SI: Brain and Memory.

  17. 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.

  18. The effects of noradrenergic blockade on extinction in humans.

    PubMed

    Bos, Marieke G N; Beckers, Tom; Kindt, Merel

    2012-03-01

    The process of reconsolidation has attracted much attention because of its potential application for the treatment of psychiatric disorders. Here, we investigate a possible boundary condition of disrupting reconsolidation with the noradrenergic antagonist propranolol in humans. Reconsolidation can be initiated by retrieval of an acquired fear memory, which is in procedure equivalent to extinction training. If memory retrieval promotes the formation of a novel extinction memory trace, propranolol may interfere with extinction rather than with reconsolidation. Using a differential fear conditioning paradigm, we demonstrate that administration of propranolol (double-blind placebo controlled) prior to repetitive unreinforced CS presentations did not affect extinction at a physiological level (startle reflex and skin conductance). At a cognitive level, propranolol directly impaired extinction learning. These findings indicate that careful selection of timing parameters is essential to ensure that pharmacological agents interfere with the intended memory process to reduce fear.

  19. 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…

  20. 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…

  1. 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. PMID:22946817

  2. 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.

  3. 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.

  4. Extinction times in experimental populations.

    PubMed

    Drake, John M

    2006-09-01

    Predicting population extinctions is a key element of quantitative conservation biology and population ecology. Although stochastic population theories have long been used to obtain theoretical distributions of population extinction times, model-based predictions have rarely been tested. Here I report results from a quantitative analysis of extinction time in 281 experimental populations of water fleas (Daphnia magna) in variable environments. To my knowledge, this is the first quantitative estimate of the shape of the distribution of population extinction times based on extinction data for any species. The finding that the distribution of population extinction times was extraordinarily peaked is consistent with theoretical predictions for density-independent populations, but inconsistent with predictions for density-dependent populations. The tail of the extinction time distribution was not exponential. These results imply that our current theories of extinction are inadequate. Future work should focus on how demographic stochasticity scales with population size and effects of nonrandom variable environments on population growth and decline.

  5. Ecology: Dynamics of Indirect Extinction.

    PubMed

    Montoya, Jose M

    2015-12-01

    The experimental identification of the mechanism by which extinctions of predators trigger further predator extinctions emphasizes the role of indirect effects between species in disturbed ecosystems. It also has deep consequences for the hidden magnitude of the current biodiversity crisis.

  6. 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 PMID:26437383

  7. 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.

  8. 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

  9. 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)

  10. 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,…

  11. 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…

  12. Priming and trial spacing in extinction: effects on extinction performance, spontaneous recovery, and reinstatement in appetitive conditioning.

    PubMed

    Moody, Erik W; Sunsay, Ceyhun; Bouton, Mark E

    2006-05-01

    Previous research in this laboratory suggests that priming of the conditional stimulus (CS) in short-term memory may play a role in the trial-spacing effects in appetitive conditioning. For example, a non-reinforced presentation of a CS 60 s before a reinforced trial with the same CS produced slower acquisition than a CS presentation that occurred 240 s before the reinforced trial. The results were consistent with the self-generated priming mechanism proposed by Wagner (e.g., Wagner 1978, 1981). The present experiments extended the earlier work by examining the effects of trial spacing in extinction rather than acquisition. After conditioning with a mixture of intertrial intervals (ITIs), rats received extinction with ITIs of 60 or 240 s, longer or shorter values, or different ways of "chunking" extinction trials in time. Although trial spacing produced effects on extinction performance that were consistent with our previous research on acquisition, there were few long-term differences in spontaneous recovery or in reinstatement. Short ITIs in extinction appear to affect extinction performance more than they affect extinction learning. Mechanisms of trial spacing in conditioning and extinction are discussed.

  13. 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.

  14. 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

  15. 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

  16. 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.

  17. Discreteness induced extinction

    NASA Astrophysics Data System (ADS)

    dos Santos, Renato Vieira; da Silva, Linaena Méricy

    2015-11-01

    Two simple models based on ecological problems are discussed from the point of view of non-equilibrium statistical mechanics. It is shown how discrepant may be the results of the models that include spatial distribution with discrete interactions when compared with the continuous analogous models. In the continuous case we have, under certain circumstances, the population explosion. When we take into account the finiteness of the population, we get the opposite result, extinction. We will analyze how these results depend on the dimension d of the space and describe the phenomenon of the "Discreteness Inducing Extinction" (DIE). The results are interpreted in the context of the "paradox of sex", an old problem of evolutionary biology.

  18. 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.

  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. Extinction rates can be estimated from molecular phylogenies.

    PubMed

    Nee, S; Holmes, E C; May, R M; Harvey, P H

    1994-04-29

    Molecular phylogenies can be used to reject null models of the way we think evolution occurred, including patterns of lineage extinction. They can also be used to provide maximum likelihood estimates of parameters associated with lineage birth and death rates. We illustrate: (i) how molecular phylogenies provide information about the extent to which particular clades are likely to be under threat from extinction; (ii) how cursory analyses of molecular phylogenies can lead to incorrect conclusions about the evolutionary processes that have been at work; and (iii) how different evolutionary processes leave distinctive marks on the structure of reconstructed phylogenies.

  1. 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

  2. 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

  3. A history of corticosterone exposure regulates fear extinction and cortical NR2B, GluR2/3, and BDNF.

    PubMed

    Gourley, Shannon L; Kedves, Alexia T; Olausson, Peter; Taylor, Jane R

    2009-02-01

    A history of exposure to stressors may be a predisposing factor for developing posttraumatic stress disorder (PTSD) after trauma. Extinction of conditioned fear appears to be impaired in PTSD, but the consequences of prior stress or excess glucocorticoid exposure for extinction learning are not known. We report that prior chronic exposure to the stress hormone, corticosterone (CORT), decreases endogenous CORT secretion upon context reexposure and impairs extinction after contextual fear conditioning in rats, while leaving fear memory acquisition and expression intact. Posttraining administration of the glucocorticoid receptor (GR) antagonist, RU38486, partially mimicked prior CORT exposure effects on freezing during fear extinction training. Extinction of conditioned fear is an active learning process thought to involve glutamatergic targets--including specific NMDA and AMPA receptor subunits--in the ventromedial prefrontal cortex (vmPFC), which includes the prelimbic, infralimbic, and medial orbitofrontal cortices. After CORT exposure, decreases in the NMDA receptor NR2B subunit and AMPA receptor subunits, GluR2/3, as well as brain-derived neurotrophic factor, were detected in cortical regions, but not dorsal hippocampus (CA1). Receptor subunit expression levels in the vmPFC correlated with freezing during training. In addition, prior CORT selectively decreased sucrose preference, consistent with established models of anhedonia and with blunted affect in PTSD. Together, these data suggest a cellular mechanism by which chronically elevated glucocorticoid exposure--as may be experienced during repeated exposure to stressors--interferes with the neural systems that modulate behavioral flexibility and may thereby contribute to psychopathological fear states.

  4. 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

    2011-01-01

    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.

  5. 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

    2011-01-01

    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. PMID:22832428

  6. 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

  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.

  8. 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. PMID:27329554

  9. 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

  10. The Memory System Engaged During Acquisition Determines the Effectiveness of Different Extinction Protocols.

    PubMed

    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

  11. 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

  12. Theories of the dorsal bundle extinction effect.

    PubMed

    Mason, S T; Iversen, S D

    1979-07-01

    Selective destruction of the noradrenaline systems in the rat brain using the neurotoxin 6-hydroxydopamine has been found to cause resistance to extinction in a number of behavioural situations. Several theories concerning the behavioural mechanism altered by the lesion, and hence about the role of noradrenaline in normal brain functioning, are proposed and evaluated. Theories suggesting a role for noradrenaline in activity, perseveration, internal inhibition, frustrative non-reward, motivation, or secondary reinforcement, fail to explain all the available evidence and direct tests of each theory fails to support its predictions. A model which suggests that noreadrenaline is involved in attentional behaviour, specifically in filtering out or learning to ignore irrelevant environmental stimuli, is successful in explaining all available data and direct tests of the lesioned rats' attentional capacity serve to confirm many of the predictions of an attentional theory of the dorsal bundle extinction effect.

  13. 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.

  14. 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

  15. 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.

  16. 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

  17. Epigenetics and persistent memory: implications for reconsolidation and silent extinction beyond the zero

    PubMed Central

    Lattal, K Matthew; Wood, Marcelo A

    2013-01-01

    Targeting epigenetic mechanisms during initial learning or memory retrieval can lead to persistent memory. Retrieval induces plasticity that may result in reconsolidation of the original memory, in which critical molecular events are needed to stabilize the memory, or extinction, in which new learning during the retrieval trial creates an additional memory that reflects the changed environmental contingencies. A canonical feature of extinction is that the original response is temporarily suppressed, but returns under various conditions. These characteristics have defined whether a given manipulation alters extinction (when persistence does not occur) or reconsolidation (when persistence does occur). A problem arises with these behavioral definitions when considering the potential for persistent memory of extinction. Recent studies have found that epigenetic modulation of memory processes leads to surprisingly robust and persistent extinction. We discuss evidence from behavioral epigenetic approaches that forces a re-evaluation of widely used behavioral definitions of extinction and reconsolidation. PMID:23354385

  18. Fibroblast growth factor-2 alters the nature of extinction.

    PubMed

    Graham, Bronwyn M; Richardson, Rick

    2011-02-01

    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, do not depend on NMDAr activation. Three experiments demonstrated that FGF2 prevents the switch from NMDAr-dependent to NMDAr-independent reacquisition and re-extinction, suggesting that FGF2 may lead to the partial erasure of the original fear memory. These findings add to a growing body of work suggesting that FGF2 may be a novel pharmacological enhancer of exposure therapy for humans with anxiety disorders.

  19. 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.

  20. 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.

  1. A sequential analysis of the partial reinforcement extinction effect in children*.

    PubMed

    Miyao, G; Meyers, L S

    1973-06-01

    In a series of studies employing children between the ages of 7.6 and 10.6 years of age guessing on a modified Humphreys's board, extinction training was administered following either continuous reinforcement or various schedules of partial reinforcement training. Besides the observation of a partial reinforcement extinction effect, it was found that resistance to extinction appeared to be regulated by those sequential variables specified by extensions of Capaldi's theory of instrumental learning.

  2. The pharmacology of extinction.

    PubMed

    Huxtable, R J

    1992-08-01

    It is impossible to predict what compounds of pharmacological interest may be present in an unexamined species. The extinction of such species may result, therefore, in the loss of therapeutically significant compounds. The fact that science will never know what has been lost does not lessen the significance of the loss. A number of species are discussed to exemplify the potential loss. Ginkgo biloba is an ancient plant, apparently saved from a natural extinction by human intervention. From this tree, the ginkgolides have been isolated. These are potent inhibitors of platelet activating factor and hold promise in the treatment of cerebral ischemia and brain edema. Two species, the tree Taxus brevifolia and the leech Hirudo medicinalis, are threatened as a result of human activity. Both have recently yielded complex compounds of therapeutic importance. The antitumor agent, taxol, is obtained from T. brevifolia and the thrombin inhibitor, hirudin, is found in H. medicinalis. Catharanthus roseus, source of the anticancer agents vincristine and vinblastine, although not threatened, derives from a largely unexamined but severely stressed ecosystem of some 5000 plant species. In other examples, ethnobotanical knowledge of certain plants may be lost while the species survive, as exemplified by the suppression of the Aztec ethnobotany of Mesoamerica by the invading Spanish. Finally, the fallacy of the 'snail darter syndrome', where species may be viewed as too insignificant to worry about, is exposed by consideration of the pharmacological activities of a sea hare (a shell-less marine mollusc) and various leeches.

  3. Regulation of extinction-related plasticity by opioid receptors in the ventrolateral periaqueductal gray matter.

    PubMed

    Parsons, Ryan G; Gafford, Georgette M; Helmstetter, Fred J

    2010-01-01

    Recent work has led to a better understanding of the neural mechanisms underlying the extinction of Pavlovian fear conditioning. Long-term synaptic changes in the medial prefrontal cortex (mPFC) are critical for extinction learning, but very little is currently known about how the mPFC and other brain areas interact during extinction. The current study examined the effect of drugs that impair the extinction of fear conditioning on the activation of the extracellular-related kinase/mitogen-activated protein kinase (ERK/MAPK) in brain regions that likely participate in the consolidation of extinction learning. Inhibitors of opioid and N-methyl-d-aspartic acid (NMDA) receptors were applied to the ventrolateral periaqueductal gray matter (vlPAG) and amygdala shortly before extinction training. Results from these experiments show that blocking opioid receptors in the vlPAG prevented the formation of extinction memory, whereas NMDA receptor blockade had no effect. Conversely, blocking NMDA receptors in the amygdala disrupted the formation of fear extinction memory, but opioid receptor blockade in the same brain area did not. Subsequent experiments tested the effect of these drug treatments on the activation of the ERK/MAPK signaling pathway in various brain regions following extinction training. Only opioid receptor blockade in the vlPAG disrupted ERK phosphorylation in the mPFC and amygdala. These data support the idea that opiodergic signaling derived from the vlPAG affects plasticity across the brain circuit responsible for the formation of extinction memory.

  4. 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.

  5. 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

  6. 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. PMID:22391153

  7. 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

  8. 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.

  9. 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.

  10. 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. PMID:24583374

  11. 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.

  12. Ecology: Dynamics of Indirect Extinction.

    PubMed

    Montoya, Jose M

    2015-12-01

    The experimental identification of the mechanism by which extinctions of predators trigger further predator extinctions emphasizes the role of indirect effects between species in disturbed ecosystems. It also has deep consequences for the hidden magnitude of the current biodiversity crisis. PMID:26654371

  13. Pleistocene extinctions: haunting the survivors.

    PubMed

    Hofreiter, Michael

    2007-08-01

    For many years, the megafaunal extinctions at the end of the Pleistocene have been assumed to have affected only those species that became extinct. However, recent analyses show that the surviving species may also have experienced losses in terms of genetic and ecological diversity. PMID:17686436

  14. 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

  15. 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. PMID:27109918

  16. 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…

  17. 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…

  18. 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…

  19. 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…

  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. 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.

  2. Extinction of Harrington's mountain goat.

    PubMed

    Mead, J I; Martin, P S; Euler, R C; Long, A; Jull, A J; 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.

  3. 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.

  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

    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.

  6. 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.

  7. 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…

  8. 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…

  9. Brain Mechanisms of Extinction of the Classically Conditioned Eyeblink Response

    ERIC Educational Resources Information Center

    Thompson, Richard F.; Robleto, Karla; Poulos, Andrew M.

    2004-01-01

    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 (US). However, brain mechanisms underlying extinction of these responses are still…

  10. Relationship between short- and long-term memory and short- and long-term extinction.

    PubMed

    Cammarota, Martín; Bevilaqua, Lia R M; Rossato, Janine I; Ramirez, Maria; Medina, Jorge H; Izquierdo, Iván

    2005-07-01

    Both the acquisition and the extinction of memories leave short- and long-term mnemonic traces. Here, we show that in male Wistar rats, the short-term memory for a step-down inhibitory avoidance task (IA) is resistant to extinction, and that its expression does not influence retrieval or extinction of long-term memory. It has been known for some time that short- and long-term inhibitory avoidance memory involve separate and parallel processes. Here we show that, instead, short-term extinction of IA long-term memory is the first step towards its long-term extinction, and that this link requires functional NMDA receptors and protein synthesis in the CA1 region of the dorsal hippocampus at the time of the first CS-no US presentation.

  11. Enhanced Extinction of Cocaine Seeking in Brain-derived Neurotrophic Factor Val66Met Knock-In Mice

    PubMed Central

    Briand, Lisa A.; Lee, Francis S.; Blendy, Julie A.; Pierce, R. Christopher

    2013-01-01

    The Val66Met polymorphism in the brain-derived neurotropic factor (BDNF) gene results in alterations in fear extinction behavior in both human populations and mouse models. However, it is not clear whether this polymorphism plays a similar role in extinction of appetitive behaviors. Therefore, we examined operant learning and extinction of both food and cocaine self-administration behavior in an inbred genetic knock-in mouse strain expressing the variant Bdnf. These mice provide a unique opportunity to relate alterations in aversive and appetitive extinction learning as well as provide insight into how human genetic variation can lead to differences in behavior. BDNFMet/Met mice exhibited a severe deficit in operant learning as evidenced by an inability to learn the food self-administration task. Therefore, extinction experiments were performed comparing wildtype (BDNFVal/Val) animals to mice heterozygous for the Met allele (BDNFVal/Met), which did not differ in food or cocaine self-administration behavior. In contrast to the deficit in fear extinction previously demonstrated in these mice, we found that BDNFVal/Met mice exhibited more rapid extinction of cocaine responding compared to wildtype mice. No differences were found between the genotypes in the extinction of food self-administration behavior or the reinstatement of cocaine seeking, indicating the effect is specific to extinction of cocaine responding. These results suggest that the molecular mechanisms underlying aversive and appetitive extinction are distinct from one another and BDNF may play opposing roles in the two phenomena. PMID:22394056

  12. 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. PMID:97707

  13. 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.

  14. 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. PMID:24315832

  15. 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.

  16. 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.

  17. 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.

  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. Hunger promotes fear extinction by activation of an amygdala microcircuit

    PubMed Central

    Lach, Gilliard; Herzog, Herbert; Sperk, Guenther; Tasan, Ramon

    2015-01-01

    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 wildtype 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, while 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

  20. To leave or not to leave.

    PubMed

    Buchan, James

    2016-06-22

    Lies, damned lies and Brexit statistics. It's not been a good month for anyone espousing evidence-based policy and politics after the chair of the Commons health committee switched from Leave to Remain, citing misuse of data by the Leave campaign. PMID:27332589

  1. 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. 

  2. Noradrenergic signaling in infralimbic cortex increases cell excitability and strengthens memory for fear extinction.

    PubMed

    Mueller, Devin; Porter, James T; Quirk, Gregory J

    2008-01-01

    Emotional arousal strengthens memory. This is most apparent in aversive conditioning, in which the stress-related neurotransmitter norepinephrine (NE) enhances associations between sensory stimuli and fear-inducing events. In contrast to conditioning, extinction decreases fear responses, and is thought to form a new memory. It is not known, however, whether NE is necessary for extinction learning. Previous work has shown that the infralimbic prefrontal cortex (IL) is a site of extinction consolidation. Here, we show that blocking noradrenergic beta-receptors in IL before extinction training impaired retrieval of extinction the following day, consistent with a weakened extinction memory. We further found that the sequelae of beta-receptor activation, including protein kinase A (PKA), gene transcription and translation in IL, are necessary for extinction. To determine whether activation of this cascade modulates IL excitability, we measured the response of IL pyramidal neurons to injected current. NE increased the excitability of IL neurons in a beta-receptor- and PKA-dependent manner. We suggest that NE released in IL during fear extinction activates a PKA-mediated molecular cascade that strengthens extinction memory. Thus, emotional arousal evoked by conditioned fear paradoxically promotes the subsequent extinction of that fear, thereby ensuring behavioral flexibility.

  3. Myosin II regulates actin rearrangement-related structural synaptic plasticity during conditioned taste aversion memory extinction.

    PubMed

    Bi, Ai-Ling; Wang, Yue; Zhang, Shuang; Li, Bo-Qin; Sun, Zong-Peng; Bi, Hong-Sheng; Chen, Zhe-Yu

    2015-03-01

    Similar to memory formation, memory extinction is also a new learning process that requires synaptic plasticity. Actin rearrangement is fundamental for synaptic plasticity, however, whether actin rearrangement in the infralimbic cortex (IL) plays a role in memory extinction, as well as the mechanisms underlying it, remains unclear. Here, using a conditioned taste aversion (CTA) paradigm, we demonstrated increased synaptic density and actin rearrangement in the IL during the extinction of CTA. Targeted infusion of an actin rearrangement inhibitor, cytochalasin D, into the IL impaired memory extinction and de novo synapse formation. Notably, we also found increased myosin II phosphorylation in the IL during the extinction of CTA. Microinfusion of a specific inhibitor of the myosin II ATPase, blebbistatin (Blebb), into the IL impaired memory extinction as well as the related actin rearrangement and changes in synaptic density. Moreover, the extinction deficit and the reduction of synaptic density induced by Blebb could be rescued by the actin polymerization stabilizer jasplakinolide (Jasp), suggesting that myosin II acts via actin filament polymerization to stabilize synaptic plasticity during the extinction of CTA. Taken together, we conclude that myosin II may regulate the plasticity of actin-related synaptic structure during memory extinction. Our studies provide a molecular mechanism for understanding the plasticity of actin rearrangement-associated synaptic structure during memory extinction.

  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. PMID:22425782

  5. 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.

  6. Molecular Specificity of Multiple Hippocampal Processes Governing Fear Extinction

    PubMed Central

    Radulovic, Jelena; Tronson, Natalie C.

    2010-01-01

    SYNOPSIS Over many years, fear extinction has been conceptualized as one dominant process, new inhibitory learning, which serves to dampen previously acquired fear. Here we present an alternative view, that brain region-specific processing of representations, expectations and emotional attributes of the fear-provoking event, recruits unique mechanisms that interdependently contribute to the conditioning and extinction of fear. The co-occurrence of these mechanisms within the fear circuit can thus be tracked and differentiated at a molecular and cellular level. Among others, the transcriptional regulators cFos, cAMP-dependent response element binding protein (CREB), Zif268, and extracellular signal-regulated kinases (Erk) stand out as hippocampal nuclear markers signaling novelty, arousal, retrieval, and prediction error, respectively. Consistent with evidence from human studies, these findings indicate that, beyond inhibitory learning, fear extinction requires modification of the emotional attributes and expectations that define the threatening context. Given the likely dysregulation of one or more of these processes in anxiety disorders, a key research challenge for the future is the identification and enhancement of individual extinction mechanisms to target the specific components of fear. Environmental stimuli lacking affective properties (conditioned stimuli, CS) rapidly become threatening if presented with stressful events (unconditioned stimuli, US). Consequently, based on a CS-US association, the presentation of the CS triggers species-specific fear responses until the US consistently stops occurring. At that point, new learning takes place and the fear response declines, a phenomenon termed extinction. The view that extinction occurs because a new, inhibitory CS-noUS association gains control over behavior 106, has remained dominant in the field (reviewed by 20,33,35,100). The implications of impaired fear regulation in the development of anxiety disorders

  7. Facilitation of fear extinction by D-cycloserine: theoretical and clinical implications.

    PubMed

    Richardson, Rick; Ledgerwood, Lana; Cranney, Jacquelyn

    2004-01-01

    Anxiety disorders are among the most common psychological disturbances in the industrialized world. Current behavioral therapy procedures for these disorders are somewhat effective, but their efficacy could be substantially improved. Because these procedures are largely based on the process of extinction, manipulations that enhance extinction may lead to improvements in treatment effectiveness. We review the evidence that D-cycloserine (DCS), a partial NMDA agonist, facilitates extinction of learned fear in rats. Although only a few studies have examined the effects of DCS on extinction of learned fear, this work suggests that this drug may have a number of potential clinical benefits. In addition, attempts at interpreting this research illustrate our limited understanding of the processes involved in extinction.

  8. Stochastic models of population extinction.

    PubMed

    Ovaskainen, Otso; Meerson, Baruch

    2010-11-01

    Theoretical ecologists have long sought to understand how the persistence of populations depends on biotic and abiotic factors. Classical work showed that demographic stochasticity causes the mean time to extinction to increase exponentially with population size, whereas variation in environmental conditions can lead to a power-law scaling. Recent work has focused especially on the influence of the autocorrelation structure ('color') of environmental noise. In theoretical physics, there is a burst of research activity in analyzing large fluctuations in stochastic population dynamics. This research provides powerful tools for determining extinction times and characterizing the pathway to extinction. It yields, therefore, sharp insights into extinction processes and has great potential for further applications in theoretical biology.

  9. 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)

  10. 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.

  11. 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).

  12. Mass extinctions: Ecological diversity maintained

    NASA Astrophysics Data System (ADS)

    Aberhan, Martin

    2014-03-01

    The end-Permian extinction decimated marine life on an unprecedented scale. However, an analysis of the lifestyles of the surviving genera shows that very little functional diversity was lost at the sea floor.

  13. 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.

  14. 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;…

  15. Extinction and the associative structure of heterogeneous instrumental chains.

    PubMed

    Thrailkill, Eric A; Bouton, Mark E

    2016-09-01

    Drug abuse, overeating, and smoking are all examples of instrumental behaviors that often involve chains or sequences of behavior. A behavior chain is minimally composed of a procurement response that is required in order for a subsequent consumption response to be reinforced. Despite the translational importance of behavior chains, few studies have attempted to understand what binds them together and takes them apart. This article surveys the development of the heterogeneous instrumental chain method and introduces recent findings that have used extinction to analyze the associative content of (what is learned in) the chain. Chained responses that are occasion-set by their own discriminative stimuli may be directly associated; extinction of the procurement response weakens its associated consumption response, and extinction of the consumption response weakens its associated procurement response. Extinction itself involves learning to inhibit the response. Extinguished chained responses are subject to renewal when they are tested either back in the acquisition context or in a new context. In addition, a consumption response that is extinguished outside its chain is renewed when returned to the context of the preceding response in the chain. Research on heterogeneous behavior chains can provide important insights into an important but often overlooked aspect of instrumental learning.

  16. Extinction and the associative structure of heterogeneous instrumental chains.

    PubMed

    Thrailkill, Eric A; Bouton, Mark E

    2016-09-01

    Drug abuse, overeating, and smoking are all examples of instrumental behaviors that often involve chains or sequences of behavior. A behavior chain is minimally composed of a procurement response that is required in order for a subsequent consumption response to be reinforced. Despite the translational importance of behavior chains, few studies have attempted to understand what binds them together and takes them apart. This article surveys the development of the heterogeneous instrumental chain method and introduces recent findings that have used extinction to analyze the associative content of (what is learned in) the chain. Chained responses that are occasion-set by their own discriminative stimuli may be directly associated; extinction of the procurement response weakens its associated consumption response, and extinction of the consumption response weakens its associated procurement response. Extinction itself involves learning to inhibit the response. Extinguished chained responses are subject to renewal when they are tested either back in the acquisition context or in a new context. In addition, a consumption response that is extinguished outside its chain is renewed when returned to the context of the preceding response in the chain. Research on heterogeneous behavior chains can provide important insights into an important but often overlooked aspect of instrumental learning. PMID:27296700

  17. 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

  18. A model of mass extinction.

    PubMed

    Newman, M E

    1997-12-01

    In the last few years a number of authors have suggested that evolution may be a so-called self-organized critical phenomenon, and that critical processes might have a significant effect on the dynamics of ecosystems. In particular it has been suggested that mass extinction may arise through a purely biotic mechanism as the result of "coevolutionary avalanches". In this paper we first explore the empirical evidence which has been put forward in favor of this conclusion. The data center principally around the existence of power-law functional forms in the distribution of the sizes of extinction events and other quantities. We then propose a new mathematical model of mass extinction which does not rely on coevolutionary effects and in which extinction is caused entirely by the action of environmental stress on species. In combination with a simple model of species adaption we show that this process can account for all the observed data without the need to invoke coevolution and critical processes. The model also makes some independent predictions, such as the existence of "aftershock" extinctions in the aftermath of large mass extinction events, which should in theory be testable against the fossil record.

  19. 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

  20. 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. PMID:20152889

  1. 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.

  2. 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

  3. 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

  4. 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

  5. The Class I HDAC inhibitor RGFP963 enhances consolidation of cued fear extinction

    PubMed Central

    Bowers, Mallory E.; Xia, Bing; Carreiro, Samantha

    2015-01-01

    Evidence indicates that broad, nonspecific histone deacetylase (HDAC) inhibition enhances learning and memory, however, the contribution of the various HDACs to specific forms of learning is incompletely understood. Here, we show that the Class I HDAC inhibitor, RGFP963, enhances consolidation of cued fear extinction. However, RGFP966, a strong inhibitor of HDAC3, does not significantly enhance consolidation of cued fear extinction. These data extend previous evidence that demonstrate the Class I HDACs play a role in the consolidation of long-term memory, suggesting that HDAC1 and/or HDAC2, but less likely HDAC3, may function as negative regulators of extinction retention. The development of specific HDAC inhibitors, such as RGFP963, will further illuminate the role of specific HDACs in various types of learning and memory. Moreover, HDAC inhibitors that enhance cued fear extinction may show translational promise for the treatment of fear-related disorders, including post-traumatic stress disorder (PTSD). PMID:25776040

  6. 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. PMID:23948212

  7. The entorhinal cortex plays a role in extinction.

    PubMed

    Bevilaqua, Lia R; Bonini, Juliana S; Rossato, Janine I; Izquierdo, Luciana A; Cammarota, Martín; Izquierdo, Iván

    2006-03-01

    In this study, we analyzed the participation of the entorhinal cortex in extinction of a learned aversive response. Rats with infusion cannulae aimed to the entorhinal cortex were trained in a one-trial step-down inhibitory avoidance task (IA) and submitted to four consecutive daily test sessions without the footshock, a procedure that induced extinction of the conditioned response in control animals. When infused into the entorhinal cortex immediately after the first extinction session at doses able to block consolidation of IA memory, the NMDA receptor antagonist, AP5 (25 nmol/side), the inhibitor of protein synthesis anisomycin (300 nmol/side) and the inhibitor of CaMKII, KN-93 (10 nmol/side), but not the MEK1/2 inhibitor PD-98059 (5 nmol/side) hindered extinction of the IA response. The same results were obtained when the interval between the first and second test session was 48 instead of 24h. The data indicate that normal functionality of the NMDA receptors, together with CaMKII activity and protein synthesis are necessary in the entorhinal cortex at the time of the first test session to generate extinction. Our results also suggest that the ERK1/2 pathway does not play a role in this process.

  8. 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.

  9. 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.

  10. How partial reinforcement of food cues affects the extinction and reacquisition of appetitive responses. A new model for dieting success?

    PubMed

    van den Akker, Karolien; Havermans, Remco C; Bouton, Mark E; Jansen, Anita

    2014-10-01

    Animals and humans can easily learn to associate an initially neutral cue with food intake through classical conditioning, but extinction of learned appetitive responses can be more difficult. Intermittent or partial reinforcement of food cues causes especially persistent behaviour in animals: after exposure to such learning schedules, the decline in responding that occurs during extinction is slow. After extinction, increases in responding with renewed reinforcement of food cues (reacquisition) might be less rapid after acquisition with partial reinforcement. In humans, it may be that the eating behaviour of some individuals resembles partial reinforcement schedules to a greater extent, possibly affecting dieting success by interacting with extinction and reacquisition. Furthermore, impulsivity has been associated with less successful dieting, and this association might be explained by impulsivity affecting the learning and extinction of appetitive responses. In the present two studies, the effects of different reinforcement schedules and impulsivity on the acquisition, extinction, and reacquisition of appetitive responses were investigated in a conditioning paradigm involving food rewards in healthy humans. Overall, the results indicate both partial reinforcement schedules and, possibly, impulsivity to be associated with worse extinction performance. A new model of dieting success is proposed: learning histories and, perhaps, certain personality traits (impulsivity) can interfere with the extinction and reacquisition of appetitive responses to food cues and they may be causally related to unsuccessful dieting.

  11. 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.

  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. PMID:25065505

  13. 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.

  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. Infralimbic EphB2 Modulates Fear Extinction in Adolescent Rats.

    PubMed

    Cruz, Emmanuel; Soler-Cedeño, Omar; Negrón, Geovanny; Criado-Marrero, Marangelie; Chompré, Gladys; Porter, James T

    2015-09-01

    Adolescent rats are prone to impaired fear extinction, suggesting that mechanistic differences in extinction could exist in adolescent and adult rats. Since the infralimbic cortex (IL) is critical for fear extinction, we used PCR array technology to identify gene expression changes in IL induced by fear extinction in adolescent rats. Interestingly, the ephrin type B receptor 2 (EphB2), a tyrosine kinase receptor associated with synaptic development, was downregulated in IL after fear extinction. Consistent with the PCR array results, EphB2 levels of mRNA and protein were reduced in IL after fear extinction compared with fear conditioning, suggesting that EphB2 signaling in IL regulates fear extinction memory in adolescents. Finally, reducing EphB2 synthesis in IL with shRNA accelerated fear extinction learning in adolescent rats, but not in adult rats. These findings identify EphB2 in IL as a key regulator of fear extinction during adolescence, perhaps due to the increase in synaptic remodeling occurring during this developmental phase. PMID:26354908

  16. Differential participation of temporal structures in the consolidation and reconsolidation of taste aversion extinction.

    PubMed

    Garcia-Delatorre, Paola; Rodríguez-Ortiz, Carlos J; Balderas, Israela; Bermúdez-Rattoni, Federico

    2010-09-01

    The extinction process has been described as the decline in the frequency or intensity of the conditioned response following the withdrawal of reinforcement. Hence, experimental extinction does not reflect loss of the original memory, but rather reflects new learning, which in turn requires consolidation in order to be maintained in the long term. During extinction of conditioned taste aversion (CTA), a taste previously associated with aversive consequences acquires a safe status through continuous presentations of the flavor with no aversive consequence. In addition, reconsolidation has been defined as the labile state of a consolidated memory after its reactivation by the presentation of relevant information. In this study, we analyzed structures from the temporal lobe that could be involved in consolidation and reconsolidation of extinction of CTA by means of new protein synthesis. Our results showed that protein synthesis in the hippocampus (HC), the perirhinal cortex (PR) and the insular cortex (IC) of rats participate in extinction consolidation, whereas the basolateral amygdala plays no part in this phenomenon. Furthermore, we found that inhibition of protein synthesis in the IC in a third extinction trial had an effect on reconsolidation of extinction. The participation of the HC in taste memory has been described as a downmodulator for CTA consolidation, and has been related to a context-taste association. Altogether, these data suggest that extinction of aversive taste memories are subserved by the IC, HC and PR, and that extinction can undergo reconsolidation, a process depending only on the IC.

  17. Infralimbic EphB2 Modulates Fear Extinction in Adolescent Rats.

    PubMed

    Cruz, Emmanuel; Soler-Cedeño, Omar; Negrón, Geovanny; Criado-Marrero, Marangelie; Chompré, Gladys; Porter, James T

    2015-09-01

    Adolescent rats are prone to impaired fear extinction, suggesting that mechanistic differences in extinction could exist in adolescent and adult rats. Since the infralimbic cortex (IL) is critical for fear extinction, we used PCR array technology to identify gene expression changes in IL induced by fear extinction in adolescent rats. Interestingly, the ephrin type B receptor 2 (EphB2), a tyrosine kinase receptor associated with synaptic development, was downregulated in IL after fear extinction. Consistent with the PCR array results, EphB2 levels of mRNA and protein were reduced in IL after fear extinction compared with fear conditioning, suggesting that EphB2 signaling in IL regulates fear extinction memory in adolescents. Finally, reducing EphB2 synthesis in IL with shRNA accelerated fear extinction learning in adolescent rats, but not in adult rats. These findings identify EphB2 in IL as a key regulator of fear extinction during adolescence, perhaps due to the increase in synaptic remodeling occurring during this developmental phase.

  18. Infralimbic EphB2 Modulates Fear Extinction in Adolescent Rats

    PubMed Central

    Cruz, Emmanuel; Soler-Cedeño, Omar; Negrón, Geovanny; Criado-Marrero, Marangelie; Chompré, Gladys

    2015-01-01

    Adolescent rats are prone to impaired fear extinction, suggesting that mechanistic differences in extinction could exist in adolescent and adult rats. Since the infralimbic cortex (IL) is critical for fear extinction, we used PCR array technology to identify gene expression changes in IL induced by fear extinction in adolescent rats. Interestingly, the ephrin type B receptor 2 (EphB2), a tyrosine kinase receptor associated with synaptic development, was downregulated in IL after fear extinction. Consistent with the PCR array results, EphB2 levels of mRNA and protein were reduced in IL after fear extinction compared with fear conditioning, suggesting that EphB2 signaling in IL regulates fear extinction memory in adolescents. Finally, reducing EphB2 synthesis in IL with shRNA accelerated fear extinction learning in adolescent rats, but not in adult rats. These findings identify EphB2 in IL as a key regulator of fear extinction during adolescence, perhaps due to the increase in synaptic remodeling occurring during this developmental phase. PMID:26354908

  19. FAAH inhibitor, URB-597, promotes extinction and CB(1) antagonist, SR141716, inhibits extinction of conditioned aversion produced by naloxone-precipitated morphine withdrawal, but not extinction of conditioned preference produced by morphine in rats.

    PubMed

    Manwell, Laurie A; Satvat, Elham; Lang, Stefan T; Allen, Craig P; Leri, Francesco; Parker, Linda A

    2009-11-01

    Converging evidence suggests that the endogenous cannabinoid (eCB) system is involved in extinction of learned behaviours. Using operant and classical conditioning procedures, the potential of the fatty acid amide (FAAH) inhibitor, URB-597, and the CB(1) antagonist/inverse agonist, SR141716, to promote and inhibit (respectively) extinction of learned responses previously motivated by either rewarding or aversive stimuli was investigated. In the operant conditioning procedure (Expt. 1), rats previously trained to lever press for sucrose reward were administered URB-597 (0.3 mg/kg) or the CB(1) antagonist/inverse agonist SR141716 (2.5 mg/kg) prior to each of three extinction trials. In the conditioned floor preference procedure (Expts 2a-d), rats trained to associate morphine with one of two distinctive floors were administered one of several doses of the CB(1) antagonist/inverse agonist, AM-251 (Expt 2a) or URB-597 (Expt 2b and 2d) prior to each extinction/test trial wherein a choice of both floors was presented and prior to forced exposure to each floor (Expt 2c). In the conditioned floor aversion procedure (Expt. 3), rats trained to associate a naloxone-precipitated morphine withdrawal with a floor cue were administered URB-597 or SR141716 prior to each of 24 extinction/testing trials. URB-597 did not promote and SR141716 did not reduce extinction rates for sucrose reward-induced operant responding (Expt. 1) or morphine-induced conditioned floor preference (Expts. 2a-d). In contrast, URB-597 facilitated, whereas SR141716 impaired, extinction of the conditioned floor aversion (Expt. 3). These data support previous reports that the eCB system selectively facilitates extinction of aversive memories. URB-597 may prove useful in targeting extinction of aversively motivated behaviours.

  20. C57BL/6J and DBA/2J mice differ in extinction and renewal of extinguished conditioned fear.

    PubMed

    Waddell, Jaylyn; Dunnett, Claire; Falls, William A

    2004-10-01

    While a number of studies have examined the acquisition and expression of conditioned fear in inbred mice, very few have examined extinction of conditioned fear in inbred mice and few attempts have been made to compare extinction learning between inbred strains. Because inbred strains differ in a number of physiological and biochemical variables, differences in extinction learning may provide insight into the genetic influence of extinction learning. The purpose of this study was to examine extinction and renewal of conditioned fear in two common inbred strains of mice. C57BL/6J and DBA/2J mice were conditioned with pairings of either a tone or light and foot shock in a single session. On the following 4 days, mice were given extinction training, consisting of tone or light alone trials (Experiment 1A). C57 mice exhibited robust spontaneous recovery between sessions, but did extinguish both within and between sessions. DBA mice extinguished more quickly relative to C57 mice, and this extinction was stable between sessions (i.e., DBA mice did not exhibit spontaneous recovery). The rapid loss of fear in DBA relative to C57 mice was extinction-dependent and not merely due to poor long-term memory (Experiment 1B). Renewal testing (Experiment 2) replicated the strain difference in extinction and also showed that DBA mice have a deficit in the context specificity of extinction. C57 mice, but not DBA mice showed renewal of extinguished fear when tested in a context different from the one in which extinction training took place. These data suggest that the nature of extinction learning is influenced by characteristics of the inbred mouse strain.

  1. Evidence for recovery of fear following immediate extinction in rats and humans

    PubMed Central

    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 demonstrating that fear can recover following extinction. However, a recent report by Myers and coworkers suggests that extinction conducted immediately after fear learning may erase or prevent the consolidation of the fear memory trace. Since extinction is a major component of nearly all behavioral therapies for human fear disorders, this finding supports the notion that therapeutic intervention beginning very soon after a traumatic event will be more efficacious. Given the importance of this issue, and the controversy regarding immediate versus delayed therapeutic interventions, we examined two fear recovery phenomena in both rats and humans: spontaneous recovery (SR) and reinstatement. We found evidence for SR and reinstatement in both rats and humans even when extinction was conducted immediately after fear learning. Thus, our data do not support the hypothesis that immediate extinction erases the original memory trace, nor do they suggest that a close temporal proximity of therapeutic intervention to the traumatic event might be advantageous. PMID:18509113

  2. Retrieval and Reconsolidation Accounts of Fear Extinction

    PubMed Central

    Ponnusamy, Ravikumar; Zhuravka, Irina; Poulos, Andrew M.; Shobe, Justin; Merjanian, Michael; Huang, Jeannie; Wolvek, David; O’Neill, Pia-Kelsey; Fanselow, Michael S.

    2016-01-01

    Extinction is the primary mode for the treatment of anxiety disorders. However, extinction memories are prone to relapse. For example, fear is likely to return when a prolonged time period intervenes between extinction and a subsequent encounter with the fear-provoking stimulus (spontaneous recovery). Therefore there is considerable interest in the development of procedures that strengthen extinction and to prevent such recovery of fear. We contrasted two procedures in rats that have been reported to cause such deepened extinction. One where extinction begins before the initial consolidation of fear memory begins (immediate extinction) and another where extinction begins after a brief exposure to the consolidated fear stimulus. The latter is thought to open a period of memory vulnerability similar to that which occurs during initial consolidation (reconsolidation update). We also included a standard extinction treatment and a control procedure that reversed the brief exposure and extinction phases. Spontaneous recovery was only found with the standard extinction treatment. In a separate experiment we tested fear shortly after extinction (i.e., within 6 h). All extinction procedures, except reconsolidation update reduced fear at this short-term test. The findings suggest that strengthened extinction can result from alteration in both retrieval and consolidation processes. PMID:27242459

  3. Baclofen facilitates the extinction of methamphetamine-induced conditioned place preference in rats.

    PubMed

    Voigt, Robin M; Herrold, Amy A; Napier, T Celeste

    2011-04-01

    The powerful, long-lasting association between the rewarding effects of a drug and contextual cues associated with drug administration can be studied using conditioned place preference (CPP). The GABA(B) receptor agonist baclofen facilitates the extinction of morphine-induced CPP in mice. The current study extended this work by determining if baclofen could enhance the extinction of methamphetamine (Meth) CPP. CPP was established using a six-day conditioning protocol wherein Meth-pairings were alternated with saline-pairings. Rats were subsequently administered baclofen (2 mg/kg i.p. or vehicle) immediately after each daily forced extinction session, which consisted of a saline injection immediately prior to being placed into the previously Meth- or saline-paired chamber. One extinction training cycle, consisted of six once-daily forced extinction sessions, mimicking the alternating procedure established during conditioning, followed by a test for preference (Ext test). CPP persisted for at least four extinction cycles in vehicle-treated rats. In contrast, CPP was inhibited following a single extinction training cycle. These data indicate that Meth-induced CPP was resistant to extinction, but extinction training was rendered effective when the training was combined with baclofen. These findings converge with the prior demonstration of baclofen facilitating the extinction of morphine-induced CPP indicating that GABA(B) receptor actions are independent of the primary (unconditioned) stimulus (i.e., the opiate or the stimulant) and likely reflect mechanisms engaged by extinction learning processes per se. Thus, baclofen administered in conjunction with extinction training may be of value for addiction therapy regardless of the class of drug being abused.

  4. Infectious disease, endangerment, and extinction.

    PubMed

    Macphee, Ross D E; Greenwood, Alex D

    2013-01-01

    Infectious disease, especially virulent infectious disease, is commonly regarded as a cause of fluctuation or decline in biological populations. However, it is not generally considered as a primary factor in causing the actual endangerment or extinction of species. We review here the known historical examples in which disease has, or has been assumed to have had, a major deleterious impact on animal species, including extinction, and highlight some recent cases in which disease is the chief suspect in causing the outright endangerment of particular species. We conclude that the role of disease in historical extinctions at the population or species level may have been underestimated. Recent methodological breakthroughs may lead to a better understanding of the past and present roles of infectious disease in influencing population fitness and other parameters. PMID:23401844

  5. Speeding up spontaneous disease extinction

    NASA Astrophysics Data System (ADS)

    Khasin, Michael

    2012-02-01

    The dynamics of epidemic in a susceptible population is affected both by the random character of interactions between the individuals and by environmental variations. As a consequence, the sizes of the population groups (infected, susceptible, etc.) fluctuate in the course of evolution of the epidemic. In a small community a rare large fluctuation in the number of infected can result in extinction of the disease. We suggest a novel paradigm of controlling the epidemic, where the control field, such as vaccination, is designed to maximize the rate of spontaneous disease extinction. We show that, for a limited-scope vaccination, the optimal vaccination protocol and its impact on the epidemics have universal features: (i) the vaccine must be applied in pulses, (ii) the spontaneous disease extinction is synchronized with the vaccination. We trace this universality to general properties of the response of large fluctuations to external perturbations.

  6. Extinction risk of soil biota

    PubMed Central

    Veresoglou, Stavros D.; Halley, John M.; Rillig, Matthias C.

    2015-01-01

    No species lives on earth forever. Knowing when and why species go extinct is crucial for a complete understanding of the consequences of anthropogenic activity, and its impact on ecosystem functioning. Even though soil biota play a key role in maintaining the functioning of ecosystems, the vast majority of existing studies focus on aboveground organisms. Many questions about the fate of belowground organisms remain open, so the combined effort of theorists and applied ecologists is needed in the ongoing development of soil extinction ecology. PMID:26593272

  7. Extinct radionuclides. [in solar system

    NASA Technical Reports Server (NTRS)

    Podosek, F. A.; Swindle, T. D.

    1988-01-01

    Extinct radionuclides, or radioactive isotopes with lifetimes of the order of 1 to 100 Myr that are now extinct in the solar system are discussed. Evidence is presented for the presence of such radionuclides in the early solar system, including Al-26, Mn-53, Pd-107, I-129, Pu-244, and Sm-146. It is suggested that the abundances of these species provide constraints on nucleosynthetic time scales and the history of solar system materials before they became the solar system. The shortest-lived species is Al-26, which may have been sufficiently abundant to be the major heat source for meteorite parent-body metamorphism or igneous differentiation.

  8. Star formation and extinct radioactivities

    NASA Technical Reports Server (NTRS)

    Cameron, A. G. W.

    1984-01-01

    An assessment is made of the evidence for the existence of now-extinct radioactivities in primitive solar system material, giving attention to implications for the early stages of sun and solar system formation. The characteristics of possible disturbances in dense molecular clouds which can initiate the formation of cloud cores is discussed, with emphasis on these disturbances able to generate fresh radioactivities. A one-solar mass red giant star on the asymptotic giant branch appears to have been the best candidate to account for the short-lived extinct radioactivities in the early solar system.

  9. Extinction risk of soil biota.

    PubMed

    Veresoglou, Stavros D; Halley, John M; Rillig, Matthias C

    2015-01-01

    No species lives on earth forever. Knowing when and why species go extinct is crucial for a complete understanding of the consequences of anthropogenic activity, and its impact on ecosystem functioning. Even though soil biota play a key role in maintaining the functioning of ecosystems, the vast majority of existing studies focus on aboveground organisms. Many questions about the fate of belowground organisms remain open, so the combined effort of theorists and applied ecologists is needed in the ongoing development of soil extinction ecology.

  10. Extinction risk of soil biota.

    PubMed

    Veresoglou, Stavros D; Halley, John M; Rillig, Matthias C

    2015-01-01

    No species lives on earth forever. Knowing when and why species go extinct is crucial for a complete understanding of the consequences of anthropogenic activity, and its impact on ecosystem functioning. Even though soil biota play a key role in maintaining the functioning of ecosystems, the vast majority of existing studies focus on aboveground organisms. Many questions about the fate of belowground organisms remain open, so the combined effort of theorists and applied ecologists is needed in the ongoing development of soil extinction ecology. PMID:26593272

  11. The effects of verbal instruction on affective and expectancy learning.

    PubMed

    Lipp, Ottmar V; Mallan, Kimberley M; Libera, Marilia; Tan, Mingshen

    2010-03-01

    The current research assessed the effects of verbal instruction on affective and expectancy learning during repeated contingency reversals (Experiment 1) and during extinction (Experiment 2) in a picture-picture paradigm. Affective and expectancy learning displayed contingency reversal and extinction, but changes were slower for affective learning. Instructions facilitated reversal and extinction of expectancy learning but did not impact on affective learning. These findings suggest a differential susceptibility of affective and expectancy learning to verbal instruction and question previous reports that verbal instructions can accelerate the extinction of non-prepared fear learning in humans. PMID:19945093

  12. Noradrenergic blockade stabilizes prefrontal activity and enables fear extinction under stress.

    PubMed

    Fitzgerald, Paul J; Giustino, Thomas F; Seemann, Jocelyn R; Maren, Stephen

    2015-07-14

    Stress-induced impairments in extinction learning are believed to sustain posttraumatic stress disorder (PTSD). Noradrenergic signaling may contribute to extinction impairments by modulating medial prefrontal cortex (mPFC) circuits involved in fear regulation. Here we demonstrate that aversive fear conditioning rapidly and persistently alters spontaneous single-unit activity in the prelimbic and infralimbic subdivisions of the mPFC in behaving rats. These conditioning-induced changes in mPFC firing were mitigated by systemic administration of propranolol (10 mg/kg, i.p.), a β-noradrenergic receptor antagonist. Moreover, propranolol administration dampened the stress-induced impairment in extinction observed when extinction training is delivered shortly after fear conditioning. These findings suggest that β-adrenoceptors mediate stress-induced changes in mPFC spike firing that contribute to extinction impairments. Propranolol may be a helpful adjunct to behavioral therapy for PTSD, particularly in patients who have recently experienced trauma.

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

    ERIC Educational Resources Information Center

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

    2012-01-01

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

  14. Modeling Population Growth and Extinction

    ERIC Educational Resources Information Center

    Gordon, Sheldon P.

    2009-01-01

    The exponential growth model and the logistic model typically introduced in the mathematics curriculum presume that a population grows exclusively. In reality, species can also die out and more sophisticated models that take the possibility of extinction into account are needed. In this article, two extensions of the logistic model are considered,…

  15. Novelty-facilitated extinction: Providing a novel outcome in place of an expected threat diminishes recovery of defensive responses

    PubMed Central

    Dunsmoor, Joseph E.; Campese, Vinn D.; Ceceli, Ahmet O.; LeDoux, Joseph E.; Phelps, Elizabeth A.

    2015-01-01

    Background Experimental extinction serves as a model for psychiatric treatments based on associative learning. However, the effects of extinction are often transient, as evidenced by post-extinction return of defensive behaviors. From a therapeutic perspective, an inherent problem with extinction may be that mere omission of threat is not sufficient to reduce future threat uncertainty. The current study tested an augmented form of extinction that replaced- rather than merely omitted- expected threat outcomes with novel non-threat outcomes, with the goal of reducing post-extinction return of defensive behaviors. Methods Thirty-two healthy male Sprague-Dawley rats and 47 human adults underwent threat conditioning to a conditioned stimulus paired with an electrical shock. Subjects then underwent a standard extinction protocol with shock omitted, or an augmented extinction protocol wherein the shock was replaced by a surprising tone. Tests of post-extinction recovery occurred 24 hours later in the absence of the tone. Results Replacing the shock with a novel non-threat outcome, as compared to shock omission, reduced post-extinction recovery (freezing in rats and anticipatory skin conductance responses in humans) when tested 24 hours later. Self-reported intolerance of uncertainty was positively correlated with recovery following standard extinction in humans, providing new evidence that post-extinction recovery is related to sensitivity to future threat uncertainty. Conclusions These findings provide cross-species evidence of a novel strategy to enhance extinction that may have broad implications for how to override associative learning that has become maladaptive, and offer a simple technique that could be straightforwardly adapted and implemented in clinical situations. PMID:25636175

  16. A parametric analysis of factors affecting acquisition and extinction of contextual fear in C57BL/6 and DBA/2 mice.

    PubMed

    Lattal, K Matthew; Maughan, Deeanna K

    2012-05-01

    Behavioral analyses of genetically modified and inbred strains of mice have revealed neural systems and molecules that are involved in memory formation. Many of these studies have examined memories that form in contextual fear conditioning, in which an organism learns that a particular context signals the occurrence of a footshock. During fear extinction, nonreinforced exposure to the context results in the loss of the conditioned fear response. The study of extinction has been instrumental for behavioral and molecular theories of memory. However, many of the transgenic, knockout, and inbred strains of mice that have been widely studied in memory have behavioral deficits in contextual fear conditioning, which makes the study of extinction in these mice particularly challenging. Here we explore several strategies for studying extinction in C57BL/6 and DBA/2 mice, two strains known to differ in contextual fear conditioning. First, we attempt to equate performance prior to extinction through several extensive conditioning protocols. Second, we examine extinction in subsets of mice matched for initial levels of context conditioning. Third, we examine within-strain effects of variables known to affect extinction. Differences between the strains persisted across extensive conditioning and extinction protocols, but both strains were sensitive to session duration and context manipulations during extinction. We describe the implications of our results for behavioral and neurobiological approaches to extinction, and we examine the general challenges in studying extinction in subjects that differ in learning or performance prior to extinction.

  17. Problematising Early School Leaving

    ERIC Educational Resources Information Center

    Ross, Alistair; Leathwood, Carole

    2013-01-01

    Early school leaving has been identified as a key policy priority across Europe. In this article, we critically discuss the underpinning assumptions and rationale for this policy focus, challenging the association that is made between early school leaving, economic growth and employment. We suggest that ESL is important, not because it is…

  18. Emotional perseveration: an update on prefrontal-amygdala interactions in fear extinction.

    PubMed

    Sotres-Bayon, Francisco; Bush, David E A; LeDoux, Joseph E

    2004-01-01

    Fear extinction refers to the ability to adapt as situations change by learning to suppress a previously learned fear. This process involves a gradual reduction in the capacity of a fear-conditioned stimulus to elicit fear by presenting the conditioned stimulus repeatedly on its own. Fear extinction is context-dependent and is generally considered to involve the establishment of inhibitory control of the prefrontal cortex over amygdala-based fear processes. In this paper, we review research progress on the neural basis of fear extinction with a focus on the role of the amygdala and the prefrontal cortex. We evaluate two competing hypotheses for how the medial prefrontal cortex inhibits amygdala output. In addition, we present new findings showing that lesions of the basal amygdala do not affect fear extinction. Based on this result, we propose an updated model for integrating hippocampal-based contextual information with prefrontal-amygdala circuitry.

  19. D-cycloserine and the facilitation of extinction of conditioned fear: consequences for reinstatement.

    PubMed

    Ledgerwood, Lana; Richardson, Rick; Cranney, Jacquelyn

    2004-06-01

    Several recent studies have reported that D-cycloserine (DCS), a partial N-methyl-D-aspartate agonist, facilitates extinction of learned fear in rats. Other studies have shown that representation of the unconditioned stimulus (US) can reinstate learned fear after extinction. This study examined whether this reinstatement effect occurs in Sprague-Dawley rats given DCS at the time of extinction. Results showed that saline-treated rats exhibited the reinstatement effect but DCS-treated rats did not (Experiments 1 and 2). This lack of reinstatement in DCS-treated rats was not due to residual effects of DCS on either US or context processing (Experiment 3). Overall, these results (a) raise questions about the mechanisms underlying DCS facilitation of extinction and (b) suggest that DCS might have substantial practical benefit.

  20. The Geochemistry of Mass Extinction

    NASA Astrophysics Data System (ADS)

    Kump, L. R.

    2003-12-01

    The course of biological evolution is inextricably linked to that of the environment through an intricate network of feedbacks that span all scales of space and time. Disruptions to the environment have biological consequences, and vice versa. Fossils provide the prima facie evidence for biotic disruptions: catastrophic losses of global biodiversity at various times in the Phanerozoic. However, the forensic evidence for the causes and environmental consequences of these mass extinctions resides primarily in the geochemical composition of sedimentary rocks deposited during the extinction intervals. Thus, advancement in our understanding of mass extinctions requires detailed knowledge obtained from both paleontological and geochemical records.This chapter reviews the state of knowledge concerning the geochemistry of the "big five" extinctions of the Phanerozoic (e.g., Sepkoski, 1993): the Late Ordovician (Hirnantian; 440 Ma), the Late Devonian (an extended or multiple event with its apex at the Frasnian-Famennian (F-F) boundary; 367 Ma), the Permian-Triassic (P-Tr; 251 Ma), the Triassic-Jurassic (Tr-J; 200 Ma), and the Cretaceous-Tertiary (K-T; 65 Ma). The focus on the big five is a matter of convenience, as there is a continuum in extinction rates from "background" to "mass extinction." Although much of the literature on extinctions centers on the causes and extents of biodiversity loss, in recent years paleontologists have begun to focus on recoveries (see, e.g., Hart, 1996; Kirchner and Weil, 2000; Erwin, 2001 and references therein).To the extent that the duration of the recovery interval may reflect a slow relaxation of the environment from perturbation, analysis of the geochemical record of recovery is an integral part of this effort. In interpreting the geochemical and biological records of recovery, we need to maintain a clear distinction among the characteristics of the global biota: their biodiversity (affected by differences in origination and extinction

  1. EARTH SCIENCE: Did Volcanoes Drive Ancient Extinctions?

    PubMed

    Kerr, R A

    2000-08-18

    With the publication in recent weeks of two papers on a mass extinction 183 million years ago, researchers can add five suggestive cases to the list of extinctions with known causes. These extinctions coincide with massive outpourings of lava, accompanied by signs that global warming threw the ocean-atmosphere system out of whack. Although no one can yet pin any of these mass extinctions with certainty on the volcanic eruptions, scientists say it's unlikely that they're all coincidences.

  2. FROM THE NEUROBIOLOGY OF EXTINCTION TO IMPROVED CLINICAL TREATMENTS

    PubMed Central

    Morrison, Filomene G.; Ressler, Kerry J.

    2015-01-01

    The neural circuitry underlying the fear response is extremely well conserved across mammalian species, which has allowed for the rapid translation of research findings in rodent models of fear to therapeutic interventions in human populations. Many aspects of exposure-based psychotherapy treatments in humans, which are widely used in the treatment of PTSD, panic disorder, phobias, and other anxiety disorders, are closely paralleled by extinction training in rodent fear conditioning models. Here, we discuss how the neural circuitry of fear learning and extinction in rodent animal models may be used to understand the underlying neural circuitry of fear-related disorders, such as PTSD in humans. We examine the factors that contribute to the pathology and development of PTSD. Next, we will review how fear is measured in animal models using classical Pavlovian fear conditioning paradigms, as well as brain regions such as the amygdala, which are involved in the fear response across species. Finally, we highlight the following three systems involved in the extinction of fear, all of which represent promising avenues for therapeutic interventions in the clinic: (1) the role of the glutamatergic N-methyl-d-aspartate (NMDA) receptor, (2) the role of the brain-derived neurotrophic factor (BDNF)–tyrosine kinase B (TrkB) induced signaling pathway, and (3) the role of the renin-angiotensin system. The modulation of pathways underlying fear learning and extinction, such as the ones presented in this review, in combination with extinction-based exposure therapy, represents promising avenues for therapeutic intervention in the treatment of human fear related disorders. PMID:24254958

  3. Uncertainty-Dependent Extinction of Fear Memory in an Amygdala-mPFC Neural Circuit Model.

    PubMed

    Li, Yuzhe; Nakae, Ken; Ishii, Shin; Naoki, Honda

    2016-09-01

    Uncertainty of fear conditioning is crucial for the acquisition and extinction of fear memory. Fear memory acquired through partial pairings of a conditioned stimulus (CS) and an unconditioned stimulus (US) is more resistant to extinction than that acquired through full pairings; this effect is known as the partial reinforcement extinction effect (PREE). Although the PREE has been explained by psychological theories, the neural mechanisms underlying the PREE remain largely unclear. Here, we developed a neural circuit model based on three distinct types of neurons (fear, persistent and extinction neurons) in the amygdala and medial prefrontal cortex (mPFC). In the model, the fear, persistent and extinction neurons encode predictions of net severity, of unconditioned stimulus (US) intensity, and of net safety, respectively. Our simulation successfully reproduces the PREE. We revealed that unpredictability of the US during extinction was represented by the combined responses of the three types of neurons, which are critical for the PREE. In addition, we extended the model to include amygdala subregions and the mPFC to address a recent finding that the ventral mPFC (vmPFC) is required for consolidating extinction memory but not for memory retrieval. Furthermore, model simulations led us to propose a novel procedure to enhance extinction learning through re-conditioning with a stronger US; strengthened fear memory up-regulates the extinction neuron, which, in turn, further inhibits the fear neuron during re-extinction. Thus, our models increased the understanding of the functional roles of the amygdala and vmPFC in the processing of uncertainty in fear conditioning and extinction. PMID:27617747

  4. Uncertainty-Dependent Extinction of Fear Memory in an Amygdala-mPFC Neural Circuit Model

    PubMed Central

    Li, Yuzhe; Nakae, Ken; Ishii, Shin; Naoki, Honda

    2016-01-01

    Uncertainty of fear conditioning is crucial for the acquisition and extinction of fear memory. Fear memory acquired through partial pairings of a conditioned stimulus (CS) and an unconditioned stimulus (US) is more resistant to extinction than that acquired through full pairings; this effect is known as the partial reinforcement extinction effect (PREE). Although the PREE has been explained by psychological theories, the neural mechanisms underlying the PREE remain largely unclear. Here, we developed a neural circuit model based on three distinct types of neurons (fear, persistent and extinction neurons) in the amygdala and medial prefrontal cortex (mPFC). In the model, the fear, persistent and extinction neurons encode predictions of net severity, of unconditioned stimulus (US) intensity, and of net safety, respectively. Our simulation successfully reproduces the PREE. We revealed that unpredictability of the US during extinction was represented by the combined responses of the three types of neurons, which are critical for the PREE. In addition, we extended the model to include amygdala subregions and the mPFC to address a recent finding that the ventral mPFC (vmPFC) is required for consolidating extinction memory but not for memory retrieval. Furthermore, model simulations led us to propose a novel procedure to enhance extinction learning through re-conditioning with a stronger US; strengthened fear memory up-regulates the extinction neuron, which, in turn, further inhibits the fear neuron during re-extinction. Thus, our models increased the understanding of the functional roles of the amygdala and vmPFC in the processing of uncertainty in fear conditioning and extinction. PMID:27617747

  5. Uncertainty-Dependent Extinction of Fear Memory in an Amygdala-mPFC Neural Circuit Model.

    PubMed

    Li, Yuzhe; Nakae, Ken; Ishii, Shin; Naoki, Honda

    2016-09-01

    Uncertainty of fear conditioning is crucial for the acquisition and extinction of fear memory. Fear memory acquired through partial pairings of a conditioned stimulus (CS) and an unconditioned stimulus (US) is more resistant to extinction than that acquired through full pairings; this effect is known as the partial reinforcement extinction effect (PREE). Although the PREE has been explained by psychological theories, the neural mechanisms underlying the PREE remain largely unclear. Here, we developed a neural circuit model based on three distinct types of neurons (fear, persistent and extinction neurons) in the amygdala and medial prefrontal cortex (mPFC). In the model, the fear, persistent and extinction neurons encode predictions of net severity, of unconditioned stimulus (US) intensity, and of net safety, respectively. Our simulation successfully reproduces the PREE. We revealed that unpredictability of the US during extinction was represented by the combined responses of the three types of neurons, which are critical for the PREE. In addition, we extended the model to include amygdala subregions and the mPFC to address a recent finding that the ventral mPFC (vmPFC) is required for consolidating extinction memory but not for memory retrieval. Furthermore, model simulations led us to propose a novel procedure to enhance extinction learning through re-conditioning with a stronger US; strengthened fear memory up-regulates the extinction neuron, which, in turn, further inhibits the fear neuron during re-extinction. Thus, our models increased the understanding of the functional roles of the amygdala and vmPFC in the processing of uncertainty in fear conditioning and extinction.

  6. [Aversive effects of halothane anesthesia in the rat, using extinction of tasks by positive reinforcement].

    PubMed

    Gisquet-Verrier, P; Alexinsky, T; Deweer, B

    1977-10-17

    Immediate posttrial halothane anaesthesia accelerates the extinction of two previously acquired operant tasks--barpress learning or modified K-maze learning. This acceleration is not due to any motor impairment. These results are not consistent with the hypothesis of amnestic effects of halothane anaesthesia; they are interpreted in terms of aversive effects.

  7. The Effects of Partial Reinforcement in the Acquisition and Extinction of Recurrent Serial Patterns.

    ERIC Educational Resources Information Center

    Dockstader, Steven L.

    The purpose of these 2 experiments was to determine whether sequential response pattern behavior is affected by partial reinforcement in the same way as other behavior systems. The first experiment investigated the partial reinforcement extinction effects (PREE) in a sequential concept learning task where subjects were required to learn a…

  8. The Class I HDAC Inhibitor RGFP963 Enhances Consolidation of Cued Fear Extinction

    ERIC Educational Resources Information Center

    Bowers, Mallory E.; Xia, Bing; Carreiro, Samantha; Ressler, Kerry J.

    2015-01-01

    Evidence indicates that broad, nonspecific histone deacetylase (HDAC) inhibition enhances learning and memory, however, the contribution of the various HDACs to specific forms of learning is incompletely understood. Here, we show that the Class I HDAC inhibitor, RGFP963, enhances consolidation of cued fear extinction. However, RGFP966, a strong…

  9. From lab to clinic: Extinction of cued cravings to reduce overeating.

    PubMed

    Jansen, Anita; Schyns, Ghislaine; Bongers, Peggy; van den Akker, Karolien

    2016-08-01

    Food cue reactivity is a strong motivation to eat, even in the absence of hunger. Therefore, food cue reactivity might sabotage healthy eating, induce weight gain and impede weight loss or weight maintenance. Food cue reactivity can be learned via Pavlovian appetitive conditioning: It is easily acquired but the extinction of appetitive responding seems to be more challenging. Several properties of extinction make it fragile: extinction does not erase the original learning and extinction is context-dependent. These properties threaten full extinction and increase the risk of full relapse. Extinction procedures are discussed to reduce or prevent the occurrence of rapid reacquisition, spontaneous recovery, renewal and reinstatement after extinction. A translation to food cue exposure treatment is made and suggestions are provided, such as conducting the exposure in relevant contexts, using occasional reinforcement and targeting expectancy violation instead of habituation. A new hypothesis proposed here is that the adding of inhibition training to strengthen inhibition skills that reduce instrumental responding, might be beneficial to improve food cue exposure effects. PMID:26994737

  10. Computational search for hypotheses concerning the endocannabinoid contribution to the extinction of fear conditioning.

    PubMed

    Anastasio, Thomas J

    2013-01-01

    Fear conditioning, in which a cue is conditioned to elicit a fear response, and extinction, in which a previously conditioned cue no longer elicits a fear response, depend on neural plasticity occurring within the amygdala. Projection neurons in the basolateral amygdala (BLA) learn to respond to the cue during fear conditioning, and they mediate fear responding by transferring cue signals to the output stage of the amygdala. Some BLA projection neurons retain their cue responses after extinction. Recent work shows that activation of the endocannabinoid system is necessary for extinction, and it leads to long-term depression (LTD) of the GABAergic synapses that inhibitory interneurons make onto BLA projection neurons. Such GABAergic LTD would enhance the responses of the BLA projection neurons that mediate fear responding, so it would seem to oppose, rather than promote, extinction. To address this paradox, a computational analysis of two well-known conceptual models of amygdaloid plasticity was undertaken. The analysis employed exhaustive state-space search conducted within a declarative programming environment. The analysis reveals that GABAergic LTD actually increases the number of synaptic strength configurations that achieve extinction while preserving the cue responses of some BLA projection neurons in both models. The results suggest that GABAergic LTD helps the amygdala retain cue memory during extinction even as the amygdala learns to suppress the previously conditioned response. The analysis also reveals which features of both models are essential for their ability to achieve extinction with some cue memory preservation, and suggests experimental tests of those features.

  11. From lab to clinic: Extinction of cued cravings to reduce overeating.

    PubMed

    Jansen, Anita; Schyns, Ghislaine; Bongers, Peggy; van den Akker, Karolien

    2016-08-01

    Food cue reactivity is a strong motivation to eat, even in the absence of hunger. Therefore, food cue reactivity might sabotage healthy eating, induce weight gain and impede weight loss or weight maintenance. Food cue reactivity can be learned via Pavlovian appetitive conditioning: It is easily acquired but the extinction of appetitive responding seems to be more challenging. Several properties of extinction make it fragile: extinction does not erase the original learning and extinction is context-dependent. These properties threaten full extinction and increase the risk of full relapse. Extinction procedures are discussed to reduce or prevent the occurrence of rapid reacquisition, spontaneous recovery, renewal and reinstatement after extinction. A translation to food cue exposure treatment is made and suggestions are provided, such as conducting the exposure in relevant contexts, using occasional reinforcement and targeting expectancy violation instead of habituation. A new hypothesis proposed here is that the adding of inhibition training to strengthen inhibition skills that reduce instrumental responding, might be beneficial to improve food cue exposure effects.

  12. Role of Dopamine 2 Receptor in Impaired Drug-Cue Extinction in Adolescent Rats

    PubMed Central

    Zbukvic, Isabel C.; Ganella, Despina E.; Perry, Christina J.; Madsen, Heather B.; Bye, Christopher R.; Lawrence, Andrew J.; Kim, Jee Hyun

    2016-01-01

    Adolescent drug users display resistance to treatment such as cue exposure therapy (CET), as well as increased liability to relapse. The basis of CET is extinction learning, which involves dopamine signaling in the medial prefrontal cortex (mPFC). This system undergoes dramatic alterations during adolescence. Therefore, we investigated extinction of a cocaine-associated cue in adolescent and adult rats. While cocaine self-administration and lever-alone extinction were not different between the two ages, we observed that cue extinction reduced cue-induced reinstatement in adult but not adolescent rats. Infusion of the selective dopamine 2 receptor (D2R)-like agonist quinpirole into the infralimbic cortex (IL) of the mPFC prior to cue extinction significantly reduced cue-induced reinstatement in adolescents. This effect was replicated by acute systemic treatment with the atypical antipsychotic aripiprazole (Abilify), a partial D2R-like agonist. These data suggest that adolescents may be more susceptible to relapse due to a deficit in cue extinction learning, and highlight the significance of D2R signaling in the IL for cue extinction during adolescence. These findings inspire new tactics for improving adolescent CET, with aripiprazole representing an exciting potential pharmacological adjunct for behavioral therapy. PMID:26946126

  13. Computational search for hypotheses concerning the endocannabinoid contribution to the extinction of fear conditioning

    PubMed Central

    Anastasio, Thomas J.

    2013-01-01

    Fear conditioning, in which a cue is conditioned to elicit a fear response, and extinction, in which a previously conditioned cue no longer elicits a fear response, depend on neural plasticity occurring within the amygdala. Projection neurons in the basolateral amygdala (BLA) learn to respond to the cue during fear conditioning, and they mediate fear responding by transferring cue signals to the output stage of the amygdala. Some BLA projection neurons retain their cue responses after extinction. Recent work shows that activation of the endocannabinoid system is necessary for extinction, and it leads to long-term depression (LTD) of the GABAergic synapses that inhibitory interneurons make onto BLA projection neurons. Such GABAergic LTD would enhance the responses of the BLA projection neurons that mediate fear responding, so it would seem to oppose, rather than promote, extinction. To address this paradox, a computational analysis of two well-known conceptual models of amygdaloid plasticity was undertaken. The analysis employed exhaustive state-space search conducted within a declarative programming environment. The analysis reveals that GABAergic LTD actually increases the number of synaptic strength configurations that achieve extinction while preserving the cue responses of some BLA projection neurons in both models. The results suggest that GABAergic LTD helps the amygdala retain cue memory during extinction even as the amygdala learns to suppress the previously conditioned response. The analysis also reveals which features of both models are essential for their ability to achieve extinction with some cue memory preservation, and suggests experimental tests of those features. PMID:23761759

  14. Determining Extinction Ratio Of A Laser Diode

    NASA Technical Reports Server (NTRS)

    Unger, Glenn L.

    1992-01-01

    Improved technique to determine extinction ratio of pulsed laser diode based partly on definition of extinction ratio applicable to nonideal laser pulses. Heretofore, determinations involved assumption of ideal laser pulses, and neglected optical power from background light. Because power fluctuates during real pulse, more realistic to define extinction ratio in terms of energy obtained.

  15. Further Evidence of Auditory Extinction in Aphasia

    ERIC Educational Resources Information Center

    Marshall, Rebecca Shisler; Basilakos, Alexandra; Love-Myers, Kim

    2013-01-01

    Purpose: Preliminary research ( Shisler, 2005) suggests that auditory extinction in individuals with aphasia (IWA) may be connected to binding and attention. In this study, the authors expanded on previous findings on auditory extinction to determine the source of extinction deficits in IWA. Method: Seventeen IWA (M[subscript age] = 53.19 years)…

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

    PubMed

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

    2014-07-01

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

  17. Are Isolated Indigenous Populations Headed toward Extinction?

    PubMed

    Walker, Robert S; Kesler, Dylan C; Hill, Kim R

    2016-01-01

    At least 50 indigenous groups spread across lowland South America remain isolated and have only intermittent and mostly hostile interactions with the outside world. Except in emergency situations, the current policy of governments in Brazil, Colombia, and Peru towards isolated tribes is a "leave them alone" strategy, in which isolated groups are left uncontacted. However, these no-contact policies are based on the assumption that isolated populations are healthy and capable of persisting in the face of mounting external threats, and that they can maintain population viability in the long-term. Here, we test this assumption by tracking the sizes and movements of cleared horticultural areas made by 8 isolated groups over the last 10-14 years. We used deforestation data derived from remote sensing Landsat satellite sensors to identify clearings, and those were then validated and assessed with high-resolution imagery. We found only a single example of a relatively large and growing population (c. 50 cleared ha and 400 people), whereas all of the other 7 groups exhibited much smaller villages and gardens with no sizable growth through time. These results indicated that the smaller groups are critically endangered, and it prompts an urgent re-thinking of policies toward isolated populations, including plans for well-organized contacts that may help save lives and rescue isolated indigenous populations from imminent extinction.

  18. Are Isolated Indigenous Populations Headed toward Extinction?

    PubMed Central

    Walker, Robert S.; Kesler, Dylan C.; Hill, Kim R.

    2016-01-01

    At least 50 indigenous groups spread across lowland South America remain isolated and have only intermittent and mostly hostile interactions with the outside world. Except in emergency situations, the current policy of governments in Brazil, Colombia, and Peru towards isolated tribes is a “leave them alone” strategy, in which isolated groups are left uncontacted. However, these no-contact policies are based on the assumption that isolated populations are healthy and capable of persisting in the face of mounting external threats, and that they can maintain population viability in the long-term. Here, we test this assumption by tracking the sizes and movements of cleared horticultural areas made by 8 isolated groups over the last 10–14 years. We used deforestation data derived from remote sensing Landsat satellite sensors to identify clearings, and those were then validated and assessed with high-resolution imagery. We found only a single example of a relatively large and growing population (c. 50 cleared ha and 400 people), whereas all of the other 7 groups exhibited much smaller villages and gardens with no sizable growth through time. These results indicated that the smaller groups are critically endangered, and it prompts an urgent re-thinking of policies toward isolated populations, including plans for well-organized contacts that may help save lives and rescue isolated indigenous populations from imminent extinction. PMID:26954672

  19. Are Isolated Indigenous Populations Headed toward Extinction?

    PubMed

    Walker, Robert S; Kesler, Dylan C; Hill, Kim R

    2016-01-01

    At least 50 indigenous groups spread across lowland South America remain isolated and have only intermittent and mostly hostile interactions with the outside world. Except in emergency situations, the current policy of governments in Brazil, Colombia, and Peru towards isolated tribes is a "leave them alone" strategy, in which isolated groups are left uncontacted. However, these no-contact policies are based on the assumption that isolated populations are healthy and capable of persisting in the face of mounting external threats, and that they can maintain population viability in the long-term. Here, we test this assumption by tracking the sizes and movements of cleared horticultural areas made by 8 isolated groups over the last 10-14 years. We used deforestation data derived from remote sensing Landsat satellite sensors to identify clearings, and those were then validated and assessed with high-resolution imagery. We found only a single example of a relatively large and growing population (c. 50 cleared ha and 400 people), whereas all of the other 7 groups exhibited much smaller villages and gardens with no sizable growth through time. These results indicated that the smaller groups are critically endangered, and it prompts an urgent re-thinking of policies toward isolated populations, including plans for well-organized contacts that may help save lives and rescue isolated indigenous populations from imminent extinction. PMID:26954672

  20. Effects of reinforcement schedule on facilitation of operant extinction by chlordiazepoxide.

    PubMed

    Leslie, Julian C; Shaw, David; Gregg, Gillian; McCormick, Nichola; Reynolds, David S; Dawson, Gerard R

    2005-11-01

    Learning and memory are central topics in behavioral neuroscience, and inbred mice strains are widely investigated. However, operant conditioning techniques are not as extensively used in this field as they should be, given the effectiveness of the methodology of the experimental analysis of behavior. In the present study, male C57B1/6 mice, widely used as background for transgenic studies, were trained to lever press on discrete-trial fixed-ratio 5 or fixed-interval (11 s or 31 s) schedules of food reinforcement and then exposed to 15 extinction sessions following vehicle or chlordiazepoxide injections (15 mg/kg i.p., administered either prior to all extinction sessions, or prior to the final 10 extinction sessions). Extinction of operant behavior was facilitated by drug administration following training on either schedule, but this facilitation only occurred once a number of extinction sessions had taken place. The extinction process proceeded more rapidly following fixed-interval training. Resistance to extinction was equally high following training with either schedule type, and was reduced by drug administration in both cases. These phenomena were evident in individual cumulative records and in analyses of group data. Results are interpreted in terms of phenomena of operant extinction identified in Skinner's (1938) Behavior of Organisms, and by behavioral momentum theory. These procedures could be used to extend the contribution of operant conditioning to contemporary behavioral neuroscience. PMID:16596968

  1. Involvement of the basolateral amygdala in muscarinic cholinergic modulation of extinction memory consolidation.

    PubMed

    Boccia, Mariano M; Blake, Mariano G; Baratti, Carlos M; McGaugh, James L

    2009-01-01

    Previous studies have reported that drugs affecting neuromodulatory systems within the basolateral amygdala (BLA), including drugs affecting muscarinic cholinergic receptors, modulate the consolidation of many kinds of training, including contextual fear conditioning (CFC). The present experiments investigated the involvement of muscarinic cholinergic influences within the BLA in modulating the consolidation of CFC extinction memory. Male Sprague Dawley rats implanted with unilateral cannula aimed at the BLA were trained on a CFC task, using footshock stimulation, and 24 and 48 h later were given extinction training by replacing them in the apparatus without footshock. Following each extinction session they received intra-BLA infusions of the cholinergic agonist oxotremorine (10 ng). Immediate post-extinction BLA infusions significantly enhanced extinction but infusions administered 180 min after extinction training did not influence extinction. Thus the oxotremorine effects were time-dependent and not attributable to non-specific effects on retention performance. These findings provide evidence that, as previously found with original CFC learning, cholinergic activation within the BLA modulates the consolidation of CFC extinction. PMID:18706510

  2. Effects of reinforcement schedule on facilitation of operant extinction by chlordiazepoxide.

    PubMed

    Leslie, Julian C; Shaw, David; Gregg, Gillian; McCormick, Nichola; Reynolds, David S; Dawson, Gerard R

    2005-11-01

    Learning and memory are central topics in behavioral neuroscience, and inbred mice strains are widely investigated. However, operant conditioning techniques are not as extensively used in this field as they should be, given the effectiveness of the methodology of the experimental analysis of behavior. In the present study, male C57B1/6 mice, widely used as background for transgenic studies, were trained to lever press on discrete-trial fixed-ratio 5 or fixed-interval (11 s or 31 s) schedules of food reinforcement and then exposed to 15 extinction sessions following vehicle or chlordiazepoxide injections (15 mg/kg i.p., administered either prior to all extinction sessions, or prior to the final 10 extinction sessions). Extinction of operant behavior was facilitated by drug administration following training on either schedule, but this facilitation only occurred once a number of extinction sessions had taken place. The extinction process proceeded more rapidly following fixed-interval training. Resistance to extinction was equally high following training with either schedule type, and was reduced by drug administration in both cases. These phenomena were evident in individual cumulative records and in analyses of group data. Results are interpreted in terms of phenomena of operant extinction identified in Skinner's (1938) Behavior of Organisms, and by behavioral momentum theory. These procedures could be used to extend the contribution of operant conditioning to contemporary behavioral neuroscience.

  3. Deep brain stimulation of the ventral striatum enhances extinction of conditioned fear.

    PubMed

    Rodriguez-Romaguera, Jose; Do Monte, Fabricio H M; Quirk, Gregory J

    2012-05-29

    Deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) reduces symptoms of intractable obsessive-compulsive disorder (OCD), but the mechanism of action is unknown. OCD is characterized by avoidance behaviors that fail to extinguish, and DBS could act, in part, by facilitating extinction of fear. We investigated this possibility by using auditory fear conditioning in rats, for which the circuits of fear extinction are well characterized. We found that DBS of the VS (the VC/VS homolog in rats) during extinction training reduced fear expression and strengthened extinction memory. Facilitation of extinction was observed for a specific zone of dorsomedial VS, just above the anterior commissure; stimulation of more ventrolateral sites in VS impaired extinction. DBS effects could not be obtained with pharmacological inactivation of either dorsomedial VS or ventrolateral VS, suggesting an extrastriatal mechanism. Accordingly, DBS of dorsomedial VS (but not ventrolateral VS) increased expression of a plasticity marker in the prelimbic and infralimbic prefrontal cortices, the orbitofrontal cortex, the amygdala central nucleus (lateral division), and intercalated cells, areas known to learn and express extinction. Facilitation of fear extinction suggests that, in accord with clinical observations, DBS could augment the effectiveness of cognitive behavioral therapies for OCD. PMID:22586125

  4. Involvement of the basolateral amygdala in muscarinic cholinergic modulation of extinction memory consolidation.

    PubMed

    Boccia, Mariano M; Blake, Mariano G; Baratti, Carlos M; McGaugh, James L

    2009-01-01

    Previous studies have reported that drugs affecting neuromodulatory systems within the basolateral amygdala (BLA), including drugs affecting muscarinic cholinergic receptors, modulate the consolidation of many kinds of training, including contextual fear conditioning (CFC). The present experiments investigated the involvement of muscarinic cholinergic influences within the BLA in modulating the consolidation of CFC extinction memory. Male Sprague Dawley rats implanted with unilateral cannula aimed at the BLA were trained on a CFC task, using footshock stimulation, and 24 and 48 h later were given extinction training by replacing them in the apparatus without footshock. Following each extinction session they received intra-BLA infusions of the cholinergic agonist oxotremorine (10 ng). Immediate post-extinction BLA infusions significantly enhanced extinction but infusions administered 180 min after extinction training did not influence extinction. Thus the oxotremorine effects were time-dependent and not attributable to non-specific effects on retention performance. These findings provide evidence that, as previously found with original CFC learning, cholinergic activation within the BLA modulates the consolidation of CFC extinction.

  5. Deep brain stimulation, histone deacetylase inhibitors and glutamatergic drugs rescue resistance to fear extinction in a genetic mouse model.

    PubMed

    Whittle, Nigel; Schmuckermair, Claudia; Gunduz Cinar, Ozge; Hauschild, Markus; Ferraguti, Francesco; Holmes, Andrew; Singewald, Nicolas

    2013-01-01

    Anxiety disorders are characterized by persistent, excessive fear. Therapeutic interventions that reverse deficits in fear extinction represent a tractable approach to treating these disorders. We previously reported that 129S1/SvImJ (S1) mice show no extinction learning following normal fear conditioning. We now demonstrate that weak fear conditioning does permit fear reduction during massed extinction training in S1 mice, but reveals specific deficiency in extinction memory consolidation/retrieval. Rescue of this impaired extinction consolidation/retrieval was achieved with d-cycloserine (N-methly-d-aspartate partial agonist) or MS-275 (histone deacetylase (HDAC) inhibitor), applied after extinction training. We next examined the ability of different drugs and non-pharmacological manipulations to rescue the extreme fear extinction deficit in S1 following normal fear conditioning with the ultimate aim to produce low fear levels in extinction retrieval tests. Results showed that deep brain stimulation (DBS) by applying high frequency stimulation to the nucleus accumbens (ventral striatum) during extinction training, indeed significantly reduced fear during extinction retrieval compared to sham stimulation controls. Rescue of both impaired extinction acquisition and deficient extinction consolidation/retrieval was achieved with prior extinction training administration of valproic acid (a GABAergic enhancer and HDAC inhibitor) or AMN082 [metabotropic glutamate receptor 7 (mGlu7) agonist], while MS-275 or PEPA (AMPA receptor potentiator) failed to affect extinction acquisition in S1 mice. Collectively, these data identify potential beneficial effects of DBS and various drug treatments, including those with HDAC inhibiting or mGlu7 agonism properties, as adjuncts to overcome treatment resistance in exposure-based therapies. This article is part of a Special Issue entitled 'Cognitive Enhancers'. PMID:22722028

  6. Deep brain stimulation, histone deacetylase inhibitors and glutamatergic drugs rescue resistance to fear extinction in a genetic mouse model

    PubMed Central

    Whittle, Nigel; Schmuckermair, Claudia; Gunduz Cinar, Ozge; Hauschild, Markus; Ferraguti, Francesco; Holmes, Andrew; Singewald, Nicolas

    2013-01-01

    Anxiety disorders are characterized by persistent, excessive fear. Therapeutic interventions that reverse deficits in fear extinction represent a tractable approach to treating these disorders. We previously reported that 129S1/SvImJ (S1) mice show no extinction learning following normal fear conditioning. We now demonstrate that weak fear conditioning does permit fear reduction during massed extinction training in S1 mice, but reveals specific deficiency in extinction memory consolidation/retrieval. Rescue of this impaired extinction consolidation/retrieval was achieved with d-cycloserine (N-methly-d-aspartate partial agonist) or MS-275 (histone deacetylase (HDAC) inhibitor), applied after extinction training. We next examined the ability of different drugs and non-pharmacological manipulations to rescue the extreme fear extinction deficit in S1 following normal fear conditioning with the ultimate aim to produce low fear levels in extinction retrieval tests. Results showed that deep brain stimulation (DBS) by applying high frequency stimulation to the nucleus accumbens (ventral striatum) during extinction training, indeed significantly reduced fear during extinction retrieval compared to sham stimulation controls. Rescue of both impaired extinction acquisition and deficient extinction consolidation/retrieval was achieved with prior extinction training administration of valproic acid (a GABAergic enhancer and HDAC inhibitor) or AMN082 [metabotropic glutamate receptor 7 (mGlu7) agonist], while MS-275 or PEPA (AMPA receptor potentiator) failed to affect extinction acquisition in S1 mice. Collectively, these data identify potential beneficial effects of DBS and various drug treatments, including those with HDAC inhibiting or mGlu7 agonism properties, as adjuncts to overcome treatment resistance in exposure-based therapies. This article is part of a Special Issue entitled ‘Cognitive Enhancers’. PMID:22722028

  7. Plasticity of Fear and Safety Neurons of the Amygdala in Response to Fear Extinction

    PubMed Central

    Sangha, Susan

    2015-01-01

    Fear inhibition learning induces plasticity and remodeling of circuits within the amygdala. Most studies examine these changes in nondiscriminative fear conditioning paradigms. Using a discriminative fear, safety, and reward conditioning task, Sangha et al. (2013) have previously reported several neural microcircuits within the basal amygdala (BA) which discriminate among these cues, including a subpopulation of neurons responding selectively to a safety cue and not a fear cue. Here, the hypothesis that these “safety” neurons isolated during discriminative conditioning are biased to become fear cue responsive as a result of extinction, when fear behavior diminishes, was tested. Although 41% of “safety” neurons became fear cue responsive as a result of extinction, the data revealed that there was no bias for these neurons to become preferentially responsive during fear extinction compared to the other identified subgroups. In addition to the plasticity seen in the “safety” neurons, 44% of neurons unresponsive to either the fear cue or safety cue during discriminative conditioning became fear cue responsive during extinction. Together these emergent responses to the fear cue as a result of extinction support the hypothesis that new learning underlies extinction. In contrast, 47% of neurons responsive to the fear cue during discriminative conditioning became unresponsive to the fear cue during extinction. These findings are consistent with a suppression of neural responding mediated by inhibitory learning, or, potentially, by direct unlearning. Together, the data support extinction as an active process involving both gains and losses of responses to the fear cue and suggests the final output of the integrated BA circuit in influencing fear behavior is a balance of excitation and inhibition, and perhaps reversal of learning-induced changes. PMID:26733838

  8. Cognitive processes during fear acquisition and extinction in animals and humans

    PubMed Central

    Hofmann, Stefan G.

    2007-01-01

    Anxiety disorders are highly prevalent. Fear conditioning and extinction learning in animals often serve as simple models of fear acquisition and exposure therapy of anxiety disorders in humans. This article reviews the empirical and theoretical literature on cognitive processes in fear acquisition, extinction, and exposure therapy. It is concluded that exposure therapy is a form of cognitive intervention that specifically changes the expectancy of harm. Implications for therapy research are discussed. PMID:17532105

  9. Different effects of low frequency stimulation to infralimbic prefrontal cortex on extinction of aversive memories.

    PubMed

    Shehadi, Kamilia; Maroun, Mouna

    2013-01-15

    Experimental extinction is a behavioral technique in which animals learn to extinguish previously learned fear responses. The infralimbic cortex (IL) of the medial prefrontal cortex has an important role in extinction of aversive memories. We have recently shown that electrical stimulation of the IL in a form of high-frequency stimulation (HFS), which induces potentiation in the IL, was associated with enhanced ability to extinguish aversive memory in two aversive paradigms, the fear conditioning and the conditioned taste aversion paradigms. These results suggest that the induction of potentiation in the IL is associated with better ability to extinguish. In the present study we examined the opposite hypothesis that inducing depression in the IL by the application of low-frequency stimulation (LFS) will result in impairments in extinction. Our results show that the application of LFS to the IL retards extinction of fear conditioning only, suggesting that the application of LFS to the IL results in impairments in extinction of conditioned fear. In the conditioned taste aversion paradigm (CTA), LFS to the IL was associated with delayed enhancement of extinction of CTA that was apparent 48 h following stimulation. These results suggest that localized electrical stimulation to the IL may be an effective method for manipulating learned fear and affecting the ability to extinguish aversive associations.

  10. Associative Accounts of Recovery-from-Extinction Effects

    PubMed Central

    McConnell, Bridget L.; Miller, Ralph R.

    2014-01-01

    Recovery-from-extinction effects (e.g., spontaneous recovery, renewal, reinstatement, and facilitated reacquisition) have become the focus of much research in recent years. However, despite a great deal of empirical data, there are few theoretical explanations for these effects. This paucity poses a severe limitation on our understanding of these behavioral effects, impedes advances in uncovering neural mechanisms of response recovery, and reduces our potential to prevent relapse after exposure therapy. Towards correcting this oversight, this review takes prominent models of associative learning that have been used in the past and continue to be used today to explain Pavlovian conditioning and extinction, and assesses how each model can be applied to account for recovery-from-extinction effects. The models include the Rescorla-Wagner (1972) model, Mackintosh's (1975) attentional model, Pearce and Hall's (1980) attentional model, Wagner's (1981) SOP model, Pearce's (1987) configural model, McLaren and Mackintosh's (2002) elemental model, and Stout and Miller's (2007) SOCR (comparator hypothesis) model. Each model is assessed for how well it explains or does not explain the various recovery-from-extinction phenomena. We offer some suggestions for how the models might be modified to account for these effects in those instances in which they initially fail. PMID:24707062

  11. Darwin and the uses of extinction.

    PubMed

    Beer, Gillian

    2009-01-01

    We currently view extinction with dismay and even horror, but Darwin saw extinction as ordinary and as necessary to evolutionary change. Still, the degree to which extinction is fundamental to his theory is rarely discussed. This essay examines Darwin's linking of the idea of "improvement" with that of natural selection and tracks a cluster of reasons for our changed valuation of extinction now. Those reasons demonstrate how scientific information and ideological preferences have reshaped the concept. The essay challenges the reader to assess some current assumptions about extinction and concludes by considering the shift in Darwin's own understanding from the "Origin" to the late "Autobiography".

  12. Darwin and the uses of extinction.

    PubMed

    Beer, Gillian

    2009-01-01

    We currently view extinction with dismay and even horror, but Darwin saw extinction as ordinary and as necessary to evolutionary change. Still, the degree to which extinction is fundamental to his theory is rarely discussed. This essay examines Darwin's linking of the idea of "improvement" with that of natural selection and tracks a cluster of reasons for our changed valuation of extinction now. Those reasons demonstrate how scientific information and ideological preferences have reshaped the concept. The essay challenges the reader to assess some current assumptions about extinction and concludes by considering the shift in Darwin's own understanding from the "Origin" to the late "Autobiography". PMID:19824221

  13. The extinction differential induced virulence macroevolution

    NASA Astrophysics Data System (ADS)

    Zhang, Feng; Xu, Liufang; Wang, Jin

    2014-04-01

    We apply the potential-flux landscape theory to deal with the large fluctuation induced extinction phenomena. We quantify the most probable extinction pathway on the landscape and measure the extinction risk by the landscape topography. In this Letter, we investigate the disease extinction through an epidemic model described by a set of chemical reaction. We found the virulence-differential-dependent symbioses between mother and daughter pathogen species: mutualism and parasitism. The symbioses, whether mutualism or parasitism, benefit the higher virulence species. This implies that speciation towards lower virulence is an effective strategy for a pathogen species to reduce its extinction risk.

  14. The peculiar extinction of Herschel 36

    NASA Technical Reports Server (NTRS)

    Donn, B.; Hecht, J. H.; Helfer, H. L.; Wolf, J.; Pipher, J. L.

    1982-01-01

    The extinction of Herschel 36 was measured and found to be peculiar in the same sense as that observed in Orion. Following the treatment of Mathis and Wallenhorst, this can be explained by the presence of large silicate and graphite grains than are normally found in the interstellar medium. Correcting the stellar flux for foreground extinction results in a residual extinction curve for the associated dust cloud, with an unusually small normalized extinction (less than 1.0) at 1500 A. This low UV extinction may be due to the effects of scattering by the dust cloud material.

  15. Environmental trends in extinction during the Paleozoic

    NASA Technical Reports Server (NTRS)

    Sepkoski, J. John, Jr.

    1987-01-01

    Extinction intensities calculated from 505 Paleozoic marine assemblages divided among six environmental zones and 40 stratigraphic intervals indicate that whole communities exhibit increasing extinction offshore but that genera within individual taxonomic classes tend to have their highest extinction onshore. The offshore trend at the community level results from a concentration of genera in classes with low characteristic extinction rates in nearshore environments. This finding is consistent with the ecologic expectation that organisms inhabiting unpredictably fluctuating environments should suffer more extinction than counterparts living under more predictably equitable conditions.

  16. Surviving mass extinction by bridging the benthic/planktic divide

    PubMed Central

    Darling, Kate F.; Thomas, Ellen; Kasemann, Simone A.; Seears, Heidi A.; Smart, Christopher W.; Wade, Christopher M.

    2009-01-01

    Evolution of planktic organisms from benthic ancestors is commonly thought to represent unidirectional expansion into new ecological domains, possibly only once per clade. For foraminifera, this evolutionary expansion occurred in the Early–Middle Jurassic, and all living and extinct planktic foraminifera have been placed within 1 clade, the Suborder Globigerinina. The subsequent radiation of planktic foraminifera in the Jurassic and Cretaceous resulted in highly diverse assemblages, which suffered mass extinction at the end of the Cretaceous, leaving an impoverished assemblage dominated by microperforate triserial and biserial forms. The few survivor species radiated to form diverse assemblages once again in the Cenozoic. There have, however, long been doubts regarding the monophyletic origin of planktic foraminifera. We present surprising but conclusive genetic evidence that the Recent biserial planktic Streptochilus globigerus belongs to the same biological species as the benthic Bolivina variabilis, and geochemical evidence that this ecologically flexible species actively grows within the open-ocean surface waters, thus occupying both planktic and benthic domains. Such a lifestyle (tychopelagic) had not been recognized as adapted by foraminifera. Tychopelagic are endowed with great ecological advantage, enabling rapid recolonization of the extinction-susceptible pelagic domain from the benthos. We argue that the existence of such forms must be considered in resolving foraminiferal phylogeny. PMID:19574452

  17. Inhibiting corticosterone synthesis during fear memory formation exacerbates cued fear extinction memory deficits within the single prolonged stress model.

    PubMed

    Keller, Samantha M; Schreiber, William B; Stanfield, Briana R; Knox, Dayan

    2015-01-01

    Using the single prolonged stress (SPS) animal model of post-traumatic stress disorder (PTSD), previous studies suggest that enhanced glucocorticoid receptor (GR) expression leads to cued fear extinction retention deficits. However, it is unknown how the endogenous ligand of GRs, corticosterone (CORT), may contribute to extinction retention deficits in the SPS model. Given that CORT synthesis during fear learning is critical for fear memory consolidation and SPS enhances GR expression, CORT synthesis during fear memory formation could strengthen fear memory in SPS rats by enhancing GR activation during fear learning. In turn, this could lead to cued fear extinction retention deficits. We tested the hypothesis that CORT synthesis during fear learning leads to cued fear extinction retention deficits in SPS rats by administering the CORT synthesis inhibitor metyrapone to SPS and control rats prior to fear conditioning, and observed the effect this had on extinction memory. Inhibiting CORT synthesis during fear memory formation in control rats tended to decrease cued freezing, though this effect never reached statistical significance. Contrary to our hypothesis, inhibiting CORT synthesis during fear memory formation disrupted extinction retention in SPS rats. This finding suggests that even though SPS exposure leads to cued fear extinction memory deficits, CORT synthesis during fear memory formation enhances extinction retention in SPS rats. This suggests that stress-induced CORT synthesis in previously stressed rats can be beneficial.

  18. Using holography to measure extinction.

    PubMed

    Berg, Matthew J; Subedi, Nava R; Anderson, Peter A; Fowler, Nicholas B

    2014-07-01

    This work presents a new concept to measure the extinction cross section for a single particle in situ. The concept involves recording the hologram produced by the interference of a particle's forward-scattered light with the incident light. This interference pattern is fundamentally connected to the energy flow that gives rise to extinction, and, by integrating this measured pattern, one obtains an approximation for the cross section. Mie theory is used to show that this approximation can be as little as 1% in error of the true value for many cases of practical interest. Moreover, since an image of the particle can be computationally reconstructed from a measured hologram using the Fresnel-Kirchhoff diffraction theory, one can obtain the cross section simultaneously with the particle shape and size.

  19. Neanderthal Extinction by Competitive Exclusion

    PubMed Central

    Banks, William E.; d'Errico, Francesco; Peterson, A. Townsend; Kageyama, Masa; Sima, Adriana; Sánchez-Goñi, Maria-Fernanda

    2008-01-01

    Background Despite a long history of investigation, considerable debate revolves around whether Neanderthals became extinct because of climate change or competition with anatomically modern humans (AMH). Methodology/Principal Findings We apply a new methodology integrating archaeological and chronological data with high-resolution paleoclimatic simulations to define eco-cultural niches associated with Neanderthal and AMH adaptive systems during alternating cold and mild phases of Marine Isotope Stage 3. Our results indicate that Neanderthals and AMH exploited similar niches, and may have continued to do so in the absence of contact. Conclusions/Significance The southerly contraction of Neanderthal range in southwestern Europe during Greenland Interstadial 8 was not due to climate change or a change in adaptation, but rather concurrent AMH geographic expansion appears to have produced competition that led to Neanderthal extinction. PMID:19107186

  20. A review of extinction in experimental populations.

    PubMed

    Griffen, Blaine D; Drake, John M

    2008-11-01

    1. Population extinction is a fundamental ecological process. Recent experimental work has begun to test the large body of theory that predicts how demographic, genetic and environmental factors influence extinction risk. We review empirical studies of extinction conducted under controlled laboratory conditions. Our synthesis highlights four findings. First, extinction theory largely considers individual, isolated populations. However, species interactions frequently altered or even reversed the influence of environmental factors on population extinction as compared to single-species conditions, highlighting the need to integrate community ecology into population theory. 2. While most single-species studies qualitatively agree with theoretical predictions, studies are needed that quantitatively compare observed and predicted extinction rates. A quantitative understanding of extinction processes is needed to further advance theory and to predict population extinction resulting from human activities. 3. Many stresses leading to population extinction can be assuaged by migration between subpopulations. However, too much migration increases synchrony between subpopulations and thus increases extinction risk. Research is needed to determine how to strike a balance that maximizes the benefit of migration. 4. Results from laboratory experiments often conflict with field studies. Understanding these inconsistencies is crucial for extending extinction theory to natural populations.

  1. Optimising Extinction of Conditioned Disgust

    PubMed Central

    Bosman, Renske C.; Borg, Charmaine; de Jong, Peter J.

    2016-01-01

    Maladaptive disgust responses are tenacious and resistant to exposure-based interventions. In a similar vein, laboratory studies have shown that conditioned disgust is relatively insensitive to Conditioned Stimulus (CS)-only extinction procedures. The relatively strong resistance to extinction might be explained by disgust’s adaptive function to motivate avoidance from contamination threats (pathogens) that cannot be readily detected and are invisible to the naked eye. Therefore, the mere visual presentation of unreinforced disgust eliciting stimuli might not be sufficient to correct a previously acquired threat value of the CS+. Following this, the current study tested whether the efficacy of CS-only exposure can be improved by providing additional safety information about the CS+. For the CSs we included two neutral items a pea soup and a sausage roll, whereas for the Unconditioned Stimulus (US) we used one video clip of a woman vomiting and a neutral one about glass blowing. The additional safety information was conveyed by allowing actual contact with the CS+ or by observing an actress eating the food items representing the CS+. When additional safety information was provided via allowing direct contact with the CS+, there was a relatively strong post-extinction increase in participants’ willingness-to-eat the CS+. This beneficial effect was still evident at one-week follow up. Also self-reported disgust was lower at one-week follow up when additional safety information was provided. The current findings help explain why disgust is relatively insensitive to CS-only extinction procedures, and provide helpful starting points to improve interventions that are aimed to reduce distress in disgust-related psychopathology. PMID:26849211

  2. Optimising Extinction of Conditioned Disgust.

    PubMed

    Bosman, Renske C; Borg, Charmaine; de Jong, Peter J

    2016-01-01

    Maladaptive disgust responses are tenacious and resistant to exposure-based interventions. In a similar vein, laboratory studies have shown that conditioned disgust is relatively insensitive to Conditioned Stimulus (CS)-only extinction procedures. The relatively strong resistance to extinction might be explained by disgust's adaptive function to motivate avoidance from contamination threats (pathogens) that cannot be readily detected and are invisible to the naked eye. Therefore, the mere visual presentation of unreinforced disgust eliciting stimuli might not be sufficient to correct a previously acquired threat value of the CS+. Following this, the current study tested whether the efficacy of CS-only exposure can be improved by providing additional safety information about the CS+. For the CSs we included two neutral items a pea soup and a sausage roll, whereas for the Unconditioned Stimulus (US) we used one video clip of a woman vomiting and a neutral one about glass blowing. The additional safety information was conveyed by allowing actual contact with the CS+ or by observing an actress eating the food items representing the CS+. When additional safety information was provided via allowing direct contact with the CS+, there was a relatively strong post-extinction increase in participants' willingness-to-eat the CS+. This beneficial effect was still evident at one-week follow up. Also self-reported disgust was lower at one-week follow up when additional safety information was provided. The current findings help explain why disgust is relatively insensitive to CS-only extinction procedures, and provide helpful starting points to improve interventions that are aimed to reduce distress in disgust-related psychopathology. PMID:26849211

  3. CO2 and the end-Triassic mass extinction.

    PubMed

    Beerling, David

    2002-01-24

    The end of the Triassic period was marked by one of the largest and most enigmatic mass-extinction events in Earth's history and, with few reliable marine geochemical records, terrestrial sediments offer an important means of deciphering environmental changes at this time. Tanner et al. describe an isotopic study of Mesozoic fossil soils which suggests that the atmospheric concentration of carbon dioxide (pCO2) across the Triassic-Jurassic boundary was relatively constant (within 250 p.p.m.v.), but this is inconsistent with high-resolution evidence from the stomatal characters of fossil leaves. Here I show that the temporal resolution of the fossil-soil samples may have been inadequate for detecting a transient rise in pCO2. I also show that the fossil-soil data are consistent with a large increase in pCO2 across the Triassic-Jurassic boundary when variations in the stable carbon isotope (denoted as delta13C) in terrestrial plant leaves are taken into account. These factors suggest that the linkage between pCO2, global warming and the end-Triassic mass extinction remains intact. PMID:11807542

  4. CO2 and the end-Triassic mass extinction.

    PubMed

    Beerling, David

    2002-01-24

    The end of the Triassic period was marked by one of the largest and most enigmatic mass-extinction events in Earth's history and, with few reliable marine geochemical records, terrestrial sediments offer an important means of deciphering environmental changes at this time. Tanner et al. describe an isotopic study of Mesozoic fossil soils which suggests that the atmospheric concentration of carbon dioxide (pCO2) across the Triassic-Jurassic boundary was relatively constant (within 250 p.p.m.v.), but this is inconsistent with high-resolution evidence from the stomatal characters of fossil leaves. Here I show that the temporal resolution of the fossil-soil samples may have been inadequate for detecting a transient rise in pCO2. I also show that the fossil-soil data are consistent with a large increase in pCO2 across the Triassic-Jurassic boundary when variations in the stable carbon isotope (denoted as delta13C) in terrestrial plant leaves are taken into account. These factors suggest that the linkage between pCO2, global warming and the end-Triassic mass extinction remains intact.

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

    PubMed

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

    2016-07-01

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

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

    PubMed

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

    2016-07-01

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

  7. Converging towards the optimal path to extinction

    PubMed Central

    Schwartz, Ira B.; Forgoston, Eric; Bianco, Simone; Shaw, Leah B.

    2011-01-01

    Extinction appears ubiquitously in many fields, including chemical reactions, population biology, evolution and epidemiology. Even though extinction as a random process is a rare event, its occurrence is observed in large finite populations. Extinction occurs when fluctuations owing to random transitions act as an effective force that drives one or more components or species to vanish. Although there are many random paths to an extinct state, there is an optimal path that maximizes the probability to extinction. In this paper, we show that the optimal path is associated with the dynamical systems idea of having maximum sensitive dependence to initial conditions. Using the equivalence between the sensitive dependence and the path to extinction, we show that the dynamical systems picture of extinction evolves naturally towards the optimal path in several stochastic models of epidemics. PMID:21571943

  8. Were all extinction events caused by impacts?

    NASA Technical Reports Server (NTRS)

    Sheehan, P. M.; Coorough, P. J.

    1994-01-01

    Extraterrestrial impacts are firmly implicated in several of the five major Phanerozoic extinction events. A critical issue now is whether extraterrestrial events have been the only mechanism that produced physical changes of sufficient magnitude to cause major extinction events. While we believe the evidence is overwhelming that the KT extinction event was caused by an impact, we also find that an event of similar or larger size near the end of the Ordovician is best explained by terrestrial causes. The Ordovician extinction event (End-O extinction event) occurred near the end of the Ordovician, but the interval of extinction was completed prior to the newly established Ordovician-Silurian boundary. In spite of extensive field studies, a convincing signature of an associated impact has not been found. However, a prominent glaciation does coincide with the End-O extinction event.

  9. The Case for Extraterrestrial Causes of Extinction

    NASA Astrophysics Data System (ADS)

    Raup, D. M.

    1989-11-01

    The dramatic increase in our knowledge of large-body impacts that have occurred in Earth's history has led to strong arguments for the plausibility of meteorite impact as a cause of extinction. Proof of causation is often hampered, however, by our inability to demonstrate the synchronism of specific impacts and extinctions. A central problem is range truncation: the last reported occurrences of fossil taxa generally underestimate the true times of extinction. Range truncation, because of gaps in sedimentation, lack of preservation, or lack of discovery, can make sudden extinctions appear gradual and gradual extinctions appear sudden. Also, stepwise extinction may appear as an artefact of range truncation. These effects are demonstrated by experiments performed on data from field collections of Cretaceous ammonities from Zumaya (Spain). The challenge for future research is to develop a new calculus for treating biostratigraphic data so that fossils can provide more accurate assessments of the timing of extinctions.

  10. Phylogenetic conservatism of extinctions in marine bivalves.

    PubMed

    Roy, Kaustuv; Hunt, Gene; Jablonski, David

    2009-08-01

    Evolutionary histories of species and lineages can influence their vulnerabilities to extinction, but the importance of this effect remains poorly explored for extinctions in the geologic past. When analyzed using a standardized taxonomy within a phylogenetic framework, extinction rates of marine bivalves estimated from the fossil record for the last approximately 200 million years show conservatism at multiple levels of evolutionary divergence, both within individual families and among related families. The strength of such phylogenetic clustering varies over time and is influenced by earlier extinction history, especially by the demise of volatile taxa in the end-Cretaceous mass extinction. Analyses of the evolutionary roles of ancient extinctions and predictive models of vulnerability of taxa to future natural and anthropogenic stressors should take phylogenetic relationships and extinction history into account.

  11. Falling for Clay Leaves.

    ERIC Educational Resources Information Center

    Kernan, Christine

    2002-01-01

    Describes an art project that integrated science and art education. Explains that students create ceramic bowls by using real leaves. Discusses the process of creating the ceramic bowls, including how to glaze the bowls. Includes a list of materials. (CMK)

  12. A comparison of the short- and long-term effects of corticosterone exposure on extinction in adolescence versus adulthood.

    PubMed

    Den, Miriam Liora; Altmann, Sarah R; Richardson, Rick

    2014-12-01

    Human and nonhuman adolescents have impaired retention of extinction of learned fear, relative to juveniles and adults. It is unknown whether exposure to stress affects extinction differently in adolescents versus adults. These experiments compared the short- and long-term effects of exposure to the stress-related hormone corticosterone (CORT) on the extinction of learned fear in adolescent and adult rats. Across all experiments, adolescent and adult rats were trained to exhibit good extinction retention by giving extinction training across 2 consecutive days. Despite this extra training, adolescents exposed to 1 week of CORT (200 μg/ml) in their drinking water showed impaired extinction retention when trained shortly after the CORT was removed (Experiment 1a). In contrast, adult rats exposed to CORT (200 μg/ml) for the same duration did not exhibit deficits in extinction retention (Experiment 1b). Exposing adolescents to half the amount of CORT (100 μg/ml; Experiment 1c) for 1 week similarly disrupted extinction retention. Extinction impairments in adult rats were only observed after 3 weeks, rather than 1 week, of CORT (200 μg/ml; Experiment 1d). Remarkably, however, adult rats showed impaired extinction retention if they had been exposed to 1 week of CORT (200 μg/ml) during adolescence (Experiment 2). Finally, exposure to 3 weeks of CORT (200 μg/ml) in adulthood led to long-lasting extinction deficits after a 6-week drug-free period (Experiment 3). These findings suggest that although CORT disrupts both short- and long-term extinction retention in adolescents and adults, adolescents may be more vulnerable to these effects because of the maturation of stress-sensitive brain regions. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

  13. Lack of renewal effect in extinction of naturally acquired conditioned eyeblink responses, but possible dependency on physical context.

    PubMed

    Claassen, J; Mazilescu, L; Thieme, A; Bracha, V; Timmann, D

    2016-01-01

    Context dependency of extinction is well known and has extensively been studied in fear conditioning, but has rarely been assessed in eyeblink conditioning. One way to demonstrate context dependency of extinction is the renewal effect. ABA paradigms are most commonly used to show the renewal effect of extinguished learned fear: if acquisition takes place in context A, and extinction takes place in context B (extinction phase), learned responses will recover in subsequent extinction trials presented in context A (renewal phase). The renewal effect of the visual threat eyeblink response (VTER), a conditioned eyeblink response, which is naturally acquired in early infancy, was examined in a total of 48 young and healthy participants with two experiments using an ABA paradigm. Twenty paired trials were performed in context A (baseline trials), followed by 50 extinction trials in context B (extinction phase) and 50 extinction trials in context A (renewal phase). In 24 participants, contexts A and B were two different rooms, and in the other 24 participants, two different background colors (orange and blue) and noises were used. To rule out spontaneous recovery, an AAA design was used for comparison. There were significant effects of extinction in both experiments. No significant renewal effects were observed. In experiment 2, however, extinction was significantly less using orange background during extinction compared to the blue background. The present findings suggest that extinction of conditioned eyeblinks depends on the physical context. Findings add to the animal literature that context can play a role in the acquisition of classically conditioned eyeblink responses. Future studies, however, need to be performed to confirm the present findings. Lack of renewal effect may be explained by the highly overlearned character of the VTER.

  14. Effects of rapid eye movement sleep deprivation on fear extinction recall and prediction error signaling.

    PubMed

    Spoormaker, Victor I; Schröter, Manuel S; Andrade, Kátia C; Dresler, Martin; Kiem, Sara A; Goya-Maldonado, Roberto; Wetter, Thomas C; Holsboer, Florian; Sämann, Philipp G; Czisch, Michael

    2012-10-01

    In a temporal difference learning approach of classical conditioning, a theoretical error signal shifts from outcome deliverance to the onset of the conditioned stimulus. Omission of an expected outcome results in a negative prediction error signal, which is the initial step towards successful extinction and may therefore be relevant for fear extinction recall. As studies in rodents have observed a bidirectional relationship between fear extinction and rapid eye movement (REM) sleep, we aimed to test the hypothesis that REM sleep deprivation impairs recall of fear extinction through prediction error signaling in humans. In a three-day design with polysomnographically controlled REM sleep deprivation, 18 young, healthy subjects performed a fear conditioning, extinction and recall of extinction task with visual stimuli, and mild electrical shocks during combined functional magnetic resonance imaging (fMRI) and skin conductance response (SCR) measurements. Compared to the control group, the REM sleep deprivation group had increased SCR scores to a previously extinguished stimulus at early recall of extinction trials, which was associated with an altered fMRI time-course in the left middle temporal gyrus. Post-hoc contrasts corrected for measures of NREM sleep variability also revealed between-group differences primarily in the temporal lobe. Our results demonstrate altered prediction error signaling during recall of fear extinction after REM sleep deprivation, which may further our understanding of anxiety disorders in which disturbed sleep and impaired fear extinction learning coincide. Moreover, our findings are indicative of REM sleep related plasticity in regions that also show an increase in activity during REM sleep.

  15. Learning.

    ERIC Educational Resources Information Center

    Glaser, Robert

    A report on learning psychology and its relationship to the study of school learning emphasizes the increasing interaction between theorists and educational practitioners, particularly in attempting to learn which variables influence the instructional process and to find an appropriate methodology to measure and evaluate learning. "Learning…

  16. Retrieval of memory for fear-motivated training initiates extinction requiring protein synthesis in the rat hippocampus.

    PubMed

    Vianna, M R; Szapiro, G; McGaugh, J L; Medina, J H; Izquierdo, I

    2001-10-01

    Evidence that protein synthesis inhibitors induce amnesia in a variety of species and learning paradigms indicates that the consolidation of newly acquired information into stable memories requires the synthesis of new proteins. Because extinction of a response also requires acquisition of new information, extinction, like original learning, would be expected to require protein synthesis. The present experiments examined the involvement of protein synthesis in the hippocampus in the extinction of a learned fear-based response known to involve the hippocampus. Rats were trained in a one-trial inhibitory avoidance task in which they received footshock after stepping from a small platform to a grid floor. They were then given daily retention tests without footshock. The inhibitory response (e.g., remaining on the platform) gradually extinguished with repeated testing over several days. Footshock administered in a different context, instead of a retention test, prevented the extinction. Infusions of the protein synthesis inhibitor anisomycin (80 microg) into the CA1 region of the hippocampus (bilaterally) 10 min before inhibitory avoidance training impaired retention on all subsequent tests. Anisomycin infused into the hippocampus immediately after the 1st retention test blocked extinction of the response. Infusions administered before the 1st retention test induced a temporary (i.e., 1 day) reduction in retention performance and blocked subsequent extinction. These findings are consistent with other evidence that anisomycin blocks both the consolidation of original learning and extinction.

  17. Looking beyond fear: the extinction of other emotions implicated in anxiety disorders.

    PubMed

    Mason, Elizabeth C; Richardson, Rick

    2010-01-01

    Previous research examining anxiety has traditionally focused on models of fear. More recently, attention has been directed to the role of disgust as an important emotion in the context of certain anxiety disorders. Further, it has been suggested that disgust, a form of evaluative responding, may be resistant to extinction and may contribute to relapse. However, previous work on this has largely relied on self-report ratings. In the current experiment, using a disgust conditioning and extinction procedure, disgust reactions were indeed shown to be resistant to extinction, as indexed by both self-report and an objective behavioral measure (visual avoidance). Furthermore, our research shows that individuals with greater levels of disgust sensitivity exhibit heightened resistance to extinction. In addition, expectancy of the disgusting US during extinction was dissociated from measures of disgust responding. Given that the treatment of choice for anxiety disorders (exposure therapy) is based on models of extinction, this research suggests that current treatments for anxiety disorders may not be adequately targeting disgust reactions, a crucial maintaining factor in certain anxiety disorders. As such, this inattention to disgust reactions may reduce the effectiveness of treatment in the short-term or may leave the patient vulnerable to relapse in the long-term.

  18. Extinction of fear-potentiated startle: blockade by infusion of an NMDA antagonist into the amygdala.

    PubMed

    Falls, W A; Miserendino, M J; Davis, M

    1992-03-01

    Data derived from in vitro preparations indicate that NMDA receptors play a critical role in synaptic plasticity in the CNS. More recently, in vivo pharmacological manipulations have suggested that an NMDA-dependent process may be involved in specific forms of behavioral plasticity. All of the work thus far has focused on the possible role of NMDA receptors in the acquisition of responses. However, there are many examples in the behavioral literature of learning-induced changes that involve the reduction or elimination of a previously acquired response. Experimental extinction is a primary example of the elimination of a learned response. Experimental extinction is well described in the behavioral literature, but has not received the same attention in the neurobiological literature. As a result, the neural mechanisms that underlie this important form of learning are not at all understood. In the present experiments, the fear-potentiated startle paradigm was employed to begin to investigate neural mechanisms of extinction. The results show that infusion of the NMDA antagonist D,L-2-amino-5-phosphonovaleric acid (AP5) into the amygdala, a limbic structure known to be important for fear conditioning, dose-dependently blocked extinction of conditioned fear. Control experiments showed that the blockade of extinction was neither the result of the permanent disruption of amygdaloid function nor the result of decreased sensitivity of the animals to the conditioned stimulus. Infusion of AP5 into the interpositus nucleus of the cerebellum, a control site, did not block extinction. Finally, intra-amygdala infusion of a selected dose of the non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione did not block extinction of conditioned fear. These results, together with a previous report from our laboratory (Miserendino et al., 1990), demonstrate the importance of the amygdala in the elaboration of conditioned fear and suggest that an NMDA-dependent process might underlie the

  19. Extinction, reacquisition, and rapid forgetting of eyeblink conditioning in developing rats

    PubMed Central

    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 Experiment 1, post-natal day (P) 17 and 24 rats were trained to a criterion of 80% conditioned responses (CRs) using stimulation of the middle cerebellar peduncle (MCP) as a conditioned stimulus (CS). Stimulation CS-alone extinction training commenced 24 h later, followed by reacquisition training after the fourth extinction session. Contrary to expected results, rats trained starting on P17 showed significantly fewer CRs to stimulation CS-alone presentations relative to P24s, including fewer CRs as early as the first block of extinction session 1. Furthermore, the P17 group was slower to reacquire following extinction. Experiment 2 was run to determine the extent to which the low CR percentage observed in P17s early in extinction reflected rapid forgetting versus rapid extinction. Twenty-four hours after reaching criterion, subjects were trained in a session split into 50 stimulation CS-unconditioned stimulus paired trials followed immediately by 50 stimulation CS-alone trials. With this “immediate” extinction protocol, CR percentages during the first block of stimulation CS-alone presentations were equivalent to terminal acquisition levels at both ages but extinction was more rapid in the P17 group. These findings indicate that forgetting is observed in P17 relative to P24 rats 24 h following acquisition. The forgetting in P17 rats has important implications for the neurobiological mechanisms of memory in the developing cerebellum. PMID:25403458

  20. Revisiting propranolol and PTSD: Memory erasure or extinction enhancement?

    PubMed

    Giustino, Thomas F; Fitzgerald, Paul J; Maren, Stephen

    2016-04-01

    Posttraumatic stress disorder (PTSD) has been described as the only neuropsychiatric disorder with a known cause, yet effective behavioral and pharmacotherapies remain elusive for many afflicted individuals. PTSD is characterized by heightened noradrenergic signaling, as well as a resistance to extinction learning. Research aimed at promoting more effective treatment of PTSD has focused on memory erasure (disrupting reconsolidation) and/or enhancing extinction retention through pharmacological manipulations. Propranolol, a β-adrenoceptor antagonist, has received considerable attention for its therapeutic potential in PTSD, although its impact on patients is not always effective. In this review, we briefly examine the consequences of β-noradrenergic manipulations on both reconsolidation and extinction learning in rodents and in humans. We suggest that propranolol is effective as a fear-reducing agent when paired with behavioral therapy soon after trauma when psychological stress is high, possibly preventing or dampening the later development of PTSD. In individuals who have already suffered from PTSD for a significant period of time, propranolol may be less effective at disrupting reconsolidation of strong fear memories. Also, when PTSD has already developed, chronic treatment with propranolol may be more effective than acute intervention, given that individuals with PTSD tend to experience long-term, elevated noradrenergic hyperarousal.

  1. Estradiol accelerates extinction of lithium chloride-induced conditioned taste aversions through its illness-associated properties.

    PubMed

    Yuan, D L; Chambers, K C

    1999-12-01

    Estradiol accelerates extinction of LiCl-induced conditioned taste aversions when it is present during a period that starts 2-3 days after acquisition and extends throughout extinction (before and during extinction). It has been suggested that estradiol acts before, not during, extinction and that its effect on extinction is associated with its illness-inducing properties. This hypothesis is based on previous work which shows an attenuation of conditioned taste aversion learning when rats are exposed to illness-inducing agents during a period that starts 2 days after acquisition and ends 2 days before extinction trials are initiated. Four experiments were designed to test elements of this hypothesis. The first two experiments demonstrated that if an estradiol-filled Silastic capsule is implanted before extinction of a LiCl-induced aversion, when the conditioned taste is not present, it accelerates extinction, but if it is implanted during extinction, when the conditioned taste is present, it prolongs extinction. The third experiment showed that the same dose of estradiol that accelerates extinction of a LiCl-induced aversion was effective in producing a conditioned taste aversion when it was present for 18 h after consumption of a novel sucrose solution. The fourth experiment indicated that serum levels of estradiol were elevated during the 18 h. These results are consistent with the hypothesis that the acceleration of extinction by estradiol is associated with its illness-inducing properties. It is suggested that estradiol acts on neural areas that mediate illness information and that one of these areas, the area postrema is necessary for estradiol to accelerate extinction of a LiCl-induced aversion.

  2. The role of extinction in evolution.

    PubMed Central

    Raup, D M

    1994-01-01

    The extinction of species is not normally considered an important element of neodarwinian theory, in contrast to the opposite phenomenon, speciation. This is surprising in view of the special importance Darwin attached to extinction, and because the number of species extinctions in the history of life is almost the same as the number of originations; present-day biodiversity is the result of a trivial surplus of originations, cumulated over millions of years. For an evolutionary biologist to ignore extinction is probably as foolhardy as for a demographer to ignore mortality. The past decade has seen a resurgence of interest in extinction, yet research on the topic is still at a reconnaissance level, and our present understanding of its role in evolution is weak. Despite uncertainties, extinction probably contains three important elements. (i) For geographically widespread species, extinction is likely only if the killing stress is one so rare as to be beyond the experience of the species, and thus outside the reach of natural selection. (ii) The largest mass extinctions produce major restructuring of the biosphere wherein some successful groups are eliminated, allowing previously minor groups to expand and diversify. (iii) Except for a few cases, there is little evidence that extinction is selective in the positive sense argued by Darwin. It has generally been impossible to predict, before the fact, which species will be victims of an extinction event. PMID:8041694

  3. The role of extinction in evolution

    NASA Technical Reports Server (NTRS)

    Raup, D. M.

    1994-01-01

    The extinction of species is not normally considered an important element of neodarwinian theory, in contrast to the opposite phenomenon, speciation. This is surprising in view of the special importance Darwin attached to extinction, and because the number of species extinctions in the history of life is almost the same as the number of originations; present-day biodiversity is the result of a trivial surplus of originations, cumulated over millions of years. For an evolutionary biologist to ignore extinction is probably as foolhardy as for a demographer to ignore mortality. The past decade has seen a resurgence of interest in extinction, yet research on the topic is still at a reconnaissance level, and our present understanding of its role in evolution is weak. Despite uncertainties, extinction probably contains three important elements. (i) For geographically widespread species, extinction is likely only if the killing stress is one so rare as to be beyond the experience of the species, and thus outside the reach of natural selection. (ii) The largest mass extinctions produce major restructuring of the biosphere wherein some successful groups are eliminated, allowing previously minor groups to expand and diversify. (iii) Except for a few cases, there is little evidence that extinction is selective in the positive sense argued by Darwin. It has generally been impossible to predict, before the fact, which species will be victims of an extinction event.

  4. The ethics of reviving long extinct species.

    PubMed

    Sandler, Ronald

    2014-04-01

    There now appears to be a plausible pathway for reviving species that have been extinct for several decades, centuries, or even millennia. I conducted an ethical analysis of de-extinction of long extinct species. I assessed several possible ethical considerations in favor of pursuing de-extinction: that it is a matter of justice; that it would reestablish lost value; that it would create new value; and that society needs it as a conservation last resort. I also assessed several possible ethical arguments against pursuing de-extinction: that it is unnatural; that it could cause animal suffering; that it could be ecologically problematic or detrimental to human health; and that it is hubristic. There are reasons in favor of reviving long extinct species, and it can be ethically acceptable to do so. However, the reasons in favor of pursuing de-extinction do not have to do with its usefulness in species conservation; rather, they concern the status of revived species as scientific and technological achievements, and it would be ethically problematic to promote de-extinction as a significant conservation strategy, because it does not prevent species extinctions, does not address the causes of extinction, and could be detrimental to some species conservation efforts. Moreover, humanity does not have a responsibility or obligation to pursue de-extinction of long extinct species, and reviving them does not address any urgent problem. Therefore, legitimate ecological, political, animal welfare, legal, or human health concerns associated with a de-extinction (and reintroduction) must be thoroughly addressed for it to be ethically acceptable.

  5. The ethics of reviving long extinct species.

    PubMed

    Sandler, Ronald

    2014-04-01

    There now appears to be a plausible pathway for reviving species that have been extinct for several decades, centuries, or even millennia. I conducted an ethical analysis of de-extinction of long extinct species. I assessed several possible ethical considerations in favor of pursuing de-extinction: that it is a matter of justice; that it would reestablish lost value; that it would create new value; and that society needs it as a conservation last resort. I also assessed several possible ethical arguments against pursuing de-extinction: that it is unnatural; that it could cause animal suffering; that it could be ecologically problematic or detrimental to human health; and that it is hubristic. There are reasons in favor of reviving long extinct species, and it can be ethically acceptable to do so. However, the reasons in favor of pursuing de-extinction do not have to do with its usefulness in species conservation; rather, they concern the status of revived species as scientific and technological achievements, and it would be ethically problematic to promote de-extinction as a significant conservation strategy, because it does not prevent species extinctions, does not address the causes of extinction, and could be detrimental to some species conservation efforts. Moreover, humanity does not have a responsibility or obligation to pursue de-extinction of long extinct species, and reviving them does not address any urgent problem. Therefore, legitimate ecological, political, animal welfare, legal, or human health concerns associated with a de-extinction (and reintroduction) must be thoroughly addressed for it to be ethically acceptable. PMID:24372907

  6. Spatial memory extinction differentially affects dorsal and ventral hippocampal metabolic activity and associated functional brain networks.

    PubMed

    Méndez-Couz, Marta; González-Pardo, Héctor; Vallejo, Guillermo; Arias, Jorge L; Conejo, Nélida M

    2016-10-01

    Previous studies showed the involvement of brain regions associated with both spatial learning and associative learning in spatial memory extinction, although the specific role of the dorsal and ventral hippocampus and the extended hippocampal system including the mammillary body in the process is still controversial. The present study aimed to identify the involvement of the dorsal and ventral hippocampus, together with cortical regions, the amygdaloid nuclei, and the mammillary bodies in the extinction of a spatial memory task. To address these issues, quantitative cytochrome c oxidase histochemistry was applied as a metabolic brain mapping method. Rats were trained in a reference memory task using the Morris water maze, followed by an extinction procedure of the previously acquired memory task. Results show that rats learned successfully the spatial memory task as shown by the progressive decrease in measured latencies to reach the escape platform and the results obtained in the probe test. Spatial memory was subsequently extinguished as shown by the descending preference for the previously reinforced location. A control naïve group was added to ensure that brain metabolic changes were specifically related with performance in the spatial memory extinction task. Extinction of the original spatial learning task significantly modified the metabolic activity in the dorsal and ventral hippocampus, the amygdala and the mammillary bodies. Moreover, the ventral hippocampus, the lateral mammillary body and the retrosplenial cortex were differentially recruited in the spatial memory extinction task, as shown by group differences in brain metabolic networks. These findings provide new insights on the brain regions and functional brain networks underlying spatial memory, and specifically spatial memory extinction. © 2016 Wiley Periodicals, Inc.

  7. Spatial memory extinction differentially affects dorsal and ventral hippocampal metabolic activity and associated functional brain networks.

    PubMed

    Méndez-Couz, Marta; González-Pardo, Héctor; Vallejo, Guillermo; Arias, Jorge L; Conejo, Nélida M

    2016-10-01

    Previous studies showed the involvement of brain regions associated with both spatial learning and associative learning in spatial memory extinction, although the specific role of the dorsal and ventral hippocampus and the extended hippocampal system including the mammillary body in the process is still controversial. The present study aimed to identify the involvement of the dorsal and ventral hippocampus, together with cortical regions, the amygdaloid nuclei, and the mammillary bodies in the extinction of a spatial memory task. To address these issues, quantitative cytochrome c oxidase histochemistry was applied as a metabolic brain mapping method. Rats were trained in a reference memory task using the Morris water maze, followed by an extinction procedure of the previously acquired memory task. Results show that rats learned successfully the spatial memory task as shown by the progressive decrease in measured latencies to reach the escape platform and the results obtained in the probe test. Spatial memory was subsequently extinguished as shown by the descending preference for the previously reinforced location. A control naïve group was added to ensure that brain metabolic changes were specifically related with performance in the spatial memory extinction task. Extinction of the original spatial learning task significantly modified the metabolic activity in the dorsal and ventral hippocampus, the amygdala and the mammillary bodies. Moreover, the ventral hippocampus, the lateral mammillary body and the retrosplenial cortex were differentially recruited in the spatial memory extinction task, as shown by group differences in brain metabolic networks. These findings provide new insights on the brain regions and functional brain networks underlying spatial memory, and specifically spatial memory extinction. © 2016 Wiley Periodicals, Inc. PMID:27102086

  8. Cumulative frequency distribution of past species extinctions

    NASA Technical Reports Server (NTRS)

    Raup, D. M.

    1991-01-01

    Analysis of Sepkoski's compendium of the time ranges of 30,000+ taxa yields a mean duration of 28.4 ma for genera of fossil invertebrates. This converts to an average extinction rate of 3.5 percent per million years or about one percent every 286,000 years. Using survivorship techniques, these estimates can be converted to the species level, yielding a Phanerozoic average of one percent species extinction every 40,000 years. Variation in extinction rates through time is far greater than the null expectation of a homogeneous birth-death model and this reflects the well-known episodicity of extinction ranging from a few large mass extinctions to so-called background extinction. The observed variation in rates can be used to construct a cumulative frequency distribution of extinction intensity, and this distribution, in the form of a kill curve for species, shows the expected waiting times between extinction events of a given intensity. The kill curve is an average description of the extinction events of a given intensity. The kill curve is an average description of the extinction record and does not imply any cause or causes of extinction. The kill curve shows, among other things, that only about five percent of total species extinctions in the Phanerozoic were involved in the five largest mass extinctions. The other 95 percent were distributed among large and small events not normally called mass extinctions. As an exploration of the possibly absurd proposition that most past extinctions were produced by the effects of large-body impact, the kill curve for species was mapped on the comparable distribution for comet and asteroid impacts. The result is a curve predicting the species kill for a given size of impacting object (expressed as crater size). The results are reasonable in that impacts producing craters less than 30 km (diameter) cause negligible extinction but those producing craters 100-150 km (diameter) cause extinction of species in the range of 45

  9. Extinction and reinstatement of phasic dopamine signals in the nucleus accumbens core during Pavlovian conditioning.

    PubMed

    Sunsay, Ceyhun; Rebec, George V

    2014-10-01

    The prediction-error model of dopamine (DA) signaling has largely been confirmed with various appetitive Pavlovian conditioning procedures and has been supported in tests of Pavlovian extinction. Studies have repeatedly shown, however, that extinction does not erase the original memory of conditioning as the prediction-error model presumes, putting the model at odds with contemporary views that treat extinction as an episode of learning rather than unlearning of conditioning. Here, we combined fast-scan cyclic voltammetry (FSCV) with appetitive Pavlovian conditioning to assess DA release directly during extinction and reinstatement. DA was monitored in the nucleus accumbens core, which plays a key role in reward processing. Following at least 4 daily sessions of 16 tone-food pairings, fast-scan cyclic voltammetry was performed while rats received additional tone-food pairings followed by tone alone presentations (i.e., extinction). Acquisition memory was reinstated with noncontingent presentations of reward and then tested with cue presentation. Tone-food pairings produced transient (1- to 3-s) DA release in response to tone. During extinction, the amplitude of the DA response decreased significantly. Following presentation of 2 noncontingent food pellets, subsequent tone presentation reinstated the DA signal. Our results support the prediction-error model for appetitive Pavlovian extinction but not for reinstatement.

  10. The hypocretin/orexin system mediates the extinction of fear memories.

    PubMed

    Flores, África; Valls-Comamala, Victòria; Costa, Giulia; Saravia, Rocío; Maldonado, Rafael; Berrendero, Fernando

    2014-11-01

    Anxiety disorders are often associated with an inability to extinguish learned fear responses. The hypocretin/orexin system is involved in the regulation of emotional states and could also participate in the consolidation and extinction of aversive memories. Using hypocretin receptor-1 and hypocretin receptor-2 antagonists, hypocretin-1 and hypocretin-2 peptides, and hypocretin receptor-1 knockout mice, we investigated the role of the hypocretin system in cue- and context-dependent fear conditioning and extinction. Hypocretins were crucial for the consolidation of fear conditioning, and this effect was mainly observed in memories with a high emotional component. Notably, after the acquisition of fear memory, hypocretin receptor-1 blockade facilitated fear extinction, whereas hypocretin-1 administration impaired this extinction process. The extinction-facilitating effects of the hypocretin receptor-1 antagonist SB334867 were associated with increased expression of cFos in the basolateral amygdala and the infralimbic cortex. Intra-amygdala, but neither intra-infralimbic prefrontal cortex nor intra-dorsohippocampal infusion of SB334867 enhanced fear extinction. These results reveal a key role for hypocretins in the extinction of aversive memories and suggest that hypocretin receptor-1 blockade could represent a novel therapeutic target for the treatment of diseases associated with inappropriate retention of fear, such as post-traumatic stress disorder and phobias.

  11. Sexual selection protects against extinction.

    PubMed

    Lumley, Alyson J; Michalczyk, Łukasz; Kitson, James J N; Spurgin, Lewis G; Morrison, Catriona A; Godwin, Joanne L; Dickinson, Matthew E; Martin, Oliver Y; Emerson, Brent C; Chapman, Tracey; Gage, Matthew J G

    2015-06-25

    Reproduction through sex carries substantial costs, mainly because only half of sexual adults produce offspring. It has been theorized that these costs could be countered if sex allows sexual selection to clear the universal fitness constraint of mutation load. Under sexual selection, competition between (usually) males and mate choice by (usually) females create important intraspecific filters for reproductive success, so that only a subset of males gains paternity. If reproductive success under sexual selection is dependent on individual condition, which is contingent to mutation load, then sexually selected filtering through 'genic capture' could offset the costs of sex because it provides genetic benefits to populations. Here we test this theory experimentally by comparing whether populations with histories of strong versus weak sexual selection purge mutation load and resist extinction differently. After evolving replicate populations of the flour beetle Tribolium castaneum for 6 to 7 years under conditions that differed solely in the strengths of sexual selection, we revealed mutation load using inbreeding. Lineages from populations that had previously experienced strong sexual selection were resilient to extinction and maintained fitness under inbreeding, with some families continuing to survive after 20 generations of sib × sib mating. By contrast, lineages derived from populations that experienced weak or non-existent sexual selection showed rapid fitness declines under inbreeding, and all were extinct after generation 10. Multiple mutations across the genome with individually small effects can be difficult to clear, yet sum to a significant fitness load; our findings reveal that sexual selection reduces this load, improving population viability in the face of genetic stress.

  12. Sexual selection protects against extinction.

    PubMed

    Lumley, Alyson J; Michalczyk, Łukasz; Kitson, James J N; Spurgin, Lewis G; Morrison, Catriona A; Godwin, Joanne L; Dickinson, Matthew E; Martin, Oliver Y; Emerson, Brent C; Chapman, Tracey; Gage, Matthew J G

    2015-06-25

    Reproduction through sex carries substantial costs, mainly because only half of sexual adults produce offspring. It has been theorized that these costs could be countered if sex allows sexual selection to clear the universal fitness constraint of mutation load. Under sexual selection, competition between (usually) males and mate choice by (usually) females create important intraspecific filters for reproductive success, so that only a subset of males gains paternity. If reproductive success under sexual selection is dependent on individual condition, which is contingent to mutation load, then sexually selected filtering through 'genic capture' could offset the costs of sex because it provides genetic benefits to populations. Here we test this theory experimentally by comparing whether populations with histories of strong versus weak sexual selection purge mutation load and resist extinction differently. After evolving replicate populations of the flour beetle Tribolium castaneum for 6 to 7 years under conditions that differed solely in the strengths of sexual selection, we revealed mutation load using inbreeding. Lineages from populations that had previously experienced strong sexual selection were resilient to extinction and maintained fitness under inbreeding, with some families continuing to survive after 20 generations of sib × sib mating. By contrast, lineages derived from populations that experienced weak or non-existent sexual selection showed rapid fitness declines under inbreeding, and all were extinct after generation 10. Multiple mutations across the genome with individually small effects can be difficult to clear, yet sum to a significant fitness load; our findings reveal that sexual selection reduces this load, improving population viability in the face of genetic stress. PMID:25985178

  13. Light extinction in the atmosphere

    SciTech Connect

    Laulainen, N.

    1992-06-01

    Atmospheric aerosol particles originating from natural sources, such as volcanos and sulfur-bearing gas emissions from the oceans, and from human sources, such as sulfur emissions from fossil fuel combustion and biomass burning, strongly affect visual air quality and are suspected to significantly affect radiative climate forcing of the planet. During the daytime, aerosols obscure scenic vistas, while at night they diminish our ability to observe stellar objects. Scattering of light is the main means by which aerosols attenuate and redistribute light in the atmosphere and by which aerosols can alter and reduce visibility and potentially modify the energy balance of the planet. Trends and seasonal variability of atmospheric aerosol loading, such as column-integrated light extinction or optical depth, and how they may affect potential climate change have been difficult to quantify because there have been few observations made of important aerosol optical parameters, such as optical depth, over the globe and over time and often these are of uneven quality. To address questions related to possible climate change, there is a pressing need to acquire more high-quality aerosol optical depth data. Extensive deployment of improved solar radiometers over the next few years will provide higher-quality extinction data over a wider variety of locations worldwide. An often overlooked source of turbidity data, however, is available from astronomical observations, particularly stellar photoelectric photometry observations. With the exception of the Project ASTRA articles published almost 20 years ago, few of these data ever appear in the published literature. This paper will review the current status of atmospheric extinction observations, as highlighted by the ASTRA work and augmented by more recent solar radiometry measurements.

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

    PubMed Central

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

    2015-01-01

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

  15. Increased perceived self-efficacy facilitates the extinction of fear in healthy participants.

    PubMed

    Zlomuzica, Armin; Preusser, Friederike; Schneider, Silvia; Margraf, Jürgen

    2015-01-01

    Self-efficacy has been proposed as an important element of a successful cognitive behavioral treatment (CBT). Positive changes in perceived self-efficacy have been linked to an improved adaptive emotional and behavioral responding in the context of anxiety-provoking situations. Furthermore, a positive influence of increased self-efficacy on cognitive functions has been confirmed. The present study examined the effect of verbal persuasion on perceived self-efficacy and fear extinction. Healthy participants were subjected to a standardized differential fear conditioning paradigm. After fear acquisition, half of the participants received a verbal persuasion aimed at increasing perceived self-efficacy. The extinction of fear was assessed immediately thereafter on both the implicit and explicit level. Our results suggest that an increased perceived self-efficacy was associated with enhanced extinction, evidenced on the psychophysiological level and accompanied by more pronounced decrements in conditioned negative valence. Changes in extinction were not due to a decrease in overall emotional reactivity to conditioned stimuli (CS). In addition, debriefing participants about the false positive feedback did not affect the processing of already extinguished conditioned responses during a subsequent continued extinction phase. Our results suggest that positive changes in perceived self-efficacy can be beneficial for emotional learning. Findings are discussed with respect to strategies aimed at increasing extinction learning in the course of exposure-based treatments. PMID:26528152

  16. Increased perceived self-efficacy facilitates the extinction of fear in healthy participants

    PubMed Central

    Zlomuzica, Armin; Preusser, Friederike; Schneider, Silvia; Margraf, Jürgen

    2015-01-01

    Self-efficacy has been proposed as an important element of a successful cognitive behavioral treatment (CBT). Positive changes in perceived self-efficacy have been linked to an improved adaptive emotional and behavioral responding in the context of anxiety-provoking situations. Furthermore, a positive influence of increased self-efficacy on cognitive functions has been confirmed. The present study examined the effect of verbal persuasion on perceived self-efficacy and fear extinction. Healthy participants were subjected to a standardized differential fear conditioning paradigm. After fear acquisition, half of the participants received a verbal persuasion aimed at increasing perceived self-efficacy. The extinction of fear was assessed immediately thereafter on both the implicit and explicit level. Our results suggest that an increased perceived self-efficacy was associated with enhanced extinction, evidenced on the psychophysiological level and accompanied by more pronounced decrements in conditioned negative valence. Changes in extinction were not due to a decrease in overall emotional reactivity to conditioned stimuli (CS). In addition, debriefing participants about the false positive feedback did not affect the processing of already extinguished conditioned responses during a subsequent continued extinction phase. Our results suggest that positive changes in perceived self-efficacy can be beneficial for emotional learning. Findings are discussed with respect to strategies aimed at increasing extinction learning in the course of exposure-based treatments. PMID:26528152

  17. Fear conditioning and extinction in anxiety- and depression-prone persons.

    PubMed

    Dibbets, Pauline; van den Broek, Anne; Evers, Elisabeth A T

    2015-01-01

    Anxiety and depression frequently co-occur and may share similar deficits in the processing of emotional stimuli. High anxiety is associated with a failure in the acquisition and extinction of fear conditioning. Despite the supposed common deficits, no research has been conducted on fear acquisition and extinction in depression. The main aim of the present study was to investigate and compare fear acquisition and extinction in anxiety- and depression-prone participants. Non-clinical anxious, depressive, anxious-depressive and control participants performed a fear discrimination task. During acquisition, the CS+ predicted an aversive event (unconditioned stimulus, US) and the CS- safety (no US). During extinction, the CS+ was no longer followed by the US, rendering it (temporarily) into a safety signal. On each CS participants rated their US expectancy; skin conductance responses (SCRs) were measured throughout. The expectancy scores indicated that high anxiety resulted in less safety learning during acquisition and extinction; no effect of depression was observed. SCRs showed that high-anxiety persons displayed less discrimination learning (CS+ minus CS-) during acquisition than low-anxiety persons. During extinction, high-depression persons demonstrated more discriminative SCR than low-depression persons. The observed discrepancies in response patterns of high-anxiety and -depression persons seem to indicate distinctive information processing of emotional stimuli.

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

    PubMed

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

    2015-05-01

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

  19. Comment on the extinct paradox

    NASA Technical Reports Server (NTRS)

    Levine, D. M.

    1983-01-01

    The extinction paradox is a contradiction between geometrical optics results which predict that at high frequencies the scattering cross section of an object should equal its geometrical cross section and rigorous scattering theory which shows that at high frequencies the scattering cross section approaches twice the geometrical cross section of the object. Confusion about the reason for this paradox persists today even though the nature of the paradox was correctly identified many years ago by Brillouin. The resolution of the paradox is restated and illustrated with an example, and then the implications to the interpretation of scattering cross sections are identified.

  20. Microwave extinction characteristics of nanoparticle aggregates

    NASA Astrophysics Data System (ADS)

    Wu, Y. P.; Cheng, J. X.; Liu, X. X.; Wang, H. X.; Zhao, F. T.; Wen, W. W.

    2016-07-01

    Structure of nanoparticle aggregates plays an important role in microwave extinction capacity. The diffusion-limited aggregation model (DLA) for fractal growth is utilized to explore the possible structures of nanoparticle aggregates by computer simulation. Based on the discrete dipole approximation (DDA) method, the microwave extinction performance by different nano-carborundum aggregates is numerically analyzed. The effects of the particle quantity, original diameter, fractal structure, as well as orientation on microwave extinction are investigated, and also the extinction characteristics of aggregates are compared with the spherical nanoparticle in the same volume. Numerical results give out that proper aggregation of nanoparticle is beneficial to microwave extinction capacity, and the microwave extinction cross section by aggregated granules is better than that of the spherical solid one in the same volume.

  1. Presence and Acquired Origin of Reduced Recall for Fear Extinction in PTSD: Results of a Twin Study

    PubMed Central

    Milad, Mohammed R.; Orr, Scott P.; Lasko, Natasha B.; Chang, Yuchiao; Rauch, Scott L.; Pitman, Roger K.

    2008-01-01

    Recall of fear extinction, which is thought to aid in recovery from a psychologically traumatic event, is hypothesized to be deficient in post-traumatic stress disorder (PTSD), but this has not yet been demonstrated in the laboratory, nor has its origin been investigated. To address these two issues, 14 pairs of monozygotic twins discordant for combat exposure, in 7 of which the combat-exposed twin had PTSD, underwent a two-day fear conditioning and extinction procedure. On Day 1, subjects viewed colored light conditioned stimuli, some of which were paired with mild electric shock, followed by extinction of the conditioned responses. On Day 2, recall of Day 1 extinction learning (i.e., extinction retention) was assessed. Skin conductance response (SCR) was the dependent measure. There were no group differences during acquisition or extinction learning. However, a significant PTSD Diagnosis (in the exposed twin) x combat Exposure interaction emerged during extinction recall, with the PTSD combat veterans having larger SCRs than their own co-twins, and than the non-PTSD combat veterans and their co-twins. These results indicate that retention of extinction of conditioned fear is deficient in PTSD. Furthermore, they support the conclusion that this deficit is acquired as a result of combat trauma leading to PTSD, rather than being a predisposing factor to developing PTSD upon the stress of combat. PMID:18313695

  2. Aerosol extinction measurements with CO2-lidar

    NASA Technical Reports Server (NTRS)

    Hagard, Arne; Persson, Rolf

    1992-01-01

    With the aim to develop a model for infrared extinction due to aerosols in slant paths in the lower atmosphere we perform measurements with a CO2-lidar. Earlier measurements with a transmissometer along horizontal paths have been used to develop relations between aerosol extinction and meteorological parameters. With the lidar measurements we hope to develop corresponding relations for altitude profiles of the aerosol extinction in the infrared. An important application is prediction of detection range for infrared imaging systems.

  3. Acquisition, Extinction, Recovery, and Reversal of Different Response Sequences Under Conditional Control by Nicotine in Rats

    PubMed Central

    Troisi, Joseph R.

    2013-01-01

    Complex voluntary behaviors occur in sequence. Eight rats were trained in an operant procedure that used nicotine and non-drug (saline) states as interoceptive cues that signaled which of two behavioral sequences led to food reward. The distal and proximal responses in the chain were always maintained on variable interval 30-sec and fixed ratio-1 schedules, respectively, and rate differences between the responses were used as the dependent variable. Extinction and reversal training was conducted. Distal response rates were significantly greater than proximal response rates during training, testing, extinction, and reversal learning. These data suggest that (a) nicotine can establish interoceptive control over different response sequences, and (b) extinction of one response sequence may be state-dependent. The clinical relevance of extinction of complex behavioral repertoires such as drug-seeking and drug-taking behavior that are evoked by specific interoceptive cues is addressed in regard to drug abuse treatment and relapse. PMID:24837654

  4. Facilitation of extinction by an increase or a decrease in trial duration.

    PubMed

    Haselgrove, Mark; Pearce, John M

    2003-04-01

    Five experiments examined the effects of altering the duration of a conditioned stimulus (CS) for extinction. For the first 3 experiments, rats received conditioning with a 10-s CS before different groups received extinction with a CS that was either the same duration or longer than that used for conditioning. For the remaining 2 experiments, conditioning was conducted with a 60-s CS before different groups received extinction with a CS of either the same duration or a shorter duration than that used for conditioning. In all experiments, extinction progressed more readily when the CS duration was different for the 2 stages than when it was constant. The results are discussed in terms of rate expectancy theory and associative learning theory.

  5. The dorsal bundle extinction effect:dependence on subtle changes in acquisition.

    PubMed

    Mason, S T; Fibiger, H C

    1979-04-27

    Destruction of the ascending noradrenergic innervation to the forebrain in rats by intracerebral injection of the selective neurotoxin 6-hydroxydopamine (4 microgram in 2 microliter injected bilaterally into the dorsal bundle in the mesencephalon) was found to cause resistance to extinction of a continuously reinforced lever press response. However, this effect occurred only if the lesion were present during acquisition training on the reinforced schedule and not if intact animals were trained and the lesion inflicted after completion of acquisition training and just prior to the extinction phase. Thus, the behavioural effect that manifests itself during extinction appears to be due to subtle changes in the acquisition learning process. This is consistent with the predictions of an attentional theory of noradrenergic function and appears to exclude most other suggested explanations of the dorsal bundle extinction effect.

  6. Impaired extinction of fear conditioning after REM deprivation is magnified by rearing in an enriched environment.

    PubMed

    Hunter, Amy Silvestri

    2015-07-01

    Evidence from both human and animal studies indicates that rapid eye movement sleep (REM) is essential for the acquisition and retention of information, particularly of an emotional nature. Learning and memory can also be impacted by manipulation of housing condition such as exposure to an enriched environment (EE). This study investigated the effects of REM deprivation and EE, both separately and combined, on the extinction of conditioned fear in rats. Consistent with prior studies, conditioning was enhanced in EE-reared rats and extinction was impaired in REM deprived rats. In addition, rats exposed to both REM deprivation and EE showed the greatest impairment in extinction, with effects persisting through the first two days of extinction training. This study is the first to explore the combination of REM deprivation and EE and suggests that manipulations that alter sleep, particularly REM, can have persisting deleterious effects on emotional memory processing.

  7. Secondary extinction in Pavlovian fear conditioning.

    PubMed

    Vurbic, Drina; Bouton, Mark E

    2011-09-01

    Pavlov (1927/1960) reported that following the conditioning of several stimuli, extinction of one conditioned stimulus (CS) attenuated responding to others that had not undergone direct extinction. However, this secondary extinction effect has not been widely replicated in the contemporary literature. In three conditioned suppression experiments with rats, we further explored the phenomenon. In Experiment 1, we asked whether secondary extinction is more likely to occur with target CSs that have themselves undergone some prior extinction. A robust secondary extinction effect was obtained with a nonextinguished target CS. Experiment 2 showed that extinction of one CS was sufficient to reduce renewal of a second CS when it was tested in a neutral (nonextinction) context. In Experiment 3, secondary extinction was observed in groups that initially received intermixed conditioning trials with the target and nontarget CSs, but not in groups that received conditioning of the two CSs in separate sessions. The results are consistent with the hypothesis that CSs must be associated with a common temporal context during conditioning for secondary extinction to occur.

  8. Mass extinctions vs. uniformitarianism in biological evolution

    SciTech Connect

    Bak, P.; Paczuski, M.

    1995-12-31

    It is usually believed that Darwin`s theory leads to a smooth gradual evolution, so that mass extinctions must be caused by external shocks. However, it has recently been argued that mass extinctions arise from the intrinsic dynamics of Darwinian evolution. Species become extinct when swept by intermittent avalanches propagating through the global ecology. These ideas are made concrete through studies of simple mathematical models of co-evolving species. The models exhibit self-organized criticality and describe some general features of the extinction pattern in the fossil record.

  9. Lumbar lordosis of extinct hominins.

    PubMed

    Been, Ella; Gómez-Olivencia, Asier; Kramer, Patricia A

    2012-01-01

    The lordotic curvature of the lumbar spine (lumbar lordosis) in humans is a critical component in the ability to achieve upright posture and bipedal gait. Only general estimates of the lordotic angle (LA) of extinct hominins are currently available, most of which are based on the wedging of the vertebral bodies. Recently, a new method for calculating the LA in skeletal material has become available. This method is based on the relationship between the lordotic curvature and the orientation of the inferior articular processes relative to vertebral bodies in the lumbar spines of living primates. Using this relationship, we developed new regression models in order to calculate the LAs in hominins. The new models are based on primate group-means and were used to calculate the LAs in the spines of eight extinct hominins. The results were also compared with the LAs of modern humans and modern nonhuman apes. The lordotic angles of australopithecines (41° ± 4), H. erectus (45°) and fossil H. sapiens (54° ± 14) are similar to those of modern humans (51° ± 11). This analysis confirms the assumption that human-like lordotic curvature was a morphological change that took place during the acquisition of erect posture and bipedalism as the habitual form of locomotion. Neandertals have smaller lordotic angles (LA = 29° ± 4) than modern humans, but higher angles than nonhuman apes (22° ± 3). This suggests possible subtle differences in Neandertal posture and locomotion from that of modern humans. PMID:22052243

  10. LIDAR for measuring atmospheric extinction

    NASA Astrophysics Data System (ADS)

    Dawsey, M.; Gimmestad, G.; Roberts, D.; McGraw, J.; Zimmer, P.; Fitch, J.

    2006-06-01

    The Georgia Tech Research Institute and the University of New Mexico are developing a compact, rugged, eye safe lidar (laser radar) to be used specifically for measuring atmospheric extinction in support of the second generation of the CCD/Transit Instrument (CTI-II). The CTI-II is a 1.8 meter telescope that will be used to accomplish a precise timedomain imaging photometric and astrometric survey at the McDonald Observatory in West Texas. The supporting lidar will enable more precise photometry by providing real-time measurements of the amount of atmospheric extinction as well as its cause, i.e. low-lying aerosols, dust or smoke in the free troposphere, or high cirrus. The goal of this project is to develop reliable, cost-effective lidar technology for any observatory. The lidar data can be used to efficiently allocate observatory time and to provide greater integrity for ground-based data. The design is described in this paper along with estimates of the lidar's performance.

  11. Lumbar lordosis of extinct hominins.

    PubMed

    Been, Ella; Gómez-Olivencia, Asier; Kramer, Patricia A

    2012-01-01

    The lordotic curvature of the lumbar spine (lumbar lordosis) in humans is a critical component in the ability to achieve upright posture and bipedal gait. Only general estimates of the lordotic angle (LA) of extinct hominins are currently available, most of which are based on the wedging of the vertebral bodies. Recently, a new method for calculating the LA in skeletal material has become available. This method is based on the relationship between the lordotic curvature and the orientation of the inferior articular processes relative to vertebral bodies in the lumbar spines of living primates. Using this relationship, we developed new regression models in order to calculate the LAs in hominins. The new models are based on primate group-means and were used to calculate the LAs in the spines of eight extinct hominins. The results were also compared with the LAs of modern humans and modern nonhuman apes. The lordotic angles of australopithecines (41° ± 4), H. erectus (45°) and fossil H. sapiens (54° ± 14) are similar to those of modern humans (51° ± 11). This analysis confirms the assumption that human-like lordotic curvature was a morphological change that took place during the acquisition of erect posture and bipedalism as the habitual form of locomotion. Neandertals have smaller lordotic angles (LA = 29° ± 4) than modern humans, but higher angles than nonhuman apes (22° ± 3). This suggests possible subtle differences in Neandertal posture and locomotion from that of modern humans.

  12. Phylogenetic Clustering of Origination and Extinction across the Late Ordovician Mass Extinction.

    PubMed

    Krug, Andrew Z; Patzkowsky, Mark E

    2015-01-01

    Mass extinctions can have dramatic effects on the trajectory of life, but in some cases the effects can be relatively small even when extinction rates are high. For example, the Late Ordovician mass extinction is the second most severe in terms of the proportion of genera eliminated, yet is noted for the lack of ecological consequences and shifts in clade dominance. By comparison, the end-Cretaceous mass extinction was less severe but eliminated several major clades while some rare surviving clades diversified in the Paleogene. This disconnect may be better understood by incorporating the phylogenetic relatedness of taxa into studies of mass extinctions, as the factors driving extinction and recovery are thought to be phylogenetically conserved and should therefore promote both origination and extinction of closely related taxa. Here, we test whether there was phylogenetic selectivity in extinction and origination using brachiopod genera from the Middle Ordovician through the Devonian. Using an index of taxonomic clustering (RCL) as a proxy for phylogenetic clustering, we find that A) both extinctions and originations shift from taxonomically random or weakly clustered within families in the Ordovician to strongly clustered in the Silurian and Devonian, beginning with the recovery following the Late Ordovician mass extinction, and B) the Late Ordovician mass extinction was itself only weakly clustered. Both results stand in stark contrast to Cretaceous-Cenozoic bivalves, which showed significant levels of taxonomic clustering of extinctions in the Cretaceous, including strong clustering in the mass extinction, but taxonomically random extinctions in the Cenozoic. The contrasting patterns between the Late Ordovician and end-Cretaceous events suggest a complex relationship between the phylogenetic selectivity of mass extinctions and the long-term phylogenetic signal in origination and extinction patterns.

  13. Phylogenetic Clustering of Origination and Extinction across the Late Ordovician Mass Extinction.

    PubMed

    Krug, Andrew Z; Patzkowsky, Mark E

    2015-01-01

    Mass extinctions can have dramatic effects on the trajectory of life, but in some cases the effects can be relatively small even when extinction rates are high. For example, the Late Ordovician mass extinction is the second most severe in terms of the proportion of genera eliminated, yet is noted for the lack of ecological consequences and shifts in clade dominance. By comparison, the end-Cretaceous mass extinction was less severe but eliminated several major clades while some rare surviving clades diversified in the Paleogene. This disconnect may be better understood by incorporating the phylogenetic relatedness of taxa into studies of mass extinctions, as the factors driving extinction and recovery are thought to be phylogenetically conserved and should therefore promote both origination and extinction of closely related taxa. Here, we test whether there was phylogenetic selectivity in extinction and origination using brachiopod genera from the Middle Ordovician through the Devonian. Using an index of taxonomic clustering (RCL) as a proxy for phylogenetic clustering, we find that A) both extinctions and originations shift from taxonomically random or weakly clustered within families in the Ordovician to strongly clustered in the Silurian and Devonian, beginning with the recovery following the Late Ordovician mass extinction, and B) the Late Ordovician mass extinction was itself only weakly clustered. Both results stand in stark contrast to Cretaceous-Cenozoic bivalves, which showed significant levels of taxonomic clustering of extinctions in the Cretaceous, including strong clustering in the mass extinction, but taxonomically random extinctions in the Cenozoic. The contrasting patterns between the Late Ordovician and end-Cretaceous events suggest a complex relationship between the phylogenetic selectivity of mass extinctions and the long-term phylogenetic signal in origination and extinction patterns. PMID:26658946

  14. Phylogenetic Clustering of Origination and Extinction across the Late Ordovician Mass Extinction

    PubMed Central

    Krug, Andrew Z.; Patzkowsky, Mark E.

    2015-01-01

    Mass extinctions can have dramatic effects on the trajectory of life, but in some cases the effects can be relatively small even when extinction rates are high. For example, the Late Ordovician mass extinction is the second most severe in terms of the proportion of genera eliminated, yet is noted for the lack of ecological consequences and shifts in clade dominance. By comparison, the end-Cretaceous mass extinction was less severe but eliminated several major clades while some rare surviving clades diversified in the Paleogene. This disconnect may be better understood by incorporating the phylogenetic relatedness of taxa into studies of mass extinctions, as the factors driving extinction and recovery are thought to be phylogenetically conserved and should therefore promote both origination and extinction of closely related taxa. Here, we test whether there was phylogenetic selectivity in extinction and origination using brachiopod genera from the Middle Ordovician through the Devonian. Using an index of taxonomic clustering (RCL) as a proxy for phylogenetic clustering, we find that A) both extinctions and originations shift from taxonomically random or weakly clustered within families in the Ordovician to strongly clustered in the Silurian and Devonian, beginning with the recovery following the Late Ordovician mass extinction, and B) the Late Ordovician mass extinction was itself only weakly clustered. Both results stand in stark contrast to Cretaceous-Cenozoic bivalves, which showed significant levels of taxonomic clustering of extinctions in the Cretaceous, including strong clustering in the mass extinction, but taxonomically random extinctions in the Cenozoic. The contrasting patterns between the Late Ordovician and end-Cretaceous events suggest a complex relationship between the phylogenetic selectivity of mass extinctions and the long-term phylogenetic signal in origination and extinction patterns. PMID:26658946

  15. Involvement of BDNF signaling transmission from basolateral amygdala to infralimbic prefrontal cortex in conditioned taste aversion extinction.

    PubMed

    Xin, Jian; Ma, Ling; Zhang, Tian-Yi; Yu, Hui; Wang, Yue; Kong, Liang; Chen, Zhe-Yu

    2014-05-21

    Brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin-related kinase receptor B (TrkB), play a critical role in memory extinction. However, the detailed role of BDNF in memory extinction on the basis of neural circuit has not been fully understood. Here, we aim to investigate the role of BDNF signaling circuit in mediating conditioned taste aversion (CTA) memory extinction of the rats. We found region-specific changes in BDNF gene expression during CTA extinction. CTA extinction led to increased BDNF gene expression in the basolateral amygdala (BLA) and infralimbic prefrontal cortex (IL) but not in the central amygdaloid nucleus (CeA) and hippocampus (HIP). Moreover, blocking BDNF signaling or exogenous microinjection of BDNF into the BLA or IL could disrupt or enhance CTA extinction, which suggested that BDNF signaling in the BLA and IL is necessary and sufficient for CTA extinction. Interestingly, we found that microinjection of BDNF-neutralizing antibody into the BLA could abolish the extinction training-induced BDNF mRNA level increase in the IL, but not vice versa, demonstrating that BDNF signaling is transmitted from the BLA to IL during extinction. Finally, the accelerated extinction learning by infusion of exogenous BDNF in the BLA could also be blocked by IL infusion of BDNF-neutralizing antibody rather than vice versa, indicating that the IL, but not BLA, is the primary action site of BDNF in CTA extinction. Together, these data suggest that BLA-IL circuit regulates CTA memory extinction by identifying BDNF as a key regulator.

  16. Serotonin transporter polyadenylation polymorphism modulates the retention of fear extinction memory.

    PubMed

    Hartley, Catherine A; McKenna, Morgan C; Salman, Rabia; Holmes, Andrew; Casey, B J; Phelps, Elizabeth A; Glatt, Charles E

    2012-04-01

    Growing evidence suggests serotonin's role in anxiety and depression is mediated by its effects on learned fear associations. Pharmacological and genetic manipulations of serotonin signaling in mice alter the retention of fear extinction learning, which is inversely associated with anxious temperament in mice and humans. Here, we test whether genetic variation in serotonin signaling in the form of a common human serotonin transporter polyadenylation polymorphism (STPP/rs3813034) is associated with spontaneous fear recovery after extinction. We show that the risk allele of this polymorphism is associated with impaired retention of fear extinction memory and heightened anxiety and depressive symptoms. These STPP associations in humans mirror the phenotypic effects of serotonin transporter knockout in mice, highlighting the STPP as a potential genetic locus underlying interindividual differences in serotonin transporter function in humans. Furthermore, we show that the serotonin transporter polyadenylation profile associated with the STPP risk allele is altered through the chronic administration of fluoxetine, a treatment that also facilitates retention of extinction learning. The propensity to form persistent fear associations due to poor extinction recall may be an intermediate phenotype mediating the effects of genetic variation in serotonergic function on anxiety and depression. The consistency and specificity of these data across species provide robust support for this hypothesis and suggest that the little-studied STPP may be an important risk factor for mood and anxiety disorders in humans.

  17. Rhubarb leaves poisoning

    MedlinePlus

    ... in the leaves (leaf blade) of the rhubarb plant. The stalk can be eaten. ... may include: Breathing difficulty Burning in the mouth Burning in the throat Coma Diarrhea Eye pain Kidney stones Nausea and vomiting Red-colored urine Seizures Stomach pain Weakness

  18. Leaves: Nature's Solar Collectors

    ERIC Educational Resources Information Center

    Isabelle, Aaron D.; de Groot, Cornelis

    2009-01-01

    One of the most captivating things about plants is the way they capture the Sun's energy, but this can be a difficult topic to cover with elementary students. Therefore, to help students to make a concrete connection to this abstract concept, this series of solar-energy lessons focuses on leaves and how they act as "solar collectors." As students…

  19. Maternity Leave in Taiwan

    ERIC Educational Resources Information Center

    Feng, Joyce Yen; Han, Wen-Jui

    2010-01-01

    Using the first nationally representative birth cohort study in Taiwan, this paper examines the role that maternity leave policy in Taiwan plays in the timing of mothers returning to work after giving birth, as well as the extent to which this timing is linked to the amount of time mothers spend with their children and their use of breast milk…

  20. Maternity Leave in Taiwan

    PubMed Central

    Feng, Joyce Yen; Han, Wen-Jui

    2011-01-01

    Using the first nationally representative birth cohort study in Taiwan, this paper examines the role that maternity leave policy in Taiwan plays in the timing of mothers returning to work after giving birth, as well as the extent to which this timing is linked to the amount of time mothers spend with their children and their use of breast milk versus formula. We found that the time when mothers returned to work coincided with the duration of guaranteed leave. In particular, mothers with a labor pension plan resumed work significantly earlier than mothers with no pension plan, and mothers with no pension plan returned to work significantly later than those with pension plans. The short leave of absence guaranteed under existing policies translated into mothers spending less time with their children and being more likely to exclusively use formula by 6 months after birth. In contrast, mothers who resumed work later than 6 months after birth were more likely to have not worked before birth or to have quit their jobs during pregnancy. Implications and recommendations for parental leave policy in Taiwan are discussed. PMID:21603074

  1. Opioid receptors in the midbrain periaqueductal gray regulate extinction of pavlovian fear conditioning.

    PubMed

    McNally, Gavan P; Pigg, Michael; Weidemann, Gabrielle

    2004-08-01

    Four experiments studied the role of opioid receptors in the midbrain periaqueductal gray matter (PAG), an important structure eliciting conditioned fear responses, in the extinction of Pavlovian fear. Rats received pairings of an auditory conditioned stimulus (CS) with a foot shock unconditioned stimulus (US). The freezing conditioned response (CR) elicited by the CS was then extinguished via nonreinforced presentations of the CS. Microinjection of the opioid receptor antagonist naloxone into the ventrolateral PAG (vlPAG) before nonrein-forced CS presentations impaired development of extinction, but such microinjections at the end of extinction did not reinstate an already extinguished freezing CR. This role for opioid receptors in fear extinction was specific to the vlPAG because infusions of naloxone into the dorsal PAG did not impair fear extinction. Finally, the impairment of fear extinction produced by vlPAG infusions of naloxone was dose-dependent. These results show for the first time that the midbrain PAG contributes to fear extinction and specifically identify a role for vlPAG opioid receptors in the acquisition but not the expression of such extinction. Taken together with our previous findings, we suggest that, during fear conditioning, activation of vlPAG opioid receptors contributes to detection of the discrepancy between the actual and expected outcome of the conditioning trial. vlPAG opioid receptors regulate the learning that accrues to the CS and other stimuli present on a trial because they instantiate an associative error correction process influencing US information reaching the site of CS-US convergence in the amygdala. During nonreinforcement, this vlPAG opioid receptor contribution signals extinction.

  2. D-cycloserine to enhance extinction of cue-elicited craving for alcohol: a translational approach.

    PubMed

    MacKillop, J; Few, L R; Stojek, M K; Murphy, C M; Malutinok, S F; Johnson, F T; Hofmann, S G; McGeary, J E; Swift, R M; Monti, P M

    2015-01-01

    Cue-elicited craving for alcohol is well established but extinction-based treatment to extinguish this response has generated only modest positive outcomes in clinical trials. Basic and clinical research suggests that D-cycloserine (DCS) enhances extinction to fear cues under certain conditions. However, it remains unclear whether DCS would also accelerate extinction of cue-elicited craving for alcohol. The goal of the current study was to examine whether, compared with placebo (PBO), DCS enhanced extinction of cue-elicited craving among treatment-seeking individuals with alcohol use disorders (AUDs). Participants were administered DCS (50 mg) or PBO 1 h before an alcohol extinction paradigm in a simulated bar environment on two occasions. The extinction procedures occurred 1 week apart and were fully integrated into outpatient treatment. Subjective craving for alcohol was the primary variable of interest. Follow-up cue reactivity sessions were conducted 1 week and 3 weeks later to ascertain persisting DCS effects. Drinking outcomes and tolerability were also examined. DCS was associated with augmented reductions in alcohol craving to alcohol cues during the first extinction session and these effects persisted through all subsequent sessions, suggesting facilitation of extinction. Participants in the DCS condition reported significant short-term reductions in drinking, although these did not persist to follow-up, and found the medication highly tolerable. These findings provide evidence that DCS enhances extinction of cue-elicited craving for alcohol in individuals with AUDs in the context of outpatient treatment. The potential clinical utility of DCS is discussed, including methodological considerations and context-dependent learning. PMID:25849983

  3. The influence of partner cues on the extinction of causal judgments in people.

    PubMed

    Holmes, Nathan M; Griffiths, Oren; Westbrook, R Frederick

    2014-09-01

    Studies in laboratory animals have shown that the extinction of a conditioned stimulus, A, is regulated by the associative history of a second stimulus, X, when the two are extinguished in simultaneous compound: An inhibitory X protects A from extinction (Rescorla Learning & Behavior, 31, 124-132, 2003), whereas an excitatory X facilitates, and under some circumstances deepens, the extinction of A (Rescorla Journal of Experimental Psychology: Animal Behavior Processes, 26, 251-260, 2000, Journal of Experimental Psychology: Animal Behavior Processes, 32, 135-144, 2006). In the present study, we used the allergist task to examine whether the extinction of causal judgments in people is similarly regulated by the causal status of co-present stimuli. Experiment 1 showed that a cue trained as a conditioned inhibitor protected a target cue from extinction: The target extinguished in compound with the inhibitor was rated as being more causal of the outcome than was a target extinguished in compound with a control cue lacking inhibitory properties. In contrast, the remaining experiments showed that the extinction of a target cue was regulated by the presence, but not the causal status, of a partner cue: Target cues extinguished in compound were protected from extinction, and no evidence showed that an already extinguished partner conferred more protection (Exp. 2), or that an excitatory partner conferred any less protection (Exps. 2 and 3), or that an excitatory partner deepened the extinction of its already extinguished target. These findings are inconsistent with elemental models that rely on a common error term to explain associative changes in extinction. They are largely, but not completely, consistent with the configural model proposed by Pearce (Psychological Review, 94, 61-73, 1987), which predicts an ordering of levels of protection that was not observed.

  4. D-cycloserine to enhance extinction of cue-elicited craving for alcohol: a translational approach.

    PubMed

    MacKillop, J; Few, L R; Stojek, M K; Murphy, C M; Malutinok, S F; Johnson, F T; Hofmann, S G; McGeary, J E; Swift, R M; Monti, P M

    2015-04-07

    Cue-elicited craving for alcohol is well established but extinction-based treatment to extinguish this response has generated only modest positive outcomes in clinical trials. Basic and clinical research suggests that D-cycloserine (DCS) enhances extinction to fear cues under certain conditions. However, it remains unclear whether DCS would also accelerate extinction of cue-elicited craving for alcohol. The goal of the current study was to examine whether, compared with placebo (PBO), DCS enhanced extinction of cue-elicited craving among treatment-seeking individuals with alcohol use disorders (AUDs). Participants were administered DCS (50 mg) or PBO 1 h before an alcohol extinction paradigm in a simulated bar environment on two occasions. The extinction procedures occurred 1 week apart and were fully integrated into outpatient treatment. Subjective craving for alcohol was the primary variable of interest. Follow-up cue reactivity sessions were conducted 1 week and 3 weeks later to ascertain persisting DCS effects. Drinking outcomes and tolerability were also examined. DCS was associated with augmented reductions in alcohol craving to alcohol cues during the first extinction session and these effects persisted through all subsequent sessions, suggesting facilitation of extinction. Participants in the DCS condition reported significant short-term reductions in drinking, although these did not persist to follow-up, and found the medication highly tolerable. These findings provide evidence that DCS enhances extinction of cue-elicited craving for alcohol in individuals with AUDs in the context of outpatient treatment. The potential clinical utility of DCS is discussed, including methodological considerations and context-dependent learning.

  5. Constraints on Enhanced Extinction Resulting from Extinction Treatment in the Presence of an Added Excitor

    ERIC Educational Resources Information Center

    Urcelay, Gonzalo P.; Lipatova, Olga; Miller, Ralph R.

    2009-01-01

    Three Pavlovian fear conditioning experiments with rats as subjects explored the effect of extinction in the presence of a concurrent excitor. Our aim was to explore this particular treatment, documented in previous studies to deepen extinction, with novel control groups to shed light on the processes involved in extinction. Relative to subjects…

  6. Extinction and the spatial dynamics of biodiversity

    PubMed Central

    Jablonski, David

    2008-01-01

    The fossil record amply shows that the spatial fabric of extinction has profoundly shaped the biosphere; this spatial dimension provides a powerful context for integration of paleontological and neontological approaches. Mass extinctions evidently alter extinction selectivity, with many factors losing effectiveness except for a positive relation between survivorship and geographic range at the clade level (confirmed in reanalyses of end-Cretaceous extinction data). This relation probably also holds during “normal” times, but changes both slope and intercept with increasing extinction. The strong geographical component to clade dynamics can obscure causation in the extinction of a feature or a clade, owing to hitchhiking effects on geographic range, so that multifactorial analyses are needed. Some extinctions are spatially complex, and regional extinctions might either reset a diversity ceiling or create a diversification debt open to further diversification or invasion. Evolutionary recoveries also exhibit spatial dynamics, including regional differences in invasibilty, and expansion of clades from the tropics fuels at least some recoveries, as well as biodiversity dynamics during normal times. Incumbency effects apparently correlate more closely with extinction intensities than with standing diversities, so that regions with higher local and global extinctions are more subject to invasion; the latest Cenozoic temperate zones evidently received more invaders than the tropics or poles, but this dynamic could shift dramatically if tropical diversity is strongly depleted. The fossil record can provide valuable insights, and their application to present-day issues will be enhanced by partitioning past and present-day extinctions by driving mechanism rather than emphasizing intensity. PMID:18695229

  7. Orexin/hypocretin receptor 1 signaling mediates Pavlovian cue-food conditioning and extinction.

    PubMed

    Keefer, Sara E; Cole, Sindy; Petrovich, Gorica D

    2016-08-01

    Learned food cues can drive feeding in the absence of hunger, and orexin/hypocretin signaling is necessary for this type of overeating. The current study examined whether orexin also mediates cue-food learning during the acquisition and extinction of these associations. In Experiment 1, rats underwent two sessions of Pavlovian appetitive conditioning, consisting of tone-food presentations. Prior to each session, rats received either the orexin 1 receptor antagonist SB-334867 (SB) or vehicle systemically. SB treatment did not affect conditioned responses during the first conditioning session, measured as food cup behavior during the tone and latency to approach the food cup after the tone onset, compared to the vehicle group. During the second conditioning session, SB treatment attenuated learning. All groups that received SB, prior to either the first or second conditioning session, displayed significantly less food cup behavior and had longer latencies to approach the food cup after tone onset compared to the vehicle group. These findings suggest orexin signaling at the 1 receptor mediates the consolidation and recall of cue-food acquisition. In Experiment 2, another group of rats underwent tone-food conditioning sessions (drug free), followed by two extinction sessions under either SB or vehicle treatment. Similar to Experiment 1, SB did not affect conditioned responses during the first session. During the second extinction session, the group that received SB prior to the first extinction session, but vehicle prior to the second, expressed conditioned food cup responses longer after tone offset, when the pellets were previously delivered during conditioning, and maintained shorter latencies to approach the food cup compared to the other groups. The persistence of these conditioned behaviors indicates impairment in extinction consolidation due to SB treatment during the first extinction session. Together, these results demonstrate an important role for orexin

  8. Orexin/hypocretin receptor 1 signaling mediates Pavlovian cue-food conditioning and extinction.

    PubMed

    Keefer, Sara E; Cole, Sindy; Petrovich, Gorica D

    2016-08-01

    Learned food cues can drive feeding in the absence of hunger, and orexin/hypocretin signaling is necessary for this type of overeating. The current study examined whether orexin also mediates cue-food learning during the acquisition and extinction of these associations. In Experiment 1, rats underwent two sessions of Pavlovian appetitive conditioning, consisting of tone-food presentations. Prior to each session, rats received either the orexin 1 receptor antagonist SB-334867 (SB) or vehicle systemically. SB treatment did not affect conditioned responses during the first conditioning session, measured as food cup behavior during the tone and latency to approach the food cup after the tone onset, compared to the vehicle group. During the second conditioning session, SB treatment attenuated learning. All groups that received SB, prior to either the first or second conditioning session, displayed significantly less food cup behavior and had longer latencies to approach the food cup after tone onset compared to the vehicle group. These findings suggest orexin signaling at the 1 receptor mediates the consolidation and recall of cue-food acquisition. In Experiment 2, another group of rats underwent tone-food conditioning sessions (drug free), followed by two extinction sessions under either SB or vehicle treatment. Similar to Experiment 1, SB did not affect conditioned responses during the first session. During the second extinction session, the group that received SB prior to the first extinction session, but vehicle prior to the second, expressed conditioned food cup responses longer after tone offset, when the pellets were previously delivered during conditioning, and maintained shorter latencies to approach the food cup compared to the other groups. The persistence of these conditioned behaviors indicates impairment in extinction consolidation due to SB treatment during the first extinction session. Together, these results demonstrate an important role for orexin

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

    PubMed Central

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

    2016-01-01

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

  10. Pharmacological facilitation of fear extinction and the search for adjunct treatments for anxiety disorders--the case of yohimbine.

    PubMed

    Holmes, Andrew; Quirk, Gregory J

    2010-01-01

    There is current interest in identifying drugs that facilitate fear extinction, as this form of learning is the basis of certain cognitive therapies for anxiety disorders. Following an initial report several years ago that the alpha2-adrenoreceptor antagonist yohimbine facilitated extinction in mice, more recent studies have shown mixed effects or even impairment. It has become clear that the effect of yohimbine on extinction depends on a number of factors, including genetic background, contextual variables and the presence of competing behaviors. To what extent theses effects of yohimbine are mediated through the alpha2-adrenoreceptor, as opposed to other sites of action, is also uncertain. More work is needed before this drug can be approved as a pharmacological adjunct for extinction-based therapies. More generally, the case of yohimbine may serve as a model for the development of other extinction facilitators.

  11. Periodicity of extinction: A 1988 update

    NASA Technical Reports Server (NTRS)

    Sepkowski, J. John, Jr.

    1988-01-01

    The hypothesis that events of mass extinction recur periodically at approximately 26 my intervals is an empirical claim based on analysis of data from the fossil record. The hypothesis has become closely linked with catastrophism because several events in the periodic series are associated with evidence of extraterrestrial impacts, and terrestrial forcing mechanisms with long, periodic recurrences are not easily conceived. Astronomical mechanisms that have been hypothesized include undetected solar companions and solar oscillation about the galactic plane, which induce comet showers and result in impacts on Earth at regular intervals. Because these mechanisms are speculative, they have been the subject of considerable controversy, as has the hypothesis of periodicity of extinction. In response to criticisms and uncertainties, a data base was developed on times of extinction of marine animal genera. A time series is given and analyzed with 49 sample points for the per-genus extinction rate from the Late Permian to the Recent. An unexpected pattern in the data is the uniformity of magnitude of many of the periodic extinction events. Observations suggest that the sequence of extinction events might be the result of two sets of mechanisms: a periodic forcing that normally induces only moderate amounts of extinction, and independent incidents or catastrophes that, when coincident with the periodic forcing, amplify its signal and produce major-mass extinctions.

  12. Catastrophic extinctions follow deforestation in Singapore.

    PubMed

    Brook, Barry W; Sodhi, Navjot S; Ng, Peter K L

    2003-07-24

    The looming mass extinction of biodiversity in the humid tropics is a major concern for the future, yet most reports of extinctions in these regions are anecdotal or conjectural, with a scarcity of robust, broad-based empirical data. Here we report on local extinctions among a wide range of terrestrial and freshwater taxa from Singapore (540 km2) in relation to habitat loss exceeding 95% over 183 years. Substantial rates of documented and inferred extinctions were found, especially for forest specialists, with the greatest proportion of extinct taxa (34-87%) in butterflies, fish, birds and mammals. Observed extinctions were generally fewer, but inferred losses often higher, in vascular plants, phasmids, decapods, amphibians and reptiles (5-80%). Forest reserves comprising only 0.25% of Singapore's area now harbour over 50% of the residual native biodiversity. Extrapolations of the observed and inferred local extinction data, using a calibrated species-area model, imply that the current unprecedented rate of habitat destruction in Southeast Asia will result in the loss of 13-42% of regional populations over the next century, at least half of which will represent global species extinctions.

  13. Current extinction rates of reptiles and amphibians.

    PubMed

    Alroy, John

    2015-10-20

    There is broad concern that a mass extinction of amphibians and reptiles is now underway. Here I apply an extremely conservative Bayesian method to estimate the number of recent amphibian and squamate extinctions in nine important tropical and subtropical regions. The data stem from a combination of museum collection databases and published site surveys. The method computes an extinction probability for each species by considering its sighting frequency and last sighting date. It infers hardly any extinction when collection dates are randomized and it provides underestimates when artificial extinction events are imposed. The method also appears to be insensitive to trends in sampling; therefore, the counts it provides are absolute minimums. Extinctions or severe population crashes have accumulated steadily since the 1970s and 1980s, and at least 3.1% of frog species have already disappeared. Based on these data and this conservative method, the best estimate of the global grand total is roughly 200 extinctions. Consistent with previous results, frog losses are heavy in Latin America, which has been greatly affected by the pathogenic chytrid fungus Batrachochytrium dendrobatidis. Extinction rates are now four orders-of-magnitude higher than background, and at least another 6.9% of all frog species may be lost within the next century, even if there is no acceleration in the growth of environmental threats.

  14. Current extinction rates of reptiles and amphibians.

    PubMed

    Alroy, John

    2015-10-20

    There is broad concern that a mass extinction of amphibians and reptiles is now underway. Here I apply an extremely conservative Bayesian method to estimate the number of recent amphibian and squamate extinctions in nine important tropical and subtropical regions. The data stem from a combination of museum collection databases and published site surveys. The method computes an extinction probability for each species by considering its sighting frequency and last sighting date. It infers hardly any extinction when collection dates are randomized and it provides underestimates when artificial extinction events are imposed. The method also appears to be insensitive to trends in sampling; therefore, the counts it provides are absolute minimums. Extinctions or severe population crashes have accumulated steadily since the 1970s and 1980s, and at least 3.1% of frog species have already disappeared. Based on these data and this conservative method, the best estimate of the global grand total is roughly 200 extinctions. Consistent with previous results, frog losses are heavy in Latin America, which has been greatly affected by the pathogenic chytrid fungus Batrachochytrium dendrobatidis. Extinction rates are now four orders-of-magnitude higher than background, and at least another 6.9% of all frog species may be lost within the next century, even if there is no acceleration in the growth of environmental threats. PMID:26438855

  15. Current extinction rates of reptiles and amphibians

    PubMed Central

    Alroy, John

    2015-01-01

    There is broad concern that a mass extinction of amphibians and reptiles is now underway. Here I apply an extremely conservative Bayesian method to estimate the number of recent amphibian and squamate extinctions in nine important tropical and subtropical regions. The data stem from a combination of museum collection databases and published site surveys. The method computes an extinction probability for each species by considering its sighting frequency and last sighting date. It infers hardly any extinction when collection dates are randomized and it provides underestimates when artificial extinction events are imposed. The method also appears to be insensitive to trends in sampling; therefore, the counts it provides are absolute minimums. Extinctions or severe population crashes have accumulated steadily since the 1970s and 1980s, and at least 3.1% of frog species have already disappeared. Based on these data and this conservative method, the best estimate of the global grand total is roughly 200 extinctions. Consistent with previous results, frog losses are heavy in Latin America, which has been greatly affected by the pathogenic chytrid fungus Batrachochytrium dendrobatidis. Extinction rates are now four orders-of-magnitude higher than background, and at least another 6.9% of all frog species may be lost within the next century, even if there is no acceleration in the growth of environmental threats. PMID:26438855

  16. Survival without recovery after mass extinctions

    PubMed Central

    Jablonski, David

    2002-01-01

    Because many survivors of mass extinctions do not participate in postrecovery diversifications, and therefore fall into a pattern that can be termed “Dead Clade Walking” (DCW), the effects of mass extinctions extend beyond the losses observed during the event itself. Analyses at two taxonomic levels provide a first-order test of the prevalence of DCWs by using simple and very conservative operational criteria. For four of the Big Five mass extinctions of the Phanerozoic, the marine genera that survived the extinction suffered ≈10–20% attrition in the immediately following geologic stage that was significantly greater than the losses sustained in preextinction stages. The stages immediately following the three Paleozoic mass extinctions also account for 17% of all order-level losses in marine invertebrates over that interval, which is, again, significantly greater than that seen for the other stratigraphic stages (no orders are lost immediately after the end-Triassic or end-Cretaceous mass extinctions). DCWs are not evenly distributed among four regional molluscan time-series following the end-Cretaceous extinction, demonstrating the importance of spatial patterns in recovery dynamics. Although biotic interactions have been invoked to explain the differential postextinction success of clades, such hypotheses must be tested against alternatives that include stochastic processes in low-diversity lineages—which is evidently not a general explanation for the ordinal DCW patterns, because postextinction fates are not related to the size of extinction bottlenecks in Paleozoic orders—and ongoing physical environmental changes. PMID:12060760

  17. Immediate extinction promotes the return of fear.

    PubMed

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

    2016-05-01

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

  18. Extinction-Induced Variability in Human Behavior

    ERIC Educational Resources Information Center

    Kinloch, Jennifer M.; Foster, T. Mary; McEwan, James S. A.

    2009-01-01

    Participants earned points by pressing a computer space bar (Experiment 1) or forming rectangles on the screen with the mouse (Experiment 2) under differential-reinforcement-of-low-rate schedules, followed by extinction. Variability in interresponse time (the contingent dimension) increased during extinction, as for Morgan and Lee (1996);…

  19. Survival without recovery after mass extinctions.

    PubMed

    Jablonski, David

    2002-06-11

    Because many survivors of mass