Gershman, Samuel J.; Blei, David M.; Niv, Yael
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…
Furini, Cristiane; Myskiw, Jociane; Izquierdo, Ivan
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.
Quirk, Gregory J.; Mueller, Devin
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
Myskiw, Jociane C; Izquierdo, Ivan; Furini, Cristiane R G
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.
Meir Drexler, Shira; Hamacher-Dang, Tanja C; Wolf, Oliver T
In extinction learning, the individual learns that a previously acquired association (e.g. between a threat and its predictor) is no longer valid. This learning is the principle underlying many cognitive-behavioral psychotherapeutic treatments, e.g. 'exposure therapy'. However, extinction is often highly-context dependent, leading to renewal (relapse of extinguished conditioned response following context change). We have previously shown that post-extinction stress leads to a more context-dependent extinction memory in a predictive learning task. Yet as stress prior to learning can impair the integration of contextual cues, here we aim to create a more generalized extinction memory by inducing stress prior to extinction. Forty-nine men and women learned the associations between stimuli and outcomes in a predictive learning task (day 1), extinguished them shortly after an exposure to a stress/control condition (day 2), and were tested for renewal (day 3). No group differences were seen in acquisition and extinction learning, and a renewal effect was present in both groups. However, the groups differed in the strength and context-dependency of the extinction memory. Compared to the control group, the stress group showed an overall reduced recovery of responding to the extinguished stimuli, in particular in the acquisition context. These results, together with our previous findings, demonstrate that the effects of stress exposure on extinction memory depend on its timing. While post-extinction stress makes the memory more context-bound, pre-extinction stress strengthens its consolidation for the acquisition context as well, making it potentially more resistant to relapse. These results have implications for the use of glucocorticoids as extinction-enhancers in exposure therapy.
Wilson, Marlene A; Fadel, Jim R
Cholinergic activation regulates cognitive function, particularly long-term memory consolidation. This Review presents an overview of the anatomical, neurochemical, and pharmacological evidence supporting the cholinergic regulation of Pavlovian contextual and cue-conditioned fear learning and extinction. Basal forebrain cholinergic neurons provide inputs to neocortical regions and subcortical limbic structures such as the hippocampus and amygdala. Pharmacological manipulations of muscarinic and nicotinic receptors support the role of cholinergic processes in the amygdala, hippocampus, and prefrontal cortex in modulating the learning and extinction of contexts or cues associated with threat. Additional evidence from lesion studies and analysis of in vivo acetylcholine release with microdialysis similarly support a critical role of cholinergic neurotransmission in corticoamygdalar or corticohippocampal circuits during acquisition of fear extinction. Although a few studies have suggested a complex role of cholinergic neurotransmission in the cellular plasticity essential for extinction learning, more work is required to elucidate the exact cholinergic mechanisms and physiological role of muscarinic and nicotinic receptors in these fear circuits. Such studies are important for elucidating the role of cholinergic neurotransmission in disorders such as posttraumatic stress disorder that involve deficits in extinction learning as well as for developing novel therapeutic approaches for such disorders. © 2016 Wiley Periodicals, Inc.
The endocannabinoid system has emerged as a versatile neuromodulatory system, implicated in a plethora of physiological and pathophysiological processes. Cannabinoid receptor type 1 (CB1 receptor) and endocannabinoids are widely distributed in the brain. Their roles in learning and memory have been well documented, using rodents in various memory tests. Depending on the test, the endocannabinoid system is required in the acquisition and/or extinction of memory. In particular, the activation of CB1 receptor-mediated signaling is centrally involved in the facilitation of behavioral adaptation after the acquisition of aversive memories. As several human psychiatric disorders, such as phobia, generalized anxiety disorders, and posttraumatic stress disorder (PTSD) appear to involve aberrant memory processing and impaired adaptation to changed environmental conditions, the hope has been fuelled that the endocannabinoid system might be a valuable therapeutic target for the treatment of these disorders. This review summarizes the current data on the role of the endocannabinoid system in the modulation of extinction learning.
Morís, Joaquín; Barberia, Itxaso; Vadillo, Miguel A.; Andrades, Ainhoa; López, Francisco J.
Extinction is a very relevant learning phenomenon from a theoretical and applied point of view. One of its most relevant features is that relapse phenomena often take place once the extinction training has been completed. Accordingly, as extinction-based therapies constitute the most widespread empirically validated treatment of anxiety disorders,…
Wang, Melissa E; Yuan, Robin K; Keinath, Alexander T; Ramos Álvarez, Manuel M; Muzzio, Isabel A
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.
Wang, Melissa E.; Yuan, Robin K.; Keinath, Alexander T.; Ramos Álvarez, Manuel M.
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
Chang, D-I; Lissek, S; Ernst, T M; Thürling, M; Uengoer, M; Tegenthoff, M; Ladd, M E; Timmann, D
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
Woodruff, Elizabeth R.; Greenwood, Benjamin N.; Chun, Lauren E.; Fardi, Sara; Hinds, Laura R.; Spencer, Robert L.
Post Traumatic Stress Disorder (PTSD) is associated with altered conditioned fear extinction expression and impaired circadian function including dysregulation of glucocorticoid hormone secretion. We examined in adult male rats the relationship between conditioned fear extinction learning, circadian phase, and endogenous glucocorticoids (CORT). Rats maintained on a 12 hr light:dark cycle were trained and tested across 3 separate daily sessions (conditioned fear acquisition and 2 extinction sessions) that were administered during either the rats’ active or inactive circadian phase. In an initial experiment we found that rats at both circadian phases acquired and extinguished auditory cue conditioned fear to a similar degree in the first extinction session. However, rats trained and tested at zeitgeber time-16 (ZT16) (active phase) showed enhanced extinction memory expression during the second extinction session compared to rats trained and tested at ZT4 (inactive phase). In a follow-up experiment, adrenalectomized (ADX) or sham surgery rats were similarly trained and tested across 3 separate daily sessions at either ZT4 or ZT16. ADX had no effect on conditioned fear acquisition or conditioned fear memory. Sham ADX rats trained and tested at ZT16 exhibited better extinction learning across the two extinction sessions compared to all other groups of rats. These results indicate that conditioned fear extinction learning is modulated by time of day, and this diurnal modulation requires the presence of adrenal hormones. These results support an important role of CORT-dependent circadian processes in regulating conditioned fear extinction learning, which may be capitalized upon to optimize effective treatment of PTSD. PMID:25746455
Woodruff, Elizabeth R; Greenwood, Benjamin N; Chun, Lauren E; Fardi, Sara; Hinds, Laura R; Spencer, Robert L
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.
Young, M B; Andero, R; Ressler, K J; Howell, L L
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
Young, M B; Andero, R; Ressler, K J; Howell, L L
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.
Cavallo, Joel S.; Hamilton, Brittany N.; Farley, Joseph
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
Eisenhardt, Dorothea; Menzel, Randolf
Retrieving a consolidated memory--by exposing an animal to the learned stimulus but not to the associated reinforcement--leads to two opposing processes: one that weakens the old memory as a result of extinction learning, and another that strengthens the old, already-consolidated memory as a result of some less well-understood form of learning. This latter process of memory strengthening is often referred to as "reconsolidation", since protein synthesis can inhibit this form of memory formation. Although the behavioral phenomena of the two antagonizing forms of learning are well documented, the mechanisms behind the corresponding processes of memory formation are still quite controversial. Referring to results of extinction/reconsolidation experiments in honeybees, we argue that two opposing learning processes--with their respective consolidation phases and memories--are initiated by retrieval trials: extinction learning and reminder learning, the latter leading to the phenomenon of spontaneous recovery from extinction, a process that can be blocked with protein synthesis inhibition.
Riddle, Megan C; McKenna, Morgan C; Yoon, Yone J; Pattwell, Siobhan S; Santos, Patricia Mae G; Casey, B J; Glatt, Charles E
Fear extinction learning, the ability to reassess a learned cue of danger as safe when it no longer predicts aversive events, is often dysregulated in anxiety disorders. Selective serotonin reuptake inhibitors (SSRI's) enhance neural plasticity and their ability to enhance fear extinction learning may explain their anxiolytic properties. Caloric restriction (CR) has SSRI-like effects on neural plasticity and anxiety-related behavior. We implemented CR in mice to determine its effects on conditioned-fear responses. Wild type and serotonin transporter (SERT) knockout mice underwent CR for 7 days leading to significant weight loss. Mice were then tested for cued fear learning and anxiety-related behavior. CR markedly enhanced fear extinction learning and its retention in adolescent female mice, and adults of both sexes. These effects of CR were absent in SERT knockout mice. Moreover, CR phenocopied behavioral and molecular effects of chronic fluoxetine, but there was no additive effect of CR in fluoxetine-treated mice. These results demonstrate that CR enhances fear extinction learning through a SERT-dependent mechanism. These results may have implications for eating disorders such as anorexia nervosa (AN), in which there is a high prevalence of anxiety before the onset of dietary restriction and support proposals that in AN, CR is a motivated effort to control dysregulated fear responses and elevated anxiety.
Redish, A. David; Jensen, Steve; Johnson, Adam; Kurth-Nelson, Zeb
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…
Langton, Julia M.; Richardson, Rick
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…
Ouyang, Ming; Thomas, Steven A
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.
Morriss, Jayne; Christakou, Anastasia; van Reekum, Carien M
Extinction-resistant fear is considered to be a central feature of pathological anxiety. Here we sought to determine if individual differences in Intolerance of Uncertainty (IU), a potential risk factor for anxiety disorders, underlies compromised fear extinction. We tested this hypothesis by recording electrodermal activity in 38 healthy participants during fear acquisition and extinction. We assessed the temporality of fear extinction, by examining early and late extinction learning. During early extinction, low IU was associated with larger skin conductance responses to learned threat vs. safety cues, whereas high IU was associated with skin conductance responding to both threat and safety cues, but no cue discrimination. During late extinction, low IU showed no difference in skin conductance between learned threat and safety cues, whilst high IU predicted continued fear expression to learned threat, indexed by larger skin conductance to threat vs. safety cues. These findings suggest a critical role of uncertainty-based mechanisms in the maintenance of learned fear.
Lissek, Silke; Glaubitz, Benjamin; Güntürkün, Onur; Tegenthoff, Martin
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
Fenton, Georgina E; Halliday, David M; Mason, Rob; Bredy, Timothy W; Stevenson, Carl W
Sex differences in learned fear expression and extinction involve the medial prefrontal cortex (mPFC). We recently demonstrated that enhanced learned fear expression during auditory fear extinction and its recall is linked to persistent theta activation in the prelimbic (PL) but not infralimbic (IL) cortex of female rats. Emerging evidence indicates that gamma oscillations in mPFC are also implicated in the expression and extinction of learned fear. Therefore we re-examined our in vivo electrophysiology data and found that females showed persistent PL gamma activation during extinction and a failure of IL gamma activation during extinction recall. Altered prefrontal gamma oscillations thus accompany sex differences in learned fear expression and its extinction. These findings are relevant for understanding the neural basis of post-traumatic stress disorder, which is more prevalent in women and involves impaired extinction and mPFC dysfunction.
Long, Virginia A; Fanselow, Michael S
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.
Baker, Kathryn D.; Richardson, Rick
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.…
Oh, Jeong Rok; Park, Cho Hyun; Jo, Sung Jun
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…
Griffiths, Oren; Holmes, Nathan; Westbrook, R. Fred
Models of associative learning have proposed that cue-outcome learning critically depends on the degree of prediction error encountered during training. Two experiments examined the role of error-driven extinction learning in a human causal learning task. Target cues underwent extinction in the presence of additional cues, which differed in the degree to which they predicted the outcome, thereby manipulating outcome expectancy and, in the absence of any change in reinforcement, prediction error. These prediction error manipulations have each been shown to modulate extinction learning in aversive conditioning studies. While both manipulations resulted in increased prediction error during training, neither enhanced extinction in the present human learning task (one manipulation resulted in less extinction at test). The results are discussed with reference to the types of associations that are regulated by prediction error, the types of error terms involved in their regulation, and how these interact with parameters involved in training. PMID:28232809
Hefner, Kathryn; Whittle, Nigel; Juhasz, Jaynann; Norcross, Maxine; Karlsson, Rose-Marie; Saksida, Lisa M; Bussey, Timothy J; Singewald, Nicolas; Holmes, Andrew
Fear extinction is a form of new learning that results in the inhibition of conditioned fear. Trait deficits in fear extinction are a risk factor for anxiety disorders. There are few examples of naturally occurring animal models of impaired extinction. The present study compared fear extinction in a panel of inbred mouse strains. This strain survey revealed an impairment in fear extinction in 129/SvImJ (129S1). The phenotypic specificity of this deficit was evaluated by comparing 129S1 and C57BL/6J for one-trial and multitrial fear conditioning, nociception, and extinction of conditioned taste aversion and an appetitive instrumental response. 129S1 were tested for sensitivity to the extinction-facilitating effects of extended training, as well as d-cycloserine and yohimbine treatment. To elucidate the neural basis of impaired 129S1 fear extinction, c-Fos and Zif268 expression was mapped after extinction recall. Results showed that impaired fear extinction in 129S1 was unrelated to altered fear conditioning or nociception, and was dissociable from intact appetitive extinction. Yohimbine treatment facilitated extinction in 129S1, but neither extended extinction training nor d-cycloserine treatment improved 129S1 extinction. After extinction recall, 129S1 showed reduced c-Fos and Zif268 expression in the infralimbic cortex and basolateral amygdala, and elevated c-Fos or Zif268 expression in central nucleus of the amygdala and medial paracapsular intercalated cell mass, relative to C57BL/6J. Collectively, these data demonstrate a deficit in fear extinction in 129S1 associated with a failure to properly engage corticolimbic extinction circuitry. This common inbred strain provides a novel model for studying impaired fear extinction in anxiety disorders.
Hefner, Kathryn; Whittle, Nigel; Juhasz, Jaynann; Norcross, Maxine; Karlsson, Rose-Marie; Saksida, Lisa M.; Bussey, Timothy J.; Singewald, Nicolas; Holmes, Andrew
Fear extinction is a form of new learning that results in the inhibition of conditioned fear. Trait deficits in fear extinction are a risk factor for anxiety disorders. There are few examples of naturally-occurring animal models of impaired extinction. The present study compared fear extinction in a panel of inbred mouse strains. This strain survey revealed an impairment in fear extinction in 129/SvImJ (129S1). The phenotypic specificity of this deficit was evaluated by comparing 129S1 and C57BL/6J for one-trial and multi-trial fear conditioning, nociception, and extinction of conditioned taste aversion (CTA) and an appetitive instrumental response. 129S1 were tested for sensitivity to the extinction-facilitating effects of extended training, as well as D-cycloserine and yohimbine treatment. To elucidate the neural basis of impaired 129S1 fear extinction, c-Fos and Zif268 expression was mapped following extinction recall. Results showed that impaired fear extinction in 129S1 was unrelated to altered fear conditioning or nociception, and was dissociable from intact appetitive extinction. Yohimbine treatment facilitated extinction in 129S1, but neither extended extinction training nor D-cycloserine treatment improved 129S1 extinction. Following extinction recall, 129S1 showed reduced c-Fos and Zif268 expression in the infralimbic cortex and basolateral amygdala, and elevated c-Fos or Zif268 expression in central nucleus of the amygdala and medial paracapsular intercalated cell mass, relative to C57BL/6J. Collectively, these data demonstrate a deficit in fear extinction in 129S1 associated with a failure to properly engage corticolimbic extinction circuitry. This common inbred strain provides a novel model for studying impaired fear extinction in anxiety disorders. PMID:18685032
Rabinak, Christine A; Angstadt, Mike; Lyons, Maryssa; Mori, Shoko; Milad, Mohammed R; Liberzon, Israel; Phan, K Luan
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.
Ellison, G; Handel, J; Rogers, R; Weiss, J
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.
Felsenberg, Johannes; Dombrowski, Vincent; Eisenhardt, Dorothea
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…
Thompson, Brittany M.; Baratta, Michael V.; Biedenkapp, Joseph C.; Rudy, Jerry W.; Watkins, Linda R.; Maier, Steven F.
Activation of the infralimbic region (IL) of the medial prefrontal cortex (mPFC) reduces conditioned fear in a variety of situations, and the IL is thought to play an important role in the extinction of conditioned fear. Here we report a series of experiments using contextual fear conditioning in which the IL is activated with the GABAa antagonist picrotoxin (Ptx) during a single extinction session in the fear context. We investigate the impact of this manipulation on subsequent extinction sessions in which Ptx is no longer present. First, we demonstrate that a single treatment with intra-IL Ptx administered in a conditioned fear context greatly accelerates the rate of extinction on the following days. Importantly, IL-Ptx also enhances extinction to a different fear context than the one in which IL-Ptx was administered. Thus, IL-Ptx primes extinction learning regardless of the fear context in which the IL was initially activated. Second, activation of the IL must occur in conjunction with a fear context in order to enhance extinction; the extinction enhancing effect is not observable if IL-Ptx is administered in a neutral context. Finally, this extinction enhancing effect is specific to the IL for it does not occur if Ptx is injected into the prelimbic region (PL) of the mPFC. The results indicate a novel persisting control of fear induced by activation of the IL and suggest that IL activation induces changes in extinction-related circuitry that prime extinction learning. PMID:21041382
Lommen, Miriam J J; Engelhard, Iris M; Sijbrandij, Marit; van den Hout, Marcel A; Hermans, Dirk
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.
Merz, Christian Josef; Hermann, Andrea; Stark, Rudolf; Wolf, Oliver Tobias
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.
Holtzman-Assif, Orit; Laurent, Vincent; Westbrook, R. Frederick
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…
Baeyens, Frank; Vansteenwegen, Debora; Beckers, Tom; Hermans, Dirk; Kerkhof, Ineke; De Ceulaer, Annick
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…
Rosas, Juan M.; Callejas-Aguilera, Jose E.
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…
Effting, Marieke; Vervliet, Bram; Beckers, Tom; Kindt, Merel
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…
Robert, Théo; Frasnelli, Elisa; Collett, Thomas S; Hempel de Ibarra, Natalie
Female bees and wasps demonstrate, through their performance of elaborate learning flights, when and where they memorise features of a significant site. An important feature of these flights is that the insects look back to fixate the site that they are leaving. Females, which forage for nectar and pollen and return with it to the nest, execute learning flights on their initial departure from both their nest and newly discovered flowers. To our knowledge, these flights have so far only been studied in females. Here, we describe and analyse putative learning flights observed in male bumblebees Bombus terrestris L. Once male bumblebees are mature, they leave their nest for good and fend for themselves. We show that, unlike female foragers, males always fly directly away from their nest, without looking back, in keeping with their indifference to their natal nest. In contrast, after males have drunk from artificial flowers, their flights on first leaving the flowers resemble the learning flights of females, particularly in their fixation of the flowers. These differences in the occurrence of female and male learning flights seem to match the diverse needs of the two sexes to learn about disparate, ecologically relevant places in their surroundings.
Self, David W; Choi, Kwang-Ho
Chronic drug use weakens excitatory neocortical input to the nucleus accumbens (NAc). We previously reported that extinction training, a form of inhibitory learning that progressively reduces cocaine-seeking behaviour when reward is withheld, reverses this deficit by up-regulating GluR1 and GluR2/3 subunits of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) glutamate receptors in the NAc. The level of GluR1 up-regulation is positively associated with a reduction in cocaine seeking, suggesting that extinction-induced up-regulation in AMPA receptors in the NAc opposes motivational influences that maintain cocaine seeking. This hypothesis is supported by the finding that over-expression of GluR1 and GluR2 in the NAc facilitates extinction of cocaine self-administration. Furthermore, a single extinction training session conducted during GluR1 and GluR2 over-expression strongly and selectively attenuates the ability of an environmental stressor to trigger relapse to cocaine seeking long after GluR1 and GluR2 over-expression declines. These results could suggest that excitatory input to the NAc promotes extinction learning, but only when memory is recalled under stressful situations. Recent studies indicate that both environmental stress and the frustrative stress of withholding reward during extinction of drug self-administration induce similar neurochemical events in the NAc. These neurochemical events could impose a "state-dependency" on extinction learning such that subsequent exposure to stress acts as a cue to enhance retrieval of extinction memory. Our results suggest that extinction-induced up-regulation in NAc AMPA receptors acts reciprocally to facilitate state-dependent extinction learning, as stressful situations evoke extinction memories that exert powerful inhibitory control over drug-seeking behaviour. These results may have important therapeutic implications for behaviour-based approaches aimed at treating drug addiction.
Redish, A David; Jensen, Steve; Johnson, Adam; Kurth-Nelson, Zeb
Because learned associations are quickly renewed following extinction, the extinction process must include processes other than unlearning. However, reinforcement learning models, such as the temporal difference reinforcement learning (TDRL) model, treat extinction as an unlearning of associated value and are thus unable to capture renewal. TDRL models are based on the hypothesis that dopamine carries a reward prediction error signal; these models predict reward by driving that reward error to zero. The authors construct a TDRL model that can accommodate extinction and renewal through two simple processes: (a) a TDRL process that learns the value of situation-action pairs and (b) a situation recognition process that categorizes the observed cues into situations. This model has implications for dysfunctional states, including relapse after addiction and problem gambling.
Rabinak, Christine A.; Angstadt, Mike; Lyons, Maryssa; Mori, Shoko; Milad, Mohammed R.; Liberzon, Israel; Phan, K. Luan
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
Gong, Zhiwen; Wang, Chao; Nieh, James C; Tan, Ken
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.
Bisby, James A; King, John A; Sulpizio, Valentina; Degeilh, Fanny; Valerie Curran, H; Burgess, Neil
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.
Childs, Jessica E; Alvarez-Dieppa, Amanda C; McIntyre, Christa K; Kroener, Sven
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.
de Kleine, Rianne A; Smits, Jasper A J; Hendriks, Gert-Jan; Becker, Eni S; van Minnen, Agnes
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.
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.
Golisch, Anne; Heba, Stefanie; Glaubitz, Benjamin; Tegenthoff, Martin; Lissek, Silke
A distributed network including prefrontal and hippocampal regions is involved in context-related extinction learning as well as in renewal. Renewal describes the recovery of an extinguished response if the context of extinction differs from the context of recall. Animal studies have demonstrated that prefrontal, but not hippocampal N-methyl-D-aspartate receptor (NMDAR) antagonism disrupted extinction learning and processing of task context. However, human studies of NMDAR in extinction learning are lacking, while NMDAR antagonism yielded contradictory results in other learning tasks. This fMRI study investigated the role of NMDAR for human behavioral and brain activation correlates of extinction and renewal. Healthy volunteers received a single dose of the NMDAR antagonist memantine prior to extinction of previously acquired stimulus-outcome associations presented in either identical or novel contexts. We observed better, and partly faster, extinction learning in participants receiving the NMDAR antagonist compared to placebo. However, memantine did not affect renewal. In both extinction and recall, the memantine group showed a deactivation in extinction-related brain regions, particularly in the prefrontal cortex, while hippocampal activity was increased. This higher hippocampal activation was in turn associated with the participants' body mass index (BMI) and extinction errors. Our results demonstrate potentially dose-related enhancing effects of memantine and highlight involvement of hippocampal NMDAR in context-related extinction learning. PMID:28326025
Moran, Anan; Katz, Donald B
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.
Dunsmoor, Joseph E.; Niv, Yael; Daw, Nathaniel; Phelps, Elizabeth A.
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
Dunsmoor, Joseph E; Niv, Yael; Daw, Nathaniel; Phelps, Elizabeth A
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.
Hadad-Ophir, Osnat; Brande-Eilat, Noa; Richter-Levin, Gal
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.
Ewald, Heike; Glotzbach-Schoon, Evelyn; Gerdes, Antje B. M.; Andreatta, Marta; Müller, Mathias; Mühlberger, Andreas; Pauli, Paul
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
Hadad-Ophir, Osnat; Brande-Eilat, Noa; Richter-Levin, Gal
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
Gass, J. T.; Chandler, L. J.
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
Todd, Travis P; Vurbic, Drina; Bouton, Mark E
This article reviews research on the behavioral and neural mechanisms of extinction as it is represented in both Pavlovian and instrumental learning. In Pavlovian extinction, repeated presentation of a signal without its reinforcer weakens behavior evoked by the signal; in instrumental extinction, repeated occurrence of a voluntary action without its reinforcer weakens the strength of the action. In either case, contemporary research at both the behavioral and neural levels of analysis has been guided by a set of extinction principles that were first generated by research conducted at the behavioral level. The review discusses these principles and illustrates how they have informed the study of both Pavlovian and instrumental extinction. It shows that behavioral and neurobiological research efforts have been tightly linked and that their results are readily integrated. Pavlovian and instrumental extinction are also controlled by compatible behavioral and neural processes. Since many behavioral effects observed in extinction can be multiply determined, we suggest that the current close connection between behavioral-level and neural-level analyses will need to continue.
André, Marion Agnès Emma; Manahan-Vaughan, Denise
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
Iordanova, Mihaela D.; Deroche, Mickael L. D.; Esber, Guillem R.; Schoenbaum, Geoffrey
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
Pijl, Sip Jan; Frostad, Per; Mjaavatn, Per Egil
During their secondary school years, a considerable number of students seriously consider choosing between learning and leaving. Leaving school early means that students do not complete their education. Early school leaving is the last step in a process in which students gradually lose interest and develop the intention to leave school. This study…
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
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.
Engelhard, Iris M; Leer, Arne; Lange, Emma; Olatunji, Bunmi O
Learned disgust appears to play an important role in certain anxiety disorders, and can be explained by the process of evaluative conditioning, in which an affective evaluative reaction evoked by an unconditional stimulus (US) is transferred to a conditional stimulus (CS). Much remains unknown about how disgust-related evaluative learning can be effectively eliminated. Study 1 of the present investigation examined the effects of extinction on reducing the negative evaluation of a CS that was acquired during disgust conditioning. Participants completed acquisition trials, with a disgusting picture as US and two neutral pictures as CS (CS+ was paired with the US; CS- was unpaired), followed by extinction trials ("CS only"; experimental condition) or a filler task (control condition). Extinction trials reduced acquired US expectancy to the CS+, but did not extinguish negative evaluations of the CS+. Study 2 examined the effects of counterconditioning on evaluative learned disgust. After disgust acquisition trials, counterconditioning trials followed in which the CS+ was paired with a pleasant US (experimental condition) or a filler task (control condition). Counterconditioning trials reduced acquired US expectancy to the CS+ and reduced evaluative conditioned disgust. Implications of the potential differential effects of extinction and counterconditioning on evaluative learning for exposure-based treatment of specific anxiety disorders are discussed.
Bouton, Mark E
The modern world is saturated with highly palatable and highly available food, providing many opportunities to associate food with environmental cues and actions (through Pavlovian and operant or instrumental learning, respectively). Basic learning processes can often increase the tendency to approach and consume food, whereas extinction, in which Pavlovian and operant behaviors decline when the reinforcer is withheld, weakens but does not erase those tendencies. Contemporary research suggests that extinction involves an inhibitory form of new learning that appears fragile because it is highly dependent on the context for expression. These ideas are supported by the phenomena of renewal, spontaneous recovery, resurgence, reinstatement, and rapid reacquisition in appetitive learning, which together may help explain why overeating may be difficult to suppress permanently, and why appetitive behavior may seem so persistent.
Auchter, Allison M.; Shumake, Jason; Gonzalez-Lima, Francisco; Monfils, Marie H.
Many factors account for how well individuals extinguish conditioned fears, such as genetic variability, learning capacity and conditions under which extinction training is administered. We predicted that memory-based interventions would be more effective to reduce the reinstatement of fear in subjects genetically predisposed to display more extinction learning. We tested this hypothesis in rats genetically selected for differences in fear extinction using two strategies: (1) attenuation of fear memory using post-retrieval extinction training, and (2) pharmacological enhancement of the extinction memory after extinction training by low-dose USP methylene blue (MB). Subjects selectively bred for divergent extinction phenotypes were fear conditioned to a tone stimulus and administered either standard extinction training or retrieval + extinction. Following extinction, subjects received injections of saline or MB. Both reconsolidation updating and MB administration showed beneficial effects in preventing fear reinstatement, but differed in the groups they targeted. Reconsolidation updating showed an overall effect in reducing fear reinstatement, whereas pharmacological memory enhancement using MB was an effective strategy, but only for individuals who were responsive to extinction.
Song, Mihee; Jo, Yong Sang; Lee, Yeon-Kyung; Choi, June-Seek
The lateral habenula (LHb) is an epithalamic brain structure that provides strong projections to midbrain monoaminergic systems that are involved in motivation, emotion, and reinforcement learning. LHb neurons are known to convey information about aversive outcomes and negative prediction errors, suggesting a role in learning from aversive events. To test this idea, we examined the effects of electrolytic lesions of the LHb on signaled two-way active avoidance learning in which rats were trained to avoid an unconditioned stimulus (US) by taking a proactive shuttling response to an auditory conditioned stimulus (CS). The lesioned animals learned the avoidance response significantly faster than the control groups. In a separate experiment, we also investigated whether the LHb contributes to Pavlovian threat (fear) conditioning and extinction. Following paired presentations of the CS and the US, LHb-lesioned animals showed normal acquisition of conditioned response (CR) measured with freezing. However, extinction of the CR in the subsequent CS-only session was significantly faster. The enhanced performance in avoidance learning and in threat extinction jointly suggests that the LHb normally plays an inhibitory role in learning driven by absence of aversive outcomes.
Vianna, Monica R; Coitinho, Adriana S; Izquierdo, Ivan
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.
Bliss, Joanne M; Gray, Erin E; Dhaka, Ajay; O'Dell, Thomas J; Colicelli, John
The amygdala is known to have a crucial role in both the acquisition and extinction of conditioned fear, but the physiological changes and biochemical mechanisms underlying these forms of learning are only partly understood. The Ras effector Rin1 activates Abl tyrosine kinases and Rab5 GTPases and is highly expressed in mature neurons of the telencephalon including the amygdala, where it inhibits the acquisition of fear memories (Rin1(-/-) mice show enhanced learning of conditioned fear). Here we report that Rin1(-/-) mice exhibit profound deficits in both latent inhibition and fear extinction, suggesting a critical role for Rin1 in gating the acquisition and persistence of cue-dependent fear conditioning. Surprisingly, we also find that depotentiation, a proposed cellular mechanism of extinction, is enhanced at lateral-basolateral (LA-BLA) amygdaloid synapses in Rin1(-/-) mice. Inhibition of a single Rin1 downstream effector pathway, the Abl tyrosine kinases, led to reduced amygdaloid depotentiation, arguing that proper coordination of Abl and Rab5 pathways is critical for Rin1-mediated effects on plasticity. While demonstrating a correlation between amygdala plasticity and fear learning, our findings argue against models proposing a direct causative relationship between amygdala depotentiation and fear extinction. Taken together, the behavior and physiology of Rin1(-/-) mice provide new insights into the regulation of memory acquisition and maintenance. In addition, Rin1(-/-) mice should prove useful as a model for pathologies marked by enhanced fear acquisition and retention, such as posttraumatic stress disorder.
de Carvalho Myskiw, Jociane; Furini, Cristiane Regina Guerino; Schmidt, Bianca; Ferreira, Flávia; Izquierdo, Ivan
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.
Gass, Justin T; Trantham-Davidson, Heather; Kassab, Amanda S; Glen, William B; Olive, M Foster; Chandler, L Judson
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.
Pace-Schott, Edward F; Verga, Patrick W; Bennett, Tobias S; Spencer, Rebecca M C
Simulated exposure therapy for spider phobia served as a clinically naturalistic model to study effects of sleep on extinction. Spider-fearing, young adult women (N = 66), instrumented for skin conductance response (SCR), heart rate acceleration (HRA) and corrugator electromyography (EMG), viewed 14 identical 1-min videos of a behaving spider before a 12-hr delay containing a normal night's Sleep (N = 20) or continuous daytime Wake (N = 23), or a 2-hr delay of continuous wake in the Morning (N = 11) or Evening (N = 12). Following the delay, all groups viewed this same video 6 times followed by six 1-min videos of a novel spider. After each video, participants rated disgust, fearfulness and unpleasantness. In all 4 groups, all measures except corrugator EMG diminished across Session 1 (extinction learning) and, excepting SCR to a sudden noise, increased from the old to novel spider in Session 2. In Wake only, summed subjective ratings and SCR to the old spider significantly increased across the delay (extinction loss) and were greater for the novel vs. the old spider when it was equally novel at the beginning of Session 1 (sensitization). In Sleep only, SCR to a sudden noise decreased across the inter-session delay (extinction augmentation) and, along with HRA, was lower to the novel spider than initially to the old spider in Session 1 (extinction generalization). None of the above differentiated Morning and Evening groups suggesting that intervening sleep, rather than time-of-testing, produced differences between Sleep and Wake. Thus, sleep following exposure therapy may promote retention and generalization of extinction learning.
Pace-Schott, Edward F.; Verga, Patrick; Bennet, Tobias; Spencer, Rebecca M.C.
Simulated exposure therapy for spider phobia served as a clinically naturalistic model to study effects of sleep on extinction. Spider-fearing, young adult women (N=66), instrumented for skin conductance response (SCR), heart rate acceleration (HRA) and corrugator electromyography (EMG), viewed 14 identical 1-min videos of a behaving spider before a 12-hr delay containing a normal night’s Sleep (N=20) or continuous daytime Wake (N=23), or a 2-hr delay of continuous wake in the Morning (N=11) or Evening (N=12). Following the delay, all groups viewed this same video 6 times followed by six 1-min videos of a novel spider. After each video, participants rated disgust, fearfulness and unpleasantness. In all 4 groups, all measures except corrugator EMG diminished across Session 1 (extinction learning) and, excepting SCR to a sudden noise, increased from the old to novel spider in Session 2. In Wake only, summed subjective ratings and SCR to the old spider significantly increased across the delay (extinction loss) and were greater for the novel vs. the old spider when it was equally novel at the beginning of Session 1 (sensitization). In Sleep only, SCR to a sudden noise decreased across the inter-session delay (extinction augmentation) and, along with HRA, was lower to the novel spider than initially to the old spider in Session 1 (extinction generalization). None of the above differentiated Morning and Evening groups suggesting that intervening sleep, rather than time-of-testing, produced differences between Sleep and Wake. Thus, sleep following exposure therapy may promote retention and generalization of extinction learning. PMID:22578824
Acheson, D.T.; Geyer, M.A.; Baker, D.G.; Nievergelt, C.M.; Yurgil, K.; Risbrough, V.B.
Summary Background Posttraumatic Stress Disorder (PTSD) is a major public health concern, especially given the recent wars in Iraq and Afghanistan. Nevertheless, despite a sharp increase in the incidence of psychiatric disorders in returning veterans, empirically based prevention strategies are still lacking. To develop effective prevention and treatment strategies, it is necessary to understand the underlying biological mechanisms contributing to PTSD and other trauma related symptoms. Methods The “Marine Resiliency Study II” (MRS-II; October 2011–October 2013) Neurocognition project is an investigation of neurocognitive performance in Marines about to be deployed to Afghanistan. As part of this investigation, 1195 Marines and Navy corpsmen underwent a fear conditioning and extinction paradigm and psychiatric symptom assessment prior to deployment. The current study assesses (1) the effectiveness of the fear potentiated startle paradigm in producing fear learning and extinction and (2) the association of performance in the paradigm with baseline psychiatric symptom classes (healthy: n = 923, PTSD symptoms: n = 42, anxiety symptoms: n = 37, and depression symptoms: n = 12). Results Results suggest that the task was effective in producing differential fear learning and fear extinction in this cohort. Further, distinct patterns emerged differentiating the PTSD and anxiety symptom classes from both healthy and depression classes. During fear acquisition, the PTSD symptom group was the only group to show deficient discrimination between the conditioned stimulus (CS+) and safety cue (CS−), exhibiting larger startle responses during the safety cue compared to the healthy group. During extinction learning, the PTSD symptom group showed significantly less reduction in their CS+ responding over time compared to the healthy group, as well as reduced extinction of self-reported anxiety to the CS+ by the end of the extinction session. Conversely, the anxiety symptom
Song, Minryung R; Fellous, Jean-Marc
Because most rewarding events are probabilistic and changing, the extinction of probabilistic rewards is important for survival. It has been proposed that the extinction of probabilistic rewards depends on arousal and the amount of learning of reward values. Midbrain dopamine neurons were suggested to play a role in both arousal and learning reward values. Despite extensive research on modeling dopaminergic activity in reward learning (e.g. temporal difference models), few studies have been done on modeling its role in arousal. Although temporal difference models capture key characteristics of dopaminergic activity during the extinction of deterministic rewards, they have been less successful at simulating the extinction of probabilistic rewards. By adding an arousal signal to a temporal difference model, we were able to simulate the extinction of probabilistic rewards and its dependence on the amount of learning. Our simulations propose that arousal allows the probability of reward to have lasting effects on the updating of reward value, which slows the extinction of low probability rewards. Using this model, we predicted that, by signaling the prediction error, dopamine determines the learned reward value that has to be extinguished during extinction and participates in regulating the size of the arousal signal that controls the learning rate. These predictions were supported by pharmacological experiments in rats.
Laurent, Vincent; Westbrook, R. Frederick
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…
Kimura, Ryoichi; Silva, Alcino J.; Ohno, Masuo
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…
Jones, Robyn L.
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…
Mills, Annie; Schmied, Virginia; Taylor, Christine; Dahlen, Hannah; Schuiringa, Wies; Hudson, Margaret E
Providing support and parenting education through home visiting is a key early intervention strategy with young parents. Less is known about what home visitors do that makes a difference. The purpose of this paper is to describe the role and experiences of professional staff working with young parents participating in a multicomponent parent support programme (home visiting and supported parenting groups) provided by a non-government organisation in a socially disadvantaged area of Sydney, Australia. This was a qualitative descriptive study. Data were collected through three focus groups conducted with the same six staff over an 18-month period. Participant descriptions of their role and experiences working with young mothers were analysed thematically. Additional data from 20 anonymised client records were analysed through content analysis. Analysis of the focus group data revealed two themes, 'Connecting' and 'Facilitating Learning'. The theme 'Connecting' reflected the development of a relationship with the young mother commencing with 'how do we engage them?', 'building trust' through to formation of a relationship described as 'they know we're not friends, they know we're workers'. The second theme, 'Facilitating Learning' was informed by the analysis of both group and client record data and comprised a number of themes around what and how mothers learnt, through to 'ending the relationship' as the mothers left the programme. The quality of a mothers' learning was dependent on the quality of the connection between herself and the staff, similarly their capacity and, or confidence to leave the programme was dependent on the relationship, 'connecting' and the learning undertaken. Role modelling through interactions with children as well as with each other was seen as the most effective way to facilitate social and parenting skill development, while formal education sessions were evaluated by the workers to be less successful than informal ones.
Awad, Walaa; Ferreira, Guillaume; Maroun, Mouna
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.
André, Susan M; Markowski, Vincent P
Vinclozolin (Vz) is one member of a group of fungicides whose metabolites are androgen receptor antagonists. These fungicides have been shown to block androgen-driven development and compromise reproductive function. The current study sought to determine if Vz also affects learning following exposure to low doses during the perinatal period. To test this, an androgen-dependent behavior was examined, the extinction of a previously reinforced running response. Pregnant Long-Evans rats were administered a daily oral dose of 0, 1.5, 3, 6 or 12 mg/kg Vz from the 14th day of gestation through postnatal day 3. After reaching adulthood, male and female offspring were trained to run through a short alleyway for food reinforcement. Acquisition of the response was not affected by Vz exposure. However, males required more trials than females for response extinction once food was no longer available in the apparatus. Males exposed to 6 or 12 mg/kg Vz failed to show any extinction by the end of the procedure, while the lowest dose of Vz appeared to facilitate extinction in both male and female offspring. These results demonstrate that endocrine disrupting antiandrogens can alter nervous system development in addition to the reproductive system.
Pallarés, M A; Nadal, R A; Hernández-Torres, M; Ferré, N A
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.
Cohen, Joshua; Gotthard, Gretchen Hanson
The present study investigated whether memory for extinction in an appetitive task (the sand maze) could be attenuated by administration of cycloheximide (protein synthesis inhibitor) or propranolol (β-adrenergic receptor antagonist). Ninety-day-old male Long-Evans rats were trained to retrieve a sweet cereal reinforcer from an open container in the sand maze. One day following this non-spatial training, rats received three extinction trials in which they were placed in the maze with the reinforcer present, but unattainable. Thirty minutes prior to the first extinction trial, rats received an intraperitoneal injection of cycloheximide (1mg/kg), propranolol (25mg/kg), or vehicle (1mg/kg distilled water). Twenty-four hours later, rats were tested in the sand maze with the reinforcer again available. Results from the test trial showed that both cycloheximide and propranolol groups found the reinforcer more quickly than controls. Two weeks later, rats were trained on a spatial version of the sand maze in which they had to search for a buried reinforcer using extramaze cues. Cycloheximide and propranolol groups learned this task significantly faster than the control group, demonstrating the long-lasting effect of cycloheximide and propranolol on the blocking of memory for extinction.
Cavallo, Joel S.; Hamilton, Brittany N.; Farley, Joseph
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
de Carvalho Myskiw, Jociane; Furini, Cristiane Regina Guerino; Schmidt, Bianca; Ferreira, Flávia; Izquierdo, Ivan
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
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.
Campus, P; Colelli, V; Orsini, C; Sarra, D; Cabib, S
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.
Torregrossa, Mary M; Taylor, Jane R
Finding effective long-lasting treatments for drug addiction has been an elusive goal. Consequently, researchers are beginning to investigate novel treatment strategies including manipulations of drug-associated memories. When environmental stimuli (cues) become associated with drug use, they become powerful motivators of continued drug use and relapse after abstinence. Reducing the strength of these cue-drug memories could decrease the number of factors that induce craving and relapse to aid in the treatment of addiction. Enhancing the consolidation of extinction learning and/or disrupting cue-drug memory reconsolidation are two strategies that have been proposed to reduce the strength of cues in motivating drug-seeking and drug-taking behavior. Here, we review the latest basic and clinical research elucidating the mechanisms underlying consolidation of extinction and reconsolidation of cue-drug memories in the hopes of developing pharmacological tools that exploit these signaling systems to treat addiction.
Topic, Bianca; Kröger, Inga; Vildirasova, Petya G; Huston, Joseph P
Loss of reward is one of the etiological factors leading to affective disorders, such as major depression. We have proposed several variants of an animal model of depression based on extinction of reinforced behavior of rats. A number of behaviors emitted during extinction trials were found to be attenuated by antidepressant treatment and, thus, qualified as indices of extinction-induced "despair". These include increases in immobility in the Morris water maze and withdrawal from the former source of reward as well as biting behavior in operant chambers. Here, we assess the effects of reward omission on behaviors after learning of (a) a cued free-reward delivery in an operant chamber and (b) food-reinforced runway behavior. Sixty adult male Wistar rats were either trained to receive food reinforcement every 90 s (s) after a 5s lasting cue light (FI 90), or to traverse an alley to gain food reward. Daily drug treatment with either the selective serotonin reuptake inhibitor citalopram or the tricyclic antidepressant imipramine (each 10mg/kg) or vehicle was begun either 25 days (operant chamber) or 3 days (runway) prior to extinction. The antidepressants suppressed rearing behavior in both paradigms specifically during the extinction trials, which indicates this measure as a useful marker of depression-related behavior, possibly indicating vertical withdrawal. In the operant chamber, only marginal effects on operant learning responses during extinction were found. In the runway, the operant learned responses run time and distance to the goal, as well as total distance moved, grooming and quiescence were also influenced by the antidepressants, providing a potential set of markers for extinction-induced "depression" in the runway. Both paradigms differ substantially with respect to the anticipation of reward, behaviors that are learned and that accompany extinction. Accordingly, antidepressant treatment influenced different sets of behaviors in these two learning tasks.
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.
Martel, Guillaume; Hevi, Charles; Friebely, Olivia; Baybutt, Trevor; Shumyatsky, Gleb P
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.
Hart, Genevra; Harris, Justin A.; Westbrook, R. Frederick
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…
Dubrovina, N I; Zinov'ev, D R; Zinov'eva, D V; Kulikov, A V
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.
This article explores the development of learning identities among 51 young New Zealanders who left school with few or no qualifications. Most experienced a period of time after leaving school when they were not in education, employment or training (known as NEET). At the time of this research all had moved into a learning environment of some…
Prados, José; Sansa, Joan; Artigas, Antonio A
In two experiments, two groups of rats were trained in a navigation task according to either a continuous or a partial schedule of reinforcement. In Experiment 1, animals that were given continuous reinforcement extinguished the spatial response of approaching the goal location more readily than animals given partial reinforcement-a partial reinforcement extinction effect. In Experiment 2, after partially or continuously reinforced training, animals were trained in a new task that made use of the same reinforcer according to a continuous reinforcement schedule. Animals initially given partial reinforcement performed better in the novel task than did rats initially given continuous reinforcement. These results replicate, in the spatial domain, well-known partial reinforcement phenomena typically observed in the context of Pavlovian and instrumental conditioning, suggesting that similar principles govern spatial and associative learning. The results reported support the notion that salience modulation processes play a key role in determining partial reinforcement effects.
Kufahl, Peter R.; Hood, Lauren E.; Nemirovsky, Natali E.; Barabas, Piroska; Halstengard, Casey; Villa, Angel; Moore, Elisabeth; Watterson, Lucas R.; Olive, M. Foster
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
Myers, Karyn M.; Davis, Michael
The neural mechanisms of fear suppression most commonly are studied through the use of extinction, a behavioral procedure in which a feared stimulus (i.e., one previously paired with shock) is nonreinforced repeatedly, leading to a reduction or elimination of the fear response. Although extinction is perhaps the most convenient index of fear inhibition, a great deal of behavioral work suggests that postextinction training conditioned stimuli are both excitatory and inhibitory, making it difficult to determine whether a neural manipulation affects inhibition, excitation, or some combination thereof. For this reason we sought to develop a behavioral procedure that would render a stimulus primarily inhibitory while at the same time avoiding some of the issues raised by the traditional conditioned inhibition paradigm, namely second-order conditioning, external inhibition, and configural learning. Using the fear-potentiated startle paradigm, we adapted an AX+, BX- training procedure in which stimuli A and X were presented simultaneously and paired with shock, and stimuli B and X were presented simultaneously in the absence of shock. In testing, high levels of fear-potentiated startle were seen in the presence of A and AX and much lower levels were seen in the presence of B and AB, as would be predicted if stimulus B were a conditioned inhibitor. We believe this method is a viable alternative to the traditional conditioned inhibition training procedure and will be useful for studying the neural mechanisms of fear inhibition. PMID:15254216
Rosenthal, M Zachary; Kutlu, Munir G
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.
Rosenthal, M. Zachary; Kutlu, Munir G.
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
Wille, Alexandra; Maurer, Verena; Piatti, Paolo; Whittle, Nigel; Rieder, Dietmar; Singewald, Nicolas; Lusser, Alexandra
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
Cacciaglia, Raffaele; Nees, Frauke; Grimm, Oliver; Ridder, Stephanie; Pohlack, Sebastian T; Diener, Slawomira J; Liebscher, Claudia; Flor, Herta
Stress exposure causes a structural reorganization in neurons of the amygdala. In particular, animal models have repeatedly shown that both acute and chronic stress induce neuronal hypertrophy and volumetric increase in the lateral and basolateral nuclei of amygdala. These effects are visible on the behavioral level, where stress enhances anxiety behaviors and provokes greater fear learning. We assessed stress and anxiety levels in a group of 18 healthy human trauma-exposed individuals (TR group) compared to 18 non-exposed matched controls (HC group), and related these measurements to amygdala volume. Traumas included unexpected adverse experiences such as vehicle accidents or sudden loss of a loved one. As a measure of aversive learning, we implemented a cued fear conditioning paradigm. Additionally, to provide a biological marker of chronic stress, we measured the sensitivity of the hypothalamus-pituitary-adrenal (HPA) axis using a dexamethasone suppression test. Compared to the HC, the TR group showed significantly higher levels of chronic stress, current stress and trait anxiety, as well as increased volume of the left amygdala. Specifically, we observed a focal enlargement in its lateral portion, in line with previous animal data. Compared to HC, the TR group also showed enhanced late acquisition of conditioned fear and deficient extinction learning, as well as salivary cortisol hypo-suppression to dexamethasone. Left amygdala volumes positively correlated with suppressed morning salivary cortisol. Our results indicate differences in trauma-exposed individuals which resemble those previously reported in animals exposed to stress and in patients with post-traumatic stress disorder and depression. These data provide new insights into the mechanisms through which traumatic stress might prompt vulnerability for psychopathology.
Wiescholleck, Valentina; Emma André, Marion Agnès; Manahan-Vaughan, Denise
The hippocampus is vulnerable to age-dependent memory decline. Multiple forms of memory depend on adequate hippocampal function. Extinction learning comprises active inhibition of no longer relevant learned information concurrent with suppression of a previously learned reaction. It is highly dependent on context, and evidence exists that it requires hippocampal activation. In this study, we addressed whether context-based extinction as well as hippocampus-dependent tasks, such as object recognition and object-place recognition, are equally affected by moderate aging. Young (7-8 week old) and older (7-8 month old) Wistar rats were used. For the extinction study, animals learned that a particular floor context indicated that they should turn into one specific arm (e.g., left) to receive a food reward. On the day after reaching the learning criterion of 80% correct choices, the floor context was changed, no reward was given and animals were expected to extinguish the learned response. Both, young and older rats managed this first extinction trial in the new context with older rats showing a faster extinction performance. One day later, animals were returned to the T-maze with the original floor context and renewal effects were assessed. In this case, only young but not older rats showed the expected renewal effect (lower extinction ratio as compared to the day before). To assess general memory abilities, animals were tested in the standard object recognition and object-place memory tasks. Evaluations were made at 5 min, 1 h and 7 day intervals. Object recognition memory was poor at short-term and intermediate time-points in older but not young rats. Object-place memory performance was unaffected at 5 min, but impaired at 1 h in older but not young rats. Both groups were impaired at 7 days. These findings support that not only aspects of general memory, but also context-dependent extinction learning, are affected by moderate aging. This may reflect less flexibility in
Archbold, Georgina E.; Dobbek, Nick; Nader, Karim
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…
Polewan, Robert J; Savala, Stephanie A; Bevins, Rick A
Interoceptive conditioning involving the nicotine stimulus likely contributes to chronic tobacco use. To better understand the nature of this interoceptive conditioning, we compared generalization during repeated extinction with generalization in a 'transfer of extinction' test using a wide range of test doses. Rats were first trained in the discriminated goal-tracking task in which nicotine (0.2 or 0.4 mg/kg), but not saline, was paired with repeated intermittent access to sucrose. Across sessions, nicotine acquired control of approach behavior directed at the location of previous sucrose deliveries. Extinction followed with eight 20-min sessions without sucrose access; extinction doses of nicotine ranged from 0.05 to 0.6 mg/kg. In rats trained with 0.4 mg/kg, the 0.1, 0.2, and 0.6 mg/kg doses evoked comparable responding across extinction sessions; substitution was only partial at 0.05 and 0.075 mg/kg (i.e. above saline controls, but less than the training dose). With the 0.2 mg/kg training dose, complete generalization was seen only at the 0.1 and 0.4 mg/kg doses. After extinction, rats were given a transfer test with their training dose. Rats trained with 0.4 mg/kg showed full transfer of extinction learning with 0.1, 0.2, and 0.6 mg/kg (i.e. responding comparable with extinction with the training dose). Partial transfer was observed at 0.075 mg/kg. With the 0.2 mg/kg nicotine dose, only 0.4 mg/kg fully generalized; 0.075, 0.1, and 0.6 mg/kg showed partial transfer. Extinction with 0.05 mg/kg dose did not show transfer to either training dose. These findings indicated that conclusions regarding stimulus similarity across nicotine doses can vary with testing protocol.
Gabriele, Amanda; Packard, Mark G
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.
HOWARTH, C I; DEUTSCH, J A
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.
Campus, P; Maiolati, M; Orsini, C; Cabib, S
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.
Myers, Karyn M.; Davis, Michael
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…
Lucantonio, Federica; Kambhampati, S; Haney, Richard Z; Atalayer, Deniz; Rowland, Neil E; Shaham, Yavin; Schoenbaum, Geoffrey
Background Addiction is characterized by an inability to stop using drugs, despite adverse consequences. One contributing factor to this compulsive drug taking could be the impact of drug use on the ability to extinguish drug seeking after changes in expected outcomes. Here we compared effects of cocaine, morphine, and heroin self-administration on two forms of extinction learning: standard extinction driven by reward omission and extinction driven by reward over-expectation. Methods In Experiment 1, we trained rats to self-administer cocaine, morphine, or sucrose for 3 hr/day (limited access). In Experiment 2, we trained rats to self-administer heroin or sucrose for 12 hr/day (extended access). Three weeks later, we trained the rats to associate several cues with palatable food reward, after which we assessed extinction of the learned Pavlovian response, first by pairing two cues together in the over-expectation procedure and later by omitting the food reward. Results Rats trained under limited access conditions to self-administer sucrose or morphine demonstrated normal extinction in response to both over-expectation and reward omission, whereas cocaine-experienced rats or rats trained to self-administer heroin under extended access conditions exhibited normal extinction in response to reward omission but failed to show extinction in response to over-expectation. Conclusions The specific long-lasting effects of cocaine and heroin show that drug exposure induces long-lasting deficits in the ability to extinguish reward seeking after changes in expected outcomes. These deficits were not observed in a standard extinction procedure but instead only affected extinction learning driven by a more complex phenomenon of over-expectation. PMID:25641634
Thompson, Brittany M.; Baratta, Michael V.; Biedenkapp, Joseph C.; Rudy, Jerry W.; Watkins, Linda R.; Maier, Steven F.
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…
Olatunji, Bunmi O; Forsyth, John P; Cherian, Ancy
The present study sought to (a) test whether autonomic (i.e., electrodermal) and evaluative conditioning can be differentially established to verbal CSs, and (b) whether extinction procedures can reliably attenuate differential conditioned evaluative responding. Thirty undergraduates underwent a 10-min adaptation period followed by three consecutive conditioning phases: habituation, acquisition, and extinction. Conditioning involved participants viewing two semi-randomly presented words on a computer monitor. During acquisition, one word (CS+) was reliably paired 12 times with the UCS (pictorial stimuli depicting bodily mutilation), whereas the remaining word (CS-) was presented 12 times and reliably followed by neutral pictures (inanimate common objects). As predicted, electrodermal and evaluative responses during acquisition were of larger magnitude to the CS+ compared to the CS-. During extinction, participants continued to evaluate the CS+ as more disgusting relative to the CS-, whereas distress and fear-related emotional ratings attenuated across extinction trials. The implications of these findings for the modifiability of disgust-based evaluative responses in specific anxiety disorders will be discussed.
Diaz, Estrella; De la Casa, L. G.
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…
Sturman, David A; Mandell, Daniel R; Moghaddam, Bita
Adolescence is associated with the development of brain regions linked to cognition and emotion. Such changes are thought to contribute to the behavioral and neuropsychiatric vulnerabilities of this period. We compared adolescent (Postnatal Days 28-42) and adult (Postnatal Day 60+) rats as they performed a simple instrumental task and extinction. Rats were trained to poke into a hole for a food-pellet reinforcer. After six days of training, rats underwent extinction sessions in which the previously rewarded behavior was no longer reinforced. During extinction, we examined the effects of continued presentation of a cue light and food restriction. Adults and adolescents exhibited similar performance during training, although adolescents made more task-irrelevant pokes, consistent with increased exploration. Adults made more premature pokes, which could indicate a more exclusive focus on the task. During extinction, adolescents made more perseverative (previously reinforced) pokes than adults. This behavior was strongly modulated by the combination of motivational factors present (food restriction and cue light), indicating that adolescents were differentially sensitive to them. Furthermore, food restriction induced greater open-field activity in adolescents but not in adults. Thus, as the neural circuitry of motivated behavior develops substantially during adolescence, so too does the behavioral sensitivity to motivational factors. Understanding how such factors differently affect adolescents may shed light on mechanisms that lead to the development of disorders that are manifested during this period.
André, Marion Agnes Emma; Güntürkün, Onur; Manahan-Vaughan, Denise
The metabotropic glutamate (mGlu) receptors and, in particular, mGlu5 are crucially involved in multiple forms of synaptic plasticity that are believed to underlie explicit memory. MGlu5 is also required for information transfer through neuronal oscillations and for spatial memory. Furthermore, mGlu5 is involved in extinction of implicit forms of learning. This places this receptor in a unique position with regard to information encoding. Here, we explored the role of this receptor in context-dependent extinction learning under constant, or changed, contextual conditions. Animals were trained over 3 days to take a left turn under 25% reward probability in a T-maze with a distinct floor pattern (Context A). On Day 4, they experienced either a floor pattern change (Context B) or the same floor pattern (Context A) in the absence of reward. After acquisition of the task, the animals were returned to the maze once more on Day 5 (Context A, no reward). Treatment with the mGlu5 antagonist, 2-methyl-6-(phenylethynyl) pyridine, before maze exposure on Day 4 completely inhibited extinction learning in the AAA paradigm but had no effect in the ABA paradigm. A subsequent return to the original context (A, on Day 5) revealed successful extinction in the AAA paradigm, but impairment of extinction in the ABA paradigm. These data support that although extinction learning in a new context is unaffected by mGlu5 antagonism, extinction of the consolidated context is impaired. This suggests that mGlu5 is intrinsically involved in enabling learning that once-relevant information is no longer valid. © 2014 The Authors. Hippocampus Published by Wiley Periodicals, Inc. PMID:25160592
André, Marion Agnes Emma; Güntürkün, Onur; Manahan-Vaughan, Denise
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.
Knackstedt, Lori A; Schwendt, Marek
We have previously demonstrated that MTEP, an allosteric antagonist of mGlu5, infused into the nucleus accumbens attenuates relapse after abstinence from cocaine self-administration. MTEP infused into the dorsolateral striatum (dlSTR) does not alter relapse but has long-lasting effects on subsequent extinction learning. Here we tested whether systemic MTEP would prevent relapse after abstinence or alter extinction learning. We also investigated the mechanism of action by which intra-dlSTR MTEP on test day alters extinction on subsequent days. Animals self-administered cocaine for 12 days followed by abstinence for 20-21 days. MTEP (0.5-5 mg/kg IP) was administered prior to placement into the operant chamber for a context-primed relapse test. A separate group of animals received intra-dlSTR MTEP prior to the relapse test and were sacrificed day later. Systemic administration of MTEP attenuated abstinent-relapse without significantly affecting extinction learning. Surface biotinylation analysis of protein expression in the dlSTR revealed that, in cocaine animals, intra-dlSTR MTEP administration decreased mGlu5 surface expression and prevented changes in Arc and GluA1/GluA2 observed in their vehicle counterparts. Thus, blockade of mGlu5 receptors may be utilized in future treatment strategies for relapse prevention in humans, although the effects of chronic blockade on extinction learning should be further evaluated.
Van den Bergh, Filip; Spronk, Marjolein; Ferreira, Leila; Bloemarts, Emilie; Groenink, Lucianne; Olivier, Berend; Oosting, Ronald
Impulsivity is an important symptom of many psychiatric disorders, and can be divided into two subtypes: response inhibition deficits and delay aversion. In the present study, we investigated the relationship between delay aversion and response inhibition, both to each other and to locomotion, extinction of conditioned responses, sexual behaviour, and aggressive behaviour. To that end, we quantified the behaviour of 24 rats in several tests. To measure response inhibition, rats were trained in a stop-signal task. In this operant task, rats were rewarded food if they inhibited execution of a response after presentation of an audible stop-signal. Delay aversion was measured in an operant task in which rats made a choice between a small, immediately available reward and a large reward available after a delay. The results showed that delay aversion and response inhibition were independent. Responses during extinction and various measures of aggressive behaviour were positively correlated to delay aversion. The speed of go-trials in the stop-task was correlated to non-aggressive behaviour. We conclude that the role of response inhibition in various behaviours is small, but delay aversion in particular contributes to several other behaviours, such as aggressive behaviour and extinction.
Nachtigall, Paul E; Supin, Alexander Ya; Estaban, Jose-Antonio; Pacini, Aude F
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.
Asnaani, Anu; McLean, Carmen P; Foa, Edna B
J. P. Watson and I. M. Marks published a seminal article in Behavior Therapy entitled "Relevant and Irrelevant Fear in Flooding-A Crossover Study of Phobic Patients" in 1971 that paved the way for important theoretical developments and empirical studies that examined the mechanisms underlying extinction learning. Indeed, in the 44 years since their article was published, our knowledge about how exposure therapy works has increased considerably. In this review, we explore the progress our field has made in understanding extinction learning and how Watson and Marks' important work has influenced this progress. We provide a brief summary of the design and major findings of the Watson and Marks (1971) study, followed by a brief description of several theoretical conceptualizations of fear extinction that were developed following the article's publication. We also review empirical studies that illustrate the "state of the science" with regard to the following key issues that were explored in Watson and Marks' paper: (a) the effect of specificity of exposure stimuli content in exposure therapy on outcome; (b) fear activation as a mechanism of exposure; and (c) the associations between within- and between-session extinction learning and treatment outcome. The major findings of these three issues over the past 4 decades are summarized and discussed.
Herry, Cyril; Ferraguti, Francesco; Singewald, Nicolas; Letzkus, Johannes J; Ehrlich, Ingrid; Lüthi, Andreas
Fear extinction is a form of inhibitory learning that allows for the adaptive control of conditioned fear responses. Although fear extinction is an active learning process that eventually leads to the formation of a consolidated extinction memory, it is a fragile behavioural state. Fear responses can recover spontaneously or subsequent to environmental influences, such as context changes or stress. Understanding the neuronal substrates of fear extinction is of tremendous clinical relevance, as extinction is the cornerstone of psychological therapy of several anxiety disorders and because the relapse of maladaptative fear and anxiety is a major clinical problem. Recent research has begun to shed light on the molecular and cellular processes underlying fear extinction. In particular, the acquisition, consolidation and expression of extinction memories are thought to be mediated by highly specific neuronal circuits embedded in a large-scale brain network including the amygdala, prefrontal cortex, hippocampus and brain stem. Moreover, recent findings indicate that the neuronal circuitry of extinction is developmentally regulated. Here, we review emerging concepts of the neuronal circuitry of fear extinction, and highlight novel findings suggesting that the fragile phenomenon of extinction can be converted into a permanent erasure of fear memories. Finally, we discuss how research on genetic animal models of impaired extinction can further our understanding of the molecular and genetic bases of human anxiety disorders.
Sharma, Ajitha; Shetty, Manjunath; Parida, Amrita; Adiga, Shalini; Kamath, Shobha; Sowjanya
Background: The effects and benefits of Acacia auriculiformis on health are not well established. This study was planned to evaluate the effect of ethanolic extract of Acacia auriculiformis leaves on learning and memory in rats. Materials and Methods: Learning and memory were evaluated using passive avoidance paradigm and rewarded alternation test (T-maze) after the oral administration of two doses (200mg/kg and 400mg/kg) of ethanolic extract of Acacia auriculiformis with rivastigmine as positive control. Forty eight rats were divided into 4 groups in each study model. Estimation of brain cholinesterase activity was done to substantiate the results of the above mentioned tests. Data was analyzed using one way Analysis of Variance (ANOVA) followed by Tukey's post-hoc test using GraphPad InStat software, version 3.06. Results: The extract produced a dose-dependent improvement in the memory score namely the step through latency in passive avoidance model (P < 0.001) and the percentage of correct responses in rewarded alternation test (P < 0.05). Dose-dependent inhibition of brain cholinesterase activity (P < 0.001) was also noted. Conclusion: The acetylcholinesterase inhibiting property of Acacia auriculiformis contributes to its memory enhancing potential. Further large scale studies are required to elucidate its benefits on cognitive function. This may offer a promising new option for the treatment of dementia and other cognitive deficits. PMID:25002806
Knackstedt, Lori A; Trantham-Davidson, Heather L; Schwendt, Marek
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.
Lingawi, Nura W; Westbrook, R Fredrick; Laurent, Vincent
Extinction and latent inhibition each refer to a reduction in conditioned responding: the former occurs when pairings of a conditioned stimulus (CS) and an unconditioned stimulus (US) are followed by repeated presentations of the CS alone; the latter occurs when CS alone presentations precede its pairings with the US. The present experiments used fear conditioning to test the hypothesis that both phenomena involve a similar form of inhibitory learning that recruits common neuronal substrates. We found that the initial inhibitory memory established by extinction is reactivated in the infralimbic (IL) cortex during additional extinction. Remarkably, this reactivation also occurs when the initial inhibitory memory had been established by latent inhibition. In both cases, the inhibitory memory was strengthened by pharmacological stimulation of the IL. Moreover, NMDA receptor blockade in the IL disrupted the weakening in conditioned responding produced by either latent inhibition or extinction. These findings, therefore, indicate that latent inhibition and extinction produce a similar inhibitory memory that is retrieved from the IL. They also demonstrate that the IL plays a wide role in fear regulation by promoting the retrieval of inhibitory memories generated by CS alone presentations either before or after this CS has been rendered dangerous.
André, Marion Agnès Emma; Wolf, Oliver T.; Manahan-Vaughan, Denise
The noradrenergic (NA)-system is an important regulator of cognitive function. It contributes to extinction learning (EL), and in disorders where EL is impaired NA-dysfunction has been postulated. We explored whether NA acting on beta-adrenergic-receptors (β-AR), regulates EL that depends on context, but is not fear-associated. We assessed behavior in an “AAA” or “ABA” paradigm: rats were trained for 3 days in a T-maze (context-A) to learn that a reward is consistently found in the goal arm, despite low reward probability. This was followed on day 4 by EL (unrewarded), whereby in the ABA-paradigm, EL was reinforced by a context change (B), and in the AAA-paradigm, no context change occurred. On day 5, re-exposure to the A-context (unrewarded) occurred. Typically, in control “AAA” animals EL occurred on day 4 that progressed further on day 5. In control “ABA” animals, EL also occurred on day 4, followed by renewal of the previously learned (A) behavior on day 5, that was succeeded (on day 5) by extinction of this behavior, as the animals realised that no food reward would be given. Treatment with the β-AR-antagonist, propranolol, prior to EL on day 4, impaired EL in the AAA-paradigm. In the “ABA” paradigm, antagonist treatment on day 4, had no effect on extinction that was reinforced by a context change (B). Furthermore, β-AR-antagonism prior to renewal testing (on day 5) in the ABA-paradigm, resulted in normal renewal behavior, although subsequent extinction of responses during day 5 was prevented by the antagonist. Thus, under both treatment conditions, β-AR-antagonism prevented extinction of the behavior learned in the “A” context. β-AR-blockade during an overt context change did not prevent EL, whereas β-AR were required for EL in an unchanging context. These data suggest that β-AR may support EL by reinforcing attention towards relevant changes in the previously learned experience, and that this process supports extinction
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…
Labrie, Viviane; Duffy, Steven; Wang, Wei; Barger, Steven W.; Baker, Glen B.; Roder, John C.
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…
Martel, Guillaume; Hevi, Charles; Friebely, Olivia; Baybutt, Trevor; Shumyatsky, Gleb P.
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,…
Skelly, M J; Chappell, A M; Ariwodola, O J; Weiner, J L
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.
Nair, Satish S.; Paré, Denis; Vicentic, Aleksandra
The neuronal systems that promote protective defensive behaviours have been studied extensively using Pavlovian conditioning. In this paradigm, an initially neutral-conditioned stimulus is paired with an aversive unconditioned stimulus leading the subjects to display behavioural signs of fear. Decades of research into the neural bases of this simple behavioural paradigm uncovered that the amygdala, a complex structure comprised of several interconnected nuclei, is an essential part of the neural circuits required for the acquisition, consolidation and expression of fear memory. However, emerging evidence from the confluence of electrophysiological, tract tracing, imaging, molecular, optogenetic and chemogenetic methodologies, reveals that fear learning is mediated by multiple connections between several amygdala nuclei and their distributed targets, dynamical changes in plasticity in local circuit elements as well as neuromodulatory mechanisms that promote synaptic plasticity. To uncover these complex relations and analyse multi-modal data sets acquired from these studies, we argue that biologically realistic computational modelling, in conjunction with experiments, offers an opportunity to advance our understanding of the neural circuit mechanisms of fear learning and to address how their dysfunction may lead to maladaptive fear responses in mental disorders.
Hugues, Sandrine; Garcia, Rene
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…
Bustamante, Javier; Uengoer, Metin; Thorwart, Anna; Lachnit, Harald
In two human predictive-learning experiments, we investigated the effects of extinction in multiple contexts on the rate of extinction and the strength of response recovery. In each experiment, participants initially received acquisition training with a target cue in one context, followed by extinction either in a different context (extinction in a single context) or in three different contexts (extinction in multiple contexts). The results of both experiments showed that conducting extinction in multiple contexts led to higher levels of responding during extinction than did extinction in a single context. Additionally, Experiment 2 showed that extinction in multiple contexts prevented ABC renewal but had no detectable impact on ABA renewal. Our results are discussed within the framework of contemporary learning theories of contextual control and extinction.
McConnell, Bridget L; Miguez, Gonzalo; Miller, Ralph R
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.
Kamprath, Kornelia; Wotjak, Carsten T
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.
Wang, Zhenshan; Phan, Trongha; Storm, Daniel R
Although primary cilia are found on neurons throughout the brain, their physiological function remains elusive. Human ciliopathies are associated with cognition defects, and transgenic mice lacking proteins expressed in primary cilia exhibit defects in learning and memory. Recently, it was reported that mice lacking the G-protein-coupling receptor somatostatin receptor-3 (SSTR3), a protein expressed predominately in the primary cilia of neurons, have defective memory for novel object recognition and lower cAMP levels in the brain. Since SSTR3 is coupled to regulation of adenylyl cyclase, this suggests that adenylyl cyclase activity in primary cilia of CNS neurons may be critical for some forms of learning and memory. Because the type 3 adenylyl cyclase (AC3) is expressed in primary cilia of hippocampal neurons, we examined AC3(-/-) mice for several forms of learning and memory. Here, we report that AC3(-/-) mice show no short-term memory for novel objects and fail to exhibit extinction of contextual fear conditioning. They also show impaired learning and memory for temporally dissociative passive avoidance. Since AC3 is exclusively expressed in primary cilia, we conclude that cAMP signals generated within primary cilia contribute to some forms of learning and memory, including extinction of contextual fear conditioning.
Lattal, K Matthew; Lattal, Kennon A
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.
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.
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
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.
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…
Hovdhaugen, Elisabeth; Aamodt, Per Olaf
This paper presents an analysis of the reasons why students in Norway leave higher education institutions before degree completion and the extent to which these reasons are of the type that can be influenced by the university. As occurs in many countries, a proportion of students starting an undergraduate liberal arts degree in Norway leave their…
Ohman, A; Eriksson, A; Olofsson, C
Human subjects were exposed to pictures of potentially phobic (snakes) and supposedly neutral (houses) objects as conditioned stimuli (CSs) in a Pavlovian conditioning experiment with shock as unconditioned stimulus (US), and skin conductance and finger pulse volume as dependent variables. The skin conductance responses conditioned to phobic stimuli were acquired after one CS-US pairing, and showed practically no extinction, whereas the responses to neutral stimuli showed very little resistance to extinction after both 1 and 5 reinforcements. The superior resistance to extinction of the phobic condition was interpreted to be a specific associative effect. In general, the skin conductance acquisition data showed tendencies similar to those during extinction. For finger pulse volume responses, however, there were very weak conditioning effects, and no effect of stimulus.
Toledo-Rodriguez, Maria; Pitiot, Alain; Paus, Tomáš; Sandi, Carmen
Adolescence is characterized by major developmental changes that may render the individual vulnerable to stress and the development of psychopathologies in a sex-specific manner. Earlier we reported lower anxiety-like behavior and higher risk-taking and novelty seeking in rats previously exposed to peri-pubertal stress. Here we studied whether peri-pubertal stress affected the acquisition and extinction of fear memories and/or the associated functional engagement of various brain regions, as assessed with 2-deoxyglucose. We showed that while peri-pubertal stress reduced freezing during the acquisition of fear memories (training) in both sexes, it had a sex-specific effect on extinction of these memories. Moreover hippocampus, basal amygdala and cingulate and motor cortices showed higher metabolic rates during extinction in rats exposed to peri-pubertal stress. Interestingly, activation of the infralimbic cortex was negatively correlated with freezing during extinction only in control males, while only males stressed during puberty showed a significant correlation between behavior during extinction and metabolic activation of hippocampus, amygdala and paraventricular nucleus. No correlations between brain activation and behavior during extinction were observed in females (control or stress). These results indicate that exposure to peri-pubertal stress affects behavior and brain metabolism when the individual is exposed to an additional stressful challenge. Some of these effects are sex-specific.
Karam, M. A.; Fung, A. K.; Blanchard, A. J.; Nance, C. E.
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.
Maren, Stephen; Holmes, Andrew
Stress has a critical role in the development and expression of many psychiatric disorders, and is a defining feature of posttraumatic stress disorder (PTSD). Stress also limits the efficacy of behavioral therapies aimed at limiting pathological fear, such as exposure therapy. Here we examine emerging evidence that stress impairs recovery from trauma by impairing fear extinction, a form of learning thought to underlie the suppression of trauma-related fear memories. We describe the major structural and functional abnormalities in brain regions that are particularly vulnerable to stress, including the amygdala, prefrontal cortex, and hippocampus, which may underlie stress-induced impairments in extinction. We also discuss some of the stress-induced neurochemical and molecular alterations in these brain regions that are associated with extinction deficits, and the potential for targeting these changes to prevent or reverse impaired extinction. A better understanding of the neurobiological basis of stress effects on extinction promises to yield novel approaches to improving therapeutic outcomes for PTSD and other anxiety and trauma-related disorders. PMID:26105142
Sepkoski, J. J. Jr; Sepkoski JJ, J. r. (Principal Investigator)
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.
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 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 . 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
Bouton, Mark E.
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…
Science Teacher, 2005
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…
Woods, Amanda M.; Bouton, Mark E.
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…
Karam, M. A.; Fung, A. K.
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.
Delamater, Andrew R; Westbrook, R Frederick
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).
This paper is a story of personal learning. I locate its beginning in my early, comfortable adoption of liberalism as the preferred perspective for my work as a philosopher of education. I then trace how and why I became disaffected with this perspective. I describe how learning from students, feminism and critical race theory led to an acceptance…
Münch, Daniel; Baker, Nicholas; Kreibich, Claus D.; Bråten, Anders T.; Amdam, Gro V.
Loss of brain function is one of the most negative and feared aspects of aging. Studies of invertebrates have taught us much about the physiology of aging and how this progression may be slowed. Yet, how aging affects complex brain functions, e.g., the ability to acquire new memory when previous experience is no longer valid, is an almost exclusive question of studies in humans and mammalian models. In these systems, age related cognitive disorders are assessed through composite paradigms that test different performance tasks in the same individual. Such studies could demonstrate that afflicted individuals show the loss of several and often-diverse memory faculties, and that performance usually varies more between aged individuals, as compared to conspecifics from younger groups. No comparable composite surveying approaches are established yet for invertebrate models in aging research. Here we test whether an insect can share patterns of decline similar to those that are commonly observed during mammalian brain aging. Using honey bees, we combine restrained learning with free-flight assays. We demonstrate that reduced olfactory learning performance correlates with a reduced ability to extinguish the spatial memory of an abandoned nest location (spatial memory extinction). Adding to this, we show that learning performance is more variable in old honey bees. Taken together, our findings point to generic features of brain aging and provide the prerequisites to model individual aspects of learning dysfunction with insect models. PMID:20976061
Gontcharov, G. A.
This review describes our current understanding of interstellar extinction. This differ substantially from the ideas of the 20th century. With infrared surveys of hundreds of millions of stars over the entire sky, such as 2MASS, SPITZER-IRAC, and WISE, we have looked at the densest and most rarefied regions of the interstellar medium at distances of a few kpc from the Sun. Observations at infrared and microwave wavelengths, where the bulk of the interstellar dust absorbs and radiates, have brought us closer to an understanding of the distribution of the dust particles on scales of the Galaxy and the universe. We are in the midst of a scientific revolution in our understanding of the interstellar medium and dust. Progress in, and the key results of, this revolution are still difficult to predict. Nevertheless, (a) a physically justified model has been developed for the spatial distribution of absorbing material over the nearest few kiloparsecs, including the Gould belt as a dust container, which gives an accurate estimate of the extinction for any object just by its galactic coordinates. It is also clear that (b) the interstellar medium contains roughly half the mass of matter in the galactic vicinity of the solar system (the other half is made up of stars, their remnants, and dark matter) and (c) the interstellar medium and, especially, dust, differ substantially in different regions of space and deep space cannot be understood by only studying near space.
Cockell, Charles S.
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.
Foley, Annette; Grace, Lauri
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…
Rosas, Juan M.; Paredes-Olay, Maria C.; Garcia-Gutierrez, Ana; Espinosa, Juan J.; Abad, Maria J. F.
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…
Shao, Zhifei; Er, Meng Joo; Wang, Ning
It is well known that the architecture of the extreme learning machine (ELM) significantly affects its performance and how to determine a suitable set of hidden neurons is recognized as a key issue to some extent. The leave-one-out cross-validation (LOO-CV) is usually used to select a model with good generalization performance among potential candidates. The primary reason for using the LOO-CV is that it is unbiased and reliable as long as similar distribution exists in the training and testing data. However, the LOO-CV has rarely been implemented in practice because of its notorious slow execution speed. In this paper, an efficient LOO-CV formula and an efficient LOO-CV-based ELM (ELOO-ELM) algorithm are proposed. The proposed ELOO-ELM algorithm can achieve fast learning speed similar to the original ELM without compromising the reliability feature of the LOO-CV. Furthermore, minimal user intervention is required for the ELOO-ELM, thus it can be easily adopted by nonexperts and implemented in automation processes. Experimentation studies on benchmark datasets demonstrate that the proposed ELOO-ELM algorithm can achieve good generalization with limited user intervention while retaining the efficiency feature.
Graf, Heiko; Metzger, Coraline D; Walter, Martin; Abler, Birgit
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.
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
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
Baker, Tyson W; Weisman, Ronald G; Beninger, Richard J
A common feature of reinforcer devaluation studies is that new learning induces the devaluation. The present study used extinction to induce new learning about the conditioned reinforcer in a heterogeneous chain schedule. Rats pressed a lever in a heterogeneous chain schedule to produce a conditioned reinforcer (light) associated with the opportunity to obtain an unconditioned reinforcer (food) by pulling a chain. The density of food reinforcement correlated with the conditioned reinforcer was varied in a comparison of continuous and variable-ratio reinforcement schedules of chain pulling; this had no noticeable effect on conditioned reinforcer devaluation produced by extinction of chain pulling. In contrast, how rats were deprived appeared to matter very much. Restricting meal duration to 1h daily produced more lever pressing during baseline training and a greater reductive effect of devaluation on lever pressing than restricting body weight to 80% of a control rat's weight, which eliminated the devaluation effect. Further analysis suggested that meal-duration restriction may have produced devaluation effects because it was more effective than weight restriction in reducing rats' body weights. Our results exposed an important limitation on the devaluation of conditioned reinforcers: slight differences in food restriction, using two commonly employed food-restriction procedures, can produce completely different interpretations of reinforcer devaluation while leaving reinforcer-based learning intact.
Graham, Bronwyn M.; Richardson, Rick
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,…
Frick, Luciana Romina; Bernardez-Vidal, Micaela; Hocht, Christian; Zanutto, Bonifacio Silvano; Rapanelli, Maximiliano
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.
Nelson, James Byron; Gregory, Pamela; Sanjuan, Maria del Carmen
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
Bouton, Mark E
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.
Myskiw, Jociane C; Fiorenza, Natalia G; Izquierdo, Luciana A; Izquierdo, Ivan
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.
Bai, John Y H; Podlesnik, Christopher A
Greater rates of intermittent reinforcement in the presence of discriminative stimuli generally produce greater resistance to extinction, consistent with predictions of behavioral momentum theory. Other studies reveal more rapid extinction with higher rates of reinforcers - the partial reinforcement extinction effect. Further, repeated extinction often produces more rapid decreases in operant responding due to learning a discrimination between training and extinction contingencies. The present study examined extinction repeatedly with training with different rates of intermittent reinforcement in a multiple schedule. We assessed whether repeated extinction would reverse the pattern of greater resistance to extinction with greater reinforcer rates. Counter to this prediction, resistance to extinction was consistently greater across twelve assessments of training followed by six successive sessions of extinction. Moreover, patterns of responding during extinction resembled those observed during satiation tests, which should not alter discrimination processes with repeated testing. These findings join others suggesting operant responding in extinction can be durable across repeated tests.
Janak, Patricia H.; Corbit, Laura H.
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…
Bonini, Juliana Sartori; Da Silva, Weber Cláudio; Da Silveira, Clarice Kras Borges; Köhler, Cristiano André; Izquierdo, Iván; Cammarota, Martín
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.
Robleto, Karla; Thompson, Richard F
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.
Zuzina, A B; Balaban, P M
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
The phenomenon of species extinction raises more and more concern among ecologists facing the actual crisis of biodiversity. Scientific investigations of the causes and effects of extinction must be completed by a philosophical analysis of the concept of extinction that aims to clarify the meanings of the term 'extinction' and to analyse modalities, criteria and degrees of extinction. We will focus our attention on the apparent paradox of the possible 'resurrection' of species in the near future with the help of genetic biotechnology and cloning techniques. The ontological background of the extinction concept is analysed in relation to the idea of species as classes. We will also show that there is no simple analogy between death and species extinction, and develop a conceptualist and dualistic system of supra-individual entities (species vs. population), supported by an instrumentalist approach to genetic manipulations which transform species into interactive kinds, which can go extinct and be recreated.
Pace-Schott, Edward F.; Germain, Anne; Milad, Mohammed R.
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
Antov, Martin I; Melicherová, Ursula; Stockhorst, Ursula
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.
Bridge, Eli S.; Crawford, Priscilla H. C.; Hough, Daniel J.; Kelly, Jeffrey F.; Patten, Michael A.
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
LaLumiere, Ryan T.; Niehoff, Kate E.; Kalivas, Peter W.
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…
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
Rabinak, Christine A; Angstadt, Mike; Sripada, Chandra S; Abelson, James L; Liberzon, Israel; Milad, Mohammed R; Phan, K Luan
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'.
Burtle, Adam; Bezruchka, Stephen
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
Peters, Jamie; Dieppa-Perea, Laura M; Melendez, Loyda M; Quirk, Gregory J
The extinction of conditioned fear memories requires plasticity in the infralimbic medial prefrontal cortex (IL mPFC), but little is known about the molecular mechanisms involved. Brain-derived neurotrophic factor (BDNF) is a key mediator of synaptic plasticity in multiple brain areas. In rats subjected to auditory fear conditioning, BDNF infused into the IL mPFC reduced conditioned fear for up to 48 hours, even in the absence of extinction training, which suggests that BDNF substituted for extinction. Similar to extinction, BDNF-induced reduction in fear required N-methyl-D-aspartate receptors and did not erase the original fear memory. Rats failing to learn extinction showed reduced BDNF in hippocampal inputs to the IL mPFC, and augmenting BDNF in this pathway prevented extinction failure. Hence, boosting BDNF activity in hippocampal-infralimbic circuits may ameliorate disorders of learned fear.
Brodie, Jedediah F; Aslan, Clare E; Rogers, Haldre S; Redford, Kent H; Maron, John L; Bronstein, Judith L; Groves, Craig R
Extinctions beget further extinctions when species lose obligate mutualists, predators, prey, or hosts. Here, we develop a conceptual model of species and community attributes affecting secondary extinction likelihood, incorporating mechanisms that buffer organisms against partner loss. Specialized interactors, including 'cryptic specialists' with diverse but nonredundant partner assemblages, incur elevated risk. Risk is also higher for species that cannot either evolve new traits following partner loss or obtain novel partners in communities reorganizing under changing environmental conditions. Partner loss occurs alongside other anthropogenic impacts; multiple stressors can circumvent ecological buffers, enhancing secondary extinction risk. Stressors can also offset each other, reducing secondary extinction risk, a hitherto unappreciated phenomenon. This synthesis suggests improved conservation planning tactics and critical directions for research on secondary extinctions.
Plotnick, Roy E; Smith, Felisa A; Lyons, S Kathleen
Comparing the magnitude of the current biodiversity crisis with those in the fossil record is difficult without an understanding of differential preservation. Integrating data from palaeontological databases with information on IUCN status, ecology and life history characteristics of contemporary mammals, we demonstrate that only a small and biased fraction of threatened species (< 9%) have a fossil record, compared with 20% of non-threatened species. We find strong taphonomic biases related to body size and geographic range. Modern species with a fossil record tend to be large and widespread and were described in the 19(th) century. The expected magnitude of the current extinction based only on species with a fossil record is about half of that of one based on all modern species; values for genera are similar. The record of ancient extinctions may be similarly biased, with many species having originated and gone extinct without leaving a tangible record.
Shiban, Youssef; Wittmann, Jasmin; Weißinger, Mara; Mühlberger, Andreas
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
Raup, D M
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.
Raup, D. M.
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.
Baker, Kathryn D; Den, Miriam L; Graham, Bronwyn M; Richardson, Rick
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.
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
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.
Thrailkill, Eric A; Bouton, Mark E
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.
Myers, Karyn M; Davis, Michael
The neural mechanisms by which fear is inhibited are poorly understood at the present time. Behaviorally, a conditioned fear response may be reduced in intensity through a number of means. Among the simplest of these is extinction, a form of learning characterized by a decrease in the amplitude and frequency of a conditioned response when the conditioned stimulus that elicits it is repeatedly nonreinforced. Because clinical interventions for patients suffering from fear dysregulation seek to inhibit abnormal, presumably learned fear responses, an understanding of fear extinction is likely to inform and increase the efficacy of these forms of treatment. This review considers the behavioral, cellular, and molecular literatures on extinction and presents the most recent advances in our understanding while identifying issues that require considerable further research.
Barad, Mark; Cain, Christopher K.; Blouin, Ashley M.
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…
Tonn, Bruce Edward
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.
Sepkoski, J. J. Jr; Sepkoski JJ, ,. J. r. (Principal Investigator)
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.
Doran, N.A.; Arnold, A.J.; Parker, W.C.; Huffer, F.W.
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).
Rescorla, Robert A
The effect of the presence of a conditioned inhibitor on extinction of excitatory conditioning was studied in one magazine approach and three autoshaping experiments using rats and pigeons. In each case, the presence of an inhibitor reduced responding to an exciter during extinction but allowed substantial recovery of responding to that exciter when subsequently tested separately. Control stimuli with a history of being irrelevant to reinforcement or being nonreinforced had less of a protective effect. This constitutes a clear demonstration of protection from extinction, a phenomenon of substantial theoretical and applied importance.
Dubrovina, N I
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.
Nelson, James Byron; Lombas, Sebastián; Léon, Samuel P
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).
Lee, Hongjoo J.; Haberman, Rebecca P.; Roquet, Rheall F.; Monfils, Marie-H.
Pairing a previously neutral conditioned stimulus (CS; e.g., a tone) to an aversive unconditioned stimulus (US; e.g., a footshock) leads to associative learning such that the tone alone comes to elicit a conditioned response (e.g., freezing). We have previously shown that an extinction session that occurs within the reconsolidation window (termed retrieval + extinction) attenuates fear responding and prevents the return of fear in Pavlovian fear conditioning (Monfils et al., 2009). To date, the mechanisms that explain the different behavioral outcomes between standard extinction and retrieval + extinction remain poorly understood. Here we sought to examine the differential temporal engagement of specific neural systems by these two approaches using Arc catFISH (cellular compartment analysis of temporal activity using fluorescence in situ hybridization (FISH)). Our results demonstrate that extinction and retrieval + extinction lead to differential patterns of expression, suggesting that they engage different networks. These findings provide insight into the neural mechanisms that allow extinction during reconsolidation to prevent the return of fear in rodents. PMID:26834596
Vervliet, Bram; Craske, Michelle G; Hermans, Dirk
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.
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.
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…
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…
Raio, Candace M; Brignoni-Perez, Edith; Goldman, Rachel; Phelps, Elizabeth A
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
LaLumiere, Ryan T; Niehoff, Kate E; Kalivas, Peter W
The infralimbic cortex (IL) regulates the consolidation of extinction learning for fear conditioning. Whether the IL influences the consolidation of extinction learning for cocaine self-administration is unknown. To address this issue, male Sprague-Dawley rats underwent 2 wk of cocaine self-administration followed by extinction training. On the first 5 d of extinction, rats underwent brief (15- or 30-min) extinction sessions and received intra-IL microinjections immediately after each extinction session. On days 6-12 of extinction, rats underwent full-length (2-h) extinction sessions that were used to assess the retention of the extinction learning from the short sessions. IL inactivation via microinjections of the GABA agonists baclofen and muscimol (BM) immediately after the extinction sessions (days 1-5) impaired the retention of extinction learning. Control experiments demonstrated that this effect was not due to inactivation of the prelimbic cortex or due to effects of the drugs on the subsequent day's behavior. In contrast, post-training intra-IL microinjections of the allosteric AMPA receptor potentiator 4-[2-(phenylsulfonylamino)ethylthio]-2,6-difluorophenoxyacetamide (PEPA) enhanced retention of the extinction learning. As evidence suggests a role for the beta-adrenergic receptors in memory consolidation, other rats received microinjections of the beta(2)-adrenergic receptor agonist clenbuterol or antagonist ICI-118,551 (ICI). Post-training intra-IL administration of clenbuterol or pre-training administration of ICI enhanced or impaired, respectively, the retention of extinction learning. These data indicate that the IL, and specifically the glutamatergic and beta-adrenergic systems in the IL, regulates the consolidation of extinction of cocaine self-administration and that the IL can be manipulated to influence the retention of extinction.
Sangha, Susan; Ilenseer, Jasmin; Sosulina, Ludmila; Lesting, Jorg; Pape, Hans-Christian
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…
The expression of c-Fos and colocalisation of c-Fos and glucocorticoid receptors in brain structures of low and high anxiety rats subjected to extinction trials and re-learning of a conditioned fear response.
Lehner, Małgorzata; Wisłowska-Stanek, Aleksandra; Taracha, Ewa; Maciejak, Piotr; Szyndler, Janusz; Skórzewska, Anna; Turzyńska, Danuta; Sobolewska, Alicja; Hamed, Adam; Bidziński, Andrzej; Płaźnik, Adam
We designed an animal model to examine the mechanisms of differences in individual responses to aversive stimuli. We used the rat freezing response in the context fear test as a discriminating variable: low responders (LR) were defined as rats with a duration of freezing response one standard error or more below the mean value, and high responders (HR) were defined as rats with a duration of freezing response one standard error or more above the mean value. We sought to determine the colocalisation of c-Fos and glucocorticoid receptors-immunoreactivity (GR-ir) in HR and LR rats subjected to conditioned fear training, two extinction sessions and re-learning of a conditioned fear. We found that HR animals showed a marked decrease in conditioned fear in the course of two extinction sessions (16 days) in comparison with the control and LR groups. The LR group exhibited higher activity in the cortical M2 and prelimbic areas (c-Fos) and had an increased number of cells co-expressing c-Fos and GR-ir in the M2 and medial orbital cortex after re-learning a contextual fear. HR rats showed increased expression of c-Fos, GR-ir and c-Fos/GR-ir colocalised neurons in the basolateral amygdala and enhanced c-Fos and GR-ir in the dentate gyrus (DG) in comparison with LR animals. Our data indicate that recovery of a context-related behaviour upon re-learning of contextual fear is accompanied in HR animals by a selective increase in c-Fos expression and GRs-ir in the DG area of the hippocampus.
Villeneuve-Smith, Frank; Marshall, Liz; Munoz, Silvia
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.…
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…
Smith, Naftali R.; Meerson, Baruch
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.
Quiñones, María M.; Maldonado, Lizette; Velazquez, Bethzaly; Porter, James T.
Patients with post-traumatic stress disorder (PTSD) tend to show signs of a relatively increased inflammatory state suggesting that activation of the immune system may contribute to the development of PTSD. In the present study, we tested whether activation of the innate immune system can disrupt acquisition or recall of auditory fear extinction using an animal model of PTSD. Male adolescent rats received auditory fear conditioning in context A. The next day, an intraperitoneal injection of lipopolysaccharide (LPS; 100 μg/kg) prior to auditory fear extinction in context B impaired acquisition and recall of extinction. LPS (100 μg/kg) given after extinction training did not impair extinction recall suggesting that LPS did not affect consolidation of extinction. In contrast to cued fear extinction, contextual fear extinction was not affected by prior injection of LPS (100 μg/kg). Although LPS also reduced locomotion, we could dissociate the effects of LPS on extinction and locomotion by using a lower dose of LPS (50 μg/kg) which impaired locomotion without affecting extinction. In addition, 15 hrs after an injection of 250 μg/kg LPS in adult rats, extinction learning and recall were impaired without affecting locomotion. A sub-chronic treatment with candesartan, an angiotensin II type 1 receptor blocker, prevented the LPS-induced impairment of extinction in adult rats. Our results demonstrate that activation of the innate immune system can disrupt auditory fear extinction in adolescent and adult animals. These findings also provide direction for clinical studies of novel treatments that modulate the innate immune system for stress-related disorders like PTSD. PMID:26520214
Quiñones, María M; Maldonado, Lizette; Velazquez, Bethzaly; Porter, James T
Patients with post-traumatic stress disorder (PTSD) tend to show signs of a relatively increased inflammatory state suggesting that activation of the immune system may contribute to the development of PTSD. In the present study, we tested whether activation of the innate immune system can disrupt acquisition or recall of auditory fear extinction using an animal model of PTSD. Male adolescent rats received auditory fear conditioning in context A. The next day, an intraperitoneal injection of lipopolysaccharide (LPS; 100 μg/kg) prior to auditory fear extinction in context B impaired acquisition and recall of extinction. LPS (100 μg/kg) given after extinction training did not impair extinction recall suggesting that LPS did not affect consolidation of extinction. In contrast to cued fear extinction, contextual fear extinction was not affected by prior injection of LPS (100 μg/kg). Although LPS also reduced locomotion, we could dissociate the effects of LPS on extinction and locomotion by using a lower dose of LPS (50 μg/kg) which impaired locomotion without affecting extinction. In addition, 15 h after an injection of 250 μg/kg LPS in adult rats, extinction learning and recall were impaired without affecting locomotion. A sub-chronic treatment with candesartan, an angiotensin II type 1 receptor blocker, prevented the LPS-induced impairment of extinction in adult rats. Our results demonstrate that activation of the innate immune system can disrupt auditory fear extinction in adolescent and adult animals. These findings also provide direction for clinical studies of novel treatments that modulate the innate immune system for stress-related disorders like PTSD.
Thrailkill, Eric A; Bouton, Mark E
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
Raio, Candace M.; Brignoni-Perez, Edith; Goldman, Rachel; Phelps, Elizabeth A.
Extinction training is a form of inhibitory learning that allows an organism to associate a previously aversive cue with a new, safe outcome. Extinction does not erase a fear association, but instead creates a competing association that may or may not be retrieved when a cue is subsequently encountered. Characterizing the conditions under which extinction learning is expressed is important to enhancing the treatment of anxiety disorders that rely on extinction-based exposure therapy as a primary treatment technique. The ventromedial prefrontal cortex, which plays an important role in the expression of extinction memory, has been shown to be functionally impaired after stress exposure. Further, recent research in rodents found that exposure to stress led to deficits in extinction retrieval, although this has yet to be tested in humans. To explore how stress might influence extinction retrieval in humans, participants underwent a differential aversive learning paradigm, in which one image was probabilistically paired with an aversive shock while the other image denoted safety. Extinction training directly followed, at which point reinforcement was omitted. A day later, participants returned to the lab and either completed an acute stress manipulation (i.e., cold pressor), or a control task, before undergoing an extinction retrieval test. Skin conductance responses and salivary cortisol concentrations were measured throughout each session as indices of fear arousal and neuroendocrine stress responses, respectively. The efficacy of our stress induction was established by observing significant increases in cortisol for the stress condition only. We examined extinction retrieval by comparing conditioned responses during the last trial of extinction (day 1) with that of the first trial of re-extinction (day 2). Groups did not differ on initial fear acquisition or extinction, however, one day later participants in the stress group (n = 27) demonstrated significantly less
Leising, Kenneth J.; Wong, Jared; Blaisdell, Aaron P.
We investigated extinction and spontaneous recovery of spatial associations using a landmark-based appetitive search task in a touchscreen preparation with pigeons. Four visual landmarks (A, B, C, and D) were separately established as signals of a hidden reinforced target among an 8×7 array of potential target locations. The target was located above Landmarks A and C and below B and D. After conditioning, A and B were extinguished. Responding to A and C was assessed on probe tests 2 days following extinction, whereas, B and D were tested 14 days after extinction. We observed spontaneous recovery from spatial extinction following a 14-day, but not a 2-day, post-extinction retention interval. Furthermore, by plotting the spatial distribution of responding across the X and Y-axes during testing, we found that spontaneous recovery of responding to the target in our task was due to enhanced spatial control (i.e., a change in the overall distribution of responses) following the long delay to testing. These results add spatial extinction and spontaneous recovery to the list of findings supporting the assertion that extinction involves new learning that attenuates the originally acquired response, and that original learning of the spatial relationship between paired events survives extinction. PMID:26437383
Pace-Schott, Edward F; Germain, Anne; Milad, Mohammed R
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
Kwapis, Janine L; Jarome, Timothy J; Helmstetter, Fred J
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.
Radiske, Andressa; Rossato, Janine I; Köhler, Cristiano A; Gonzalez, Maria Carolina; Medina, Jorge H; Cammarota, Martín
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.
Raup, D. M.
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.
Zelikowsky, Moriel; Hast, Timothy A.; Bennett, Rebecca Z.; Merjanian, Michael; Nocera, Nathaniel A.; Ponnusamy, Ravikumar; Fanselow, Michael S.
Background Fears that are maladaptive or inappropriate can be reduced through extinction training. However, extinction is highly context-sensitive, resulting in the renewal of fear following shifts in context, and limiting the clinical efficacy of extinction training. Lesion and inactivation studies have shown that the contextualization of extinction depends on the hippocampus. Parallel studies have found that intrahippocampal scopolamine blocks contextual fear conditioning. Importantly, this effect was replicated using a non-invasive technique in which a low dose of scopolamine was administered systemically. We aimed to transfer the effects of this non-invasive approach to block the contextualization of fear extinction. Methods Rats were tone fear conditioned and extinguished under various systemic doses of scopolamine or the saline vehicle. They were subsequently tested (off drug) for tone fear in a context that was the same (controls) or shifted (renewal group) with respect to the extinction context. Results The lowest dose of scopolamine produced a significant attenuation of fear renewal when renewal was tested either in the original training context or a novel context. The drug also slowed the rate of long-term extinction memory formation, which was readily overcome by extending extinction training. Scopolamine only gave this effect when it was administered during, but not after extinction training. Higher doses of scopolamine severely disrupted extinction learning. Conclusions We discovered that disrupting contextual processing during extinction with the cholinergic antagonist scopolamine blocked subsequent fear renewal. Low doses of scopolamine may be a clinically promising adjunct to exposure therapy by making extinction more relapse-resistant. PMID:22981655
Barad, Mark; Gean, Po-Wu; Lutz, Beat
The amygdala has long been known to play a central role in the acquisition and expression of fear. More recently, convergent evidence has implicated the amygdala in the extinction of fear as well. In rodents, some of this evidence comes from the infusion of drugs directly into the amygdala and, in particular, into the basolateral complex of the amygdala, during or after extinction learning. In vivo electrophysiology has identified cellular correlates of extinction learning and memory in the lateral nucleus of that structure. Human imaging experiments also indicate that amygdaloid activity correlates with extinction training. In addition, some studies have directly identified changes in molecular constituents of the basolateral amygdala. Together these experiments strongly indicate that the basolateral amygdala plays a crucial role in extinction learning. Interpreted in the light of these findings, several recent in vitro electrophysiology studies in amygdala-containing brain slices are suggestive of potential synaptic and circuit bases of extinction learning.
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.
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.
Giblin, Jay; Vietmeyer, Felix; McDonald, Matthew P; Kuno, Masaru
Here we show the first direct extinction spectra of single one-dimensional (1D) semiconductor nanostructures obtained at room temperature utilizing a spatial modulation approach. (1) For these materials, ensemble averaging in conventional extinction spectroscopy has limited our understanding of the interplay between carrier confinement and their electrostatic interactions. (2-4) By probing individual CdSe nanowires (NWs), we have identified and assigned size-dependent exciton transitions occurring across the visible. In turn, we have revealed the existence of room temperature 1D excitons in the narrowest NWs.
Raup, D. M.
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.
Harloe, John P.; Thorpe, Andrew J.; Lichtman, Aron H.
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…
Laurent, Vincent; Westbrook, R. Frederick
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…
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.
Almeida-Corrêa, Suellen; Moulin, Thiago C; Carneiro, Clarissa F D; Gonçalves, Marina M C; Junqueira, Lara S; Amaral, Olavo B
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.
Hylander, Kristoffer; Ehrlén, Johan
Extinction debts can result from many types of habitat changes involving mechanisms other than metapopulation processes. This is a fact that most recent literature on extinction debts pays little attention to. We argue that extinction debts can arise because (i) individuals survive in resistant life-cycle stages long after habitat quality change, (ii) stochastic extinctions of populations that have become small are not immediate, and (iii) metapopulations survive long after that connectivity has decreased if colonization-extinction dynamics is slow. A failure to distinguish between these different mechanisms and to simultaneously consider both the size of the extinction debt and the relaxation time hampers our understanding of how extinction debts arise and our ability to prevent ultimate extinctions.
Leising, Kenneth J; Wong, Jared; Blaisdell, Aaron P
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
Furlong, Teri M; Richardson, Rick; McNally, Gavan P
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.
Allmon, Warren Douglas
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)
McNally, Gavan P
Extinction training can reduce drug seeking behavior. This article reviews the neural circuits that contribute to extinction and approaches to enhancing the efficacy of extinction. Extinction of drug seeking depends on cortical-striatal-hypothalamic and cortical-hypothalamic-thalamic pathways. These pathways interface, in the hypothalamus and thalamus respectively, with the neural circuits controlling reinstatement of drug seeking. The actions of these pathways at lateral hypothalamic orexin neurons, and of perifornical/dorsomedial hypothalamic derived opioid peptides at kappa opioid receptors in the paraventricular thalamus, are important for inhibiting drug seeking. Despite effectively reducing or inhibiting drug seeking in the short term, extinguished drug seeking is prone to relapse. Three different strategies to augment extinction learning or retrieval are reviewed: pharmacological augmentation, retrieval - extinction training, and provision of extinction memory retrieval cues. These strategies have been used in animal models and with human drug users to enhance extinction or cue exposure treatments. They hold promise as novel strategies to promote abstinence from drug seeking. This article is part of a Special Issue entitled 'NIDA 40th Anniversary Issue'.
Malvaez, Melissa; McQuown, Susan C; Rogge, George A; Astarabadi, Mariam; Jacques, Vincent; Carreiro, Samantha; Rusche, James R; Wood, Marcelo A
Nonspecific histone deacetylase (HDAC) inhibition has been shown to facilitate the extinction of drug-seeking behavior in a manner resistant to reinstatement. A key open question is which specific HDAC is involved in the extinction of drug-seeking behavior. Using the selective HDAC3 inhibitor RGFP966, we investigated the role of HDAC3 in extinction and found that systemic treatment with RGFP966 facilitates extinction in mice in a manner resistant to reinstatement. We also investigated whether the facilitated extinction is related to the enhancement of extinction consolidation during extinction learning or to negative effects on performance or reconsolidation. These are key distinctions with regard to any compound being used to modulate extinction, because a more rapid decrease in a defined behavior is interpreted as facilitated extinction. Using an innovative combination of behavioral paradigms, we found that a single treatment of RGFP966 enhances extinction of a previously established cocaine-conditioned place preference, while simultaneously enhancing long-term object-location memory within subjects. During extinction consolidation, HDAC3 inhibition promotes a distinct pattern of histone acetylation linked to gene expression within the infralimbic cortex, hippocampus, and nucleus accumbens. Thus, the facilitated extinction of drug-seeking cannot be explained by adverse effects on performance. These results demonstrate that HDAC3 inhibition enhances the memory processes involved in extinction of drug-seeking behavior.
Bredy, Timothy W.; Wu, Hao; Crego, Cortney; Zellhoefer, Jessica; Sun, Yi E.; Barad, Mark
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,…
Davis, Adeola R.; Shields, Angela D.; Brigman, Jonathan L.; Norcross, Maxine; McElligott, Zoe A.; Holmes, Andrew; Winder, Danny G.
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…
Hartley, N D; Gunduz-Cinar, O; Halladay, L; Bukalo, O; Holmes, A; Patel, S
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.
Hartley, N D; Gunduz-Cinar, O; Halladay, L; Bukalo, O; Holmes, A; Patel, S
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
Hartley, Catherine A; Gorun, Alyson; Reddan, Marianne C; Ramirez, Franchesca; Phelps, Elizabeth A
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.
Alvarez, Ruben P.; Johnson, Linda; Grillon, Christian
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…
Sturrock, P. A.; Baker, K.; Turk, J. S.
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.
Giovanelli, Riccardo; Haynes, Martha P.; Salzer, John J.; Wegner, Gary; da Costa, Luiz N.; Freudling, Wolfram
We analyze the photometric properties of a sample of Sbc-Sc galaxies with known redshifts, single-dish H I profiles, and Charge Coupled Device (CCD) I band images. We derive laws that relate the measured isophotal radius at muI = 23.5, magnitude, scale length, and H I flux to the face-on aspect. We find spiral galaxies to be substantially less transparent than suggested in most previous determinations, but not as opaque as claimed by Valentijn (1990). Regions in the disk farther than two or three scale lengths from the center are close to completely transparent. In addition to statistically derived relations for the inclination dependence of photometric parameters, we present the results of a modeling exercise that utilizes the 'triplex' model of Disney et al. (1989) to obtain upper limits of the disk opacity. Within the framework of that model, and with qualitative consideration of the effects of scattering on extinction, we estimate late spiral disks at I band to have central optical depths tauI(0) less than 5 and dust absorbing layers with scale heights on the order of half that of the stellar component or less. We discuss our results in light of previous determinations of internal extinction relations and point out the substantial impact of internal extinction on the scatter of the Tully-Fisher relation. We also find that the visual diameters by which large catalogs are constructed (UGC, ESO-Uppsala) are nearly proportional to face-on isophotal diameters.
Revillo, D A; Paglini, M G; Arias, C
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
Waltereit, Robert; Mannhardt, Sönke; Nescholta, Sabine; Maser-Gluth, Christiane; Bartsch, Dusan
Memory extinction, defined as a decrease of a conditioned response as a function of a non-reinforced conditioned stimulus presentation, has high biological and clinical relevance. Extinction is not a passive reversing or erasing of the plasticity associated with acquisition, but a novel, active learning process. Nifedipine blocks L-type voltage gated calcium channels (LVGCC) and has been shown previously to selectively interfere with the extinction, but not the acquisition, of fear memory. We studied here the effect of retrograde and anterograde shifts of nifedipine application, with respect to an extinction training, on the extinction of fear conditioning. Subcutaneous injection of 30 mg/kg nifedipine, at least up to 4 h before the extinction session, significantly impaired extinction, as did intraperitoneal injection of 15 mg/kg nifedipine, at least up to 2 h before extinction training. However, the injection of nifedipine also induced a strong and protracted stress response. The pharmacokinetics of nifedipine suggest that it was mainly this stress response that triggered the specific inhibition of extinction, not the blockade of LVGCC in the brain. Our results support recent findings that stress selectively interferes with the extinction, but not the acquisition, of fear memory. They also indicate that a pharmacological approach is not sufficient to study the role of brain LVGCC in learning and memory. Further research using specific genetically modified animals is necessary to delineate the role of LVGCC in fear memory extinction.
Raczka, K A; Mechias, M-L; Gartmann, N; Reif, A; Deckert, J; Pessiglione, M; Kalisch, R
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.
Burghardt, Nesha S.; Sigurdsson, Torfi; Gorman, Jack M.; McEwen, Bruce S.; LeDoux, Joseph E.
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
Goodman, Jarid; Packard, Mark G.
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
Abstract This is Chapter Thirteen of Leaving Liza, a novel about life, death, love, friendship, jealousy and lesbian ex-lovers. In the novel, six women are spending the weekend at a beach house in Long Island's Hamptons, where they have gathered to be with their friend Liza, who is battling terminal ovarian cancer. Liza's lover, Jill, has agreed to the house party and helped plan the guest list. But, as she smolders with resentment at the attention Liza is getting and the depth of the women's friendships, she begins to come unraveled. After a severe asthma attack that requires an emergency room visit the day before, Jill conducts a seance, purporting to have contacted another of Liza's ex-lovers, who died a few months earlier. Now, on this last night of the house party, she lets Liza and her friends know what she's really feeling. The editors have asked me to add some "commentary" on the questions this story raises about the roles of ex-lovers. I would hope the scene reflects some of the tensions that can occur when ex-lovers choose to remain friends, particularly when those bonds provoke profound jealousy in both current and ex-lovers. For many of us, the job of assuaging and reassuring the current lover while maintaining intimate friendships with an ex-lover is simply too exhausting and prickly to endure. For others, it is worth the struggle. Liza and her friends clearly think it is. But at what point, they all wonder at this house party, does their hunger for honesty and their anger at being insulted and manipulated become more important than keeping the peace, and possibly their friendship with Liza? Perhaps only Liza's death will free them from this compromising coexistence.
Niemi, Maj-Britt; Härting, Margarete; Kou, Wei; Del Rey, Adriana; Besedovsky, Hugo O; Schedlowski, Manfred; Pacheco-López, Gustavo
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.
Bahari-Javan, Sanaz; Maddalena, Andrea; Kerimoglu, Cemil; Wittnam, Jessica; Held, Torsten; Bähr, Mathias; Burkhardt, Susanne; Delalle, Ivanna; Kügler, Sebastian; Fischer, Andre; Sananbenesi, Farahnaz
Histone acetylation has been implicated with the pathogenesis of neuropsychiatric disorders and targeting histone deacetylases (HDACs) using HDAC inhibitors was shown to be neuroprotective and to initiate neuroregenerative processes. However, little is known about the role of individual HDAC proteins during the pathogenesis of brain diseases. HDAC1 was found to be upregulated in patients suffering from neuropsychiatric diseases. Here, we show that virus-mediated overexpression of neuronal HDAC1 in the adult mouse hippocampus specifically affects the extinction of contextual fear memories, while other cognitive abilities were unaffected. In subsequent experiments we show that under physiological conditions, hippocampal HDAC1 is required for extinction learning via a mechanism that involves H3K9 deacetylation and subsequent trimethylation of target genes. In conclusion, our data show that hippocampal HDAC1 has a specific role in memory function.
Vroling, Maartje S; de Jong, Peter J
Some people show slower extinction of UCS expectancies than other people. Little is known about what predicts such delayed extinction. Extinction requires that people deduce the logical implication of corrective experiences challenging the previously learned CS-UCS contingency. "A strong habitual tendency to confirm beliefs" may therefore be a powerful mechanism immunising against refutation of UCS expectancies. This study investigated whether individual differences in such a belief confirming tendency (a process called "belief bias") may help in explaining individual differences in extinction. We tested whether relatively strong belief bias predicts delayed extinction of experimentally induced UCS expectancies. In a differential aversive conditioning paradigm, we used UCS-irrelevant (Experiment 1) and UCS-relevant (Experiment 2) pictorial stimuli as CS⁺ and CS⁻, and electrical stimulation as UCS. Belief bias indeed predicted delayed extinction of UCS expectancies when the CS⁺ was UCS-relevant (as is typically the case for phobic stimuli, Experiment 2). The study provides preliminary evidence that enhanced belief bias may indeed play a role in the persistence of UCS expectancies, and can thereby contribute to the development and persistence of anxiety disorders. The results also point to the relevance of reasoning tendencies in the search for predictors of delayed extinction of UCS expectancies.
Marks, Elizabeth H; Zoellner, Lori A
Exposure-based therapies for posttraumatic stress disorder are thought to reduce intrusive memories through extinction processes. Methods that enhance extinction may translate to improved treatment. Rat research suggests retrieving a memory via a conditioned stimulus (CS) cue, and then modifying the retrieved memory within a specific reconsolidation window may enhance extinction. In humans, studies (e.g., Kindt & Soeter, 2013; Schiller et al., 2010) using basic learning paradigms show discrepant findings. Using a distressing film paradigm, participants (N = 148) completed fear acquisition and extinction. At extinction, they were randomized to 1 of 3 groups: CS cue within reconsolidation window, CS cue outside window, or non-CS cue within window. Intrusions were assessed 24 hr after extinction. Participants receiving the CS cue and completing extinction within the reconsolidation window had more intrusions (M = 2.40, SD = 2.54) than those cued outside (M = 1.65, SD = 1.70) or those receiving a non-CS cue (M = 1.24, SD = 1.26), F(2, 145) = 4.52, p = .01, d = 0.55. Consistent with the reconsolidation hypothesis, presenting a CS cue does appear to activate a specific period of time during which a memory can be updated. However, the CS cue caused increased, rather than decreased, frequency of intrusions. Understanding parameters of preextinction cueing may help us better understand reconsolidation as a potential memory updating mechanism.
Asteroid 2011 AG5 will impact on Earth in 2040. (See Donald K. Yoemans, ``Asteroid 2011 AG5 - A Reality Check,'' NASA-JPL, 2012) In 2011, The author say: the dark hole will take the dark comet to impact our solar system in 20 years, and give a systemic model between the sun and its companion-dark hole to explain why were there periodicity mass extinction on earth. (see Dayong Cao, BAPS.2011.CAL.C1.7, BAPS.2011.DFD.LA.24, BAPS.2012.APR.K1.78 and BAPS.2011.APR.K1.17) The dark Asteroid 2011 AG5 (as a dark comet) is made of the dark matter which has a space-time (as frequence-amplitude square) center- a different systemic model from solar systemic model. It can asborb the space-time and wave. So it is ``dark.'' When many dark matters hit on our earth, they can break our atom structure and our genetic code to trigger the Mass Extinction. In our experiments, consciousness can change the systematic model and code by a life-informational technology. So it can change the output signals of the solar cell. (see Dayong Cao, BAPS.2011.MAR.C1.286 and BAPS.2012.MAR.P33.14) So we will develop the genetic code of lives to evolution and sublimation, will use the dark matter to change the systemic model between dark hole and sun and will avoid next extinction.
safety learning , and sleep in humans. The Journal of Neuroscience , 34(35), 11754-11760. Fear conditioning is considered an animal model of...recall of extinction learning , and that the REM sleep stage is associated with ability to recall extinction as well as recall safety signal learning ...Drummond also conducted a number of media interviews related to the Journal of Neuroscience paper described below. In 2015 Ms. Straus has made national
Adatte, Thierry; Sordet, Valentin; Keller, Gerta; Schoene, Blair; Samperton, Kyle; Khadri, Syed
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
Sepkoski, J. John, Jr.; Raup, David M.
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.
Flessa, Karl W.
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.
Abend, R; Jalon, I; Gurevitch, G; Sar-el, R; Shechner, T; Pine, D S; Hendler, T; Bar-Haim, Y
Research associates processes of fear conditioning and extinction with treatment of anxiety and stress-related disorders. Manipulation of these processes may therefore be beneficial for such treatment. The current study examines the effects of electrical brain stimulation on fear extinction processes in healthy humans in order to assess its potential relevance for treatment enhancement. Forty-five participants underwent a 3-day fear conditioning and extinction paradigm. Electrical stimulation targeting the medial prefrontal cortex was applied during the extinction-learning phase (Day 2). Participants were randomly assigned to three stimulation conditions: direct-current (DC) stimulation, aimed at enhancing extinction-learning; low-frequency alternating-current (AC) stimulation, aimed at interfering with reconsolidation of the activated fear memory; and sham stimulation. The effect of stimulation on these processes was assessed in the subsequent extinction recall phase (Day 3), using skin conductance response and self-reports. Results indicate that AC stimulation potentiated the expression of fear response, whereas DC stimulation led to overgeneralization of fear response to non-reinforced stimuli. The current study demonstrates the capability of electrical stimulation targeting the medial prefrontal cortex to modulate fear extinction processes. However, the stimulation parameters tested here yielded effects opposite to those anticipated and could be clinically detrimental. These results highlight the potential capacity of stimulation to manipulate processes relevant for treatment of anxiety and stress-related disorders, but also emphasize the need for additional research to identify delivery parameters to enable its translation into clinical practice. Clinical trial identifiers: Modulation of Fear Extinction Processes Using Transcranial Electrical Stimulation; https://clinicaltrials.gov/show/NCT02723188; NCT02723188 NCT02723188. PMID:27727241
Schiller, Daniela; Kanen, Jonathan W.; LeDoux, Joseph E.; Monfils, Marie-H.; Phelps, Elizabeth A.
Controlling learned defensive responses through extinction does not alter the threat memory itself, but rather regulates its expression via inhibitory influence of the prefrontal cortex (PFC) over amygdala. Individual differences in amygdala–PFC circuitry function have been linked to trait anxiety and posttraumatic stress disorder. This finding suggests that exposure-based techniques may actually be least effective in those who suffer from anxiety disorders. A theoretical advantage of techniques influencing reconsolidation of threat memories is that the threat representation is altered, potentially diminishing reliance on this PFC circuitry, resulting in a more persistent reduction of defensive reactions. We hypothesized that timing extinction to coincide with threat memory reconsolidation would prevent the return of defensive reactions and diminish PFC involvement. Two conditioned stimuli (CS) were paired with shock and the third was not. A day later, one stimulus (reminded CS+) but not the other (nonreminded CS+) was presented 10 min before extinction to reactivate the threat memory, followed by extinction training for all CSs. The recovery of the threat memory was tested 24 h later. Extinction of the nonreminded CS+ (i.e., standard extinction) engaged the PFC, as previously shown, but extinction of the reminded CS+ (i.e., extinction during reconsolidation) did not. Moreover, only the nonreminded CS+ memory recovered on day 3. These results suggest that extinction during reconsolidation prevents the return of defensive reactions and diminishes PFC involvement. Reducing the necessity of the PFC–amygdala circuitry to control defensive reactions may help overcome a primary obstacle in the long-term efficacy of current treatments for anxiety disorders. PMID:24277809
Gallistel, C. R.
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
Gallistel, C R
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.
Furlong, T M; Pan, M J; Corbit, L H
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
Rosa, Jessica; Myskiw, Jociane C; Furini, Cristiane R G; Sapiras, Gerson G; Izquierdo, Ivan
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.
Furlong, T M; Pan, M J; Corbit, L H
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.
... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Leave from former leave systems. 630.503... AND LEAVE Recredit of Leave § 630.503 Leave from former leave systems. An employee who earned leave under the leave acts of 1936 or any other leave system merged under subchapter I of chapter 63 of...
Dunsmoor, Joseph E; Ahs, Fredrik; Zielinski, David J; LaBar, Kevin S
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.
Melchers, Klaus G; Wolff, Susann; Lachnit, Harald
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.
Briggs, James F.; Olson, Brian P.
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…
Melo, Irene; Ehrlich, Ingrid
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.
Davis, Michael; Myers, Karyn M.; Ressler, Kerry J.
Fear extinction is defined as a decline in conditioned fear responses (CRs) following nonreinforced exposure to a feared conditioned stimulus (CS). Behavioral evidence indicates that extinction is a form of inhibitory learning: Extinguished fear responses reappear with the passage of time (spontaneous recovery), a shift of context (renewal), and…
Schiller, Daniela; Cain, Christopher K.; Curley, Nina G.; Schwartz, Jennifer S.; Stern, Sarah A.; LeDoux, Joseph E.; Phelps, Elizabeth A.
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…
Brown, Kevin L.; Freeman, John H.
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…
Kwapis, Janine L.; Jarome, Timothy J.; Helmstetter, Fred J.
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…
Waltereit, Robert; Mannhardt, Sonke; Nescholta, Sabine; Maser-Gluth, Christiane; Bartsch, Dusan
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…
Rabinak, Christine A; Phan, K Luan
Anxiety disorders, such as post-traumatic stress (PTSD), panic, and phobic disorders, can be conceptualized as a failure to inhibit inappropriate fear responses. A common, effective treatment strategy involves repeated presentations to the feared cue without any danger (extinction). However, extinction learning has a number of important limitations, and enhancing its effects, generalizability and durability via cognitive enhancers may improve its therapeutic impact. In this review we focus specifically on the role of the cannabinoid system in fear extinction learning and its retention. We address the following questions: What are the neural circuits mediating fear extinction?; Can we make fear extinction more effective?; Can cannabinoids facilitate fear extinction in humans?; How might the cannabinoid system effect fear extinction? Collectively, translational evidence suggest that enhancing cannabinoid transmission may facilitate extinction learning and its recall, and that the cannabinoid system is a potential pharmacological target for improving the active learning that occurs during exposure-based behavioral treatments prompting future research in terms of mechanisms research, novel treatment approaches ('cognitive enhancers'), and pharmacotherapeutic drug discovery.
Ray, Tane; Moseley, Leo; Jan, Naeem
We analyse the fossil data of Benton1 with and without interpolation schemes. By Fourier transform analysis, we find a frequency dependence of the amplitude of 1/f for the various interpolation schemes used in the past. We illustrate that shuffling the interpolated data changes the spectra only slightly. On the other hand, an identical analysis performed on the raw (uninterpolated) fossil data gives a flat frequency spectrum. We conclude that the 1/f behavior is an artifact of the interpolation schemes. We next introduce a simulation of extinctions driven only by interactions between two trophic levels. Fourier transform analysis of the simulation data shows a frequency dependence of 1/f. When the data are grouped into a form resembling the fossil record the frequency dependence vanishes, giving a flat spectrum. Our simulation produces a frequency spectrum that agrees with the observed fossil record.
Norris, Andrew N.
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
Ricketts, Taylor H; Dinerstein, Eric; Boucher, Tim; Brooks, Thomas M; Butchart, Stuart H M; Hoffmann, Michael; Lamoreux, John F; Morrison, John; Parr, Mike; Pilgrim, John D; Rodrigues, Ana S L; Sechrest, Wes; Wallace, George E; Berlin, Ken; Bielby, Jon; Burgess, Neil D; Church, Don R; Cox, Neil; Knox, David; Loucks, Colby; Luck, Gary W; Master, Lawrence L; Moore, Robin; Naidoo, Robin; Ridgely, Robert; Schatz, George E; Shire, Gavin; Strand, Holly; Wettengel, Wes; Wikramanayake, Eric
Slowing rates of global biodiversity loss requires preventing species extinctions. Here we pinpoint centers of imminent extinction, where highly threatened species are confined to single sites. Within five globally assessed taxa (i.e., mammals, birds, selected reptiles, amphibians, and conifers), we find 794 such species, three times the number recorded as having gone extinct since 1500. These species occur in 595 sites, concentrated in tropical forests, on islands, and in mountainous areas. Their taxonomic and geographical distribution differs significantly from that of historical extinctions, indicating an expansion of the current extinction episode beyond sensitive species and places toward the planet's most biodiverse mainland regions. Only one-third of the sites are legally protected, and most are surrounded by intense human development. These sites represent clear opportunities for urgent conservation action to prevent species loss.
Mead, Jim I.; Martin, Paul S.; Euler, Robert C.; Long, Austin; Jull, A. J. T.; Toolin, Laurence J.; Donahue, Douglas J.; Linick, T. W.
Keratinous horn sheaths of the extinct Harrington's mountain goat, Oreamnos harringtoni, were recovered at or near the surface of dry caves of the Grand Canyon, Arizona. Twenty-three separate specimens from two caves were dated nondestructively by the tandem accelerator mass spectrometer (TAMS). Both the TAMS and the conventional dates indicate that Harrington's mountain goat occupied the Grand Canyon for at least 19,000 years prior to becoming extinct by 11,160 ± 125 radiocarbon years before present. The youngest average radiocarbon dates on Shasta ground sloths, Nothrotheriops shastensis, from the region are not significantly younger than those on extinct mountain goats. Rather than sequential extinction with Harrington's mountain goat disappearing from the Grand Canyon before the ground sloths, as one might predict in view of evidence of climatic warming at the time, the losses were concurrent. Both extinctions coincide with the regional arrival of Clovis hunters. Images PMID:16593655
Bless, R. C.; Savage, B. D.
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.
Mead, Jim I.; Martin, Paul S.; Euler, Robert C.; Long, Austin; Jull, A. J. T.; Toolin, Laurence J.; Donahue, Douglas J.; Linick, T. W.
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.
Mead, J.I.; Martin, P.S.; Euler, R.C.; Long, A.; Jull, A.J.T.; Toolin, L.J.; Donahue, D.J.; Linick, T.W.
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.
Zimmer, Peter C.; McGraw, J. T.; Gimmestad, G. G.; Roberts, D.; Stewart, J.; Smith, J.; Fitch, J.
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.
Baker, Kathryn D; McNally, Gavan P; Richardson, Rick
The NMDA receptor partial agonist d-cycloserine (DCS) enhances the extinction of learned fear in rats and exposure therapy in humans with anxiety disorders. Despite these benefits, little is known about the mechanisms by which DCS promotes the loss of fear. The present study examined whether DCS augments extinction retention (1) through reductions in conditioned stimulus (CS) processing or (2) by promoting the development of conditioned inhibition to contextual cues. Rats administered DCS prior to extinction showed enhanced long-term extinction retention (Experiments 3 and 4). The same nonreinforced CS procedure used in extinction also reduced freezing at test when presented as pre-exposure before conditioning, demonstrating latent inhibition (Experiment 1). DCS administered shortly prior to pre-exposure had no effect on latent inhibition using parameters which produced weak (Experiment 2) or strong (Experiment 3) expression of latent inhibition. Therefore, DCS facilitated learning involving CS-alone exposures, but only when these exposures occurred after (extinction) and not before (latent inhibition) conditioning. We also used a retardation test procedure to examine whether the extinction context gained inhibitory properties for rats given DCS prior to extinction. With three different footshock intensities, there was no evidence that DCS promoted accrual of associative inhibition to the extinction context (Experiment 4). The present findings demonstrate that DCS does not facilitate extinction by reducing CS processing or causing the extinction context to become a conditioned inhibitor. Investigations into the mechanisms underlying the augmentation of extinction by DCS are valuable for understanding how fear can be inhibited.
Erwin, D. H.
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.
Gu, Li; Xue, Lichun; Song, Qi; Wang, Fengji; He, Huaqin; Zhang, Zhongyi
During commercial transactions, the quality of flue-cured tobacco leaves must be characterized efficiently, and the evaluation system should be easily transferable across different traders. However, there are over 3000 chemical compounds in flue-cured tobacco leaves; thus, it is impossible to evaluate the quality of flue-cured tobacco leaves using all the chemical compounds. In this paper, we used Support Vector Machine (SVM) algorithm together with 22 chemical compounds selected by ReliefF-Particle Swarm Optimization (R-PSO) to classify the fragrant style of flue-cured tobacco leaves, where the Accuracy (ACC) and Matthews Correlation Coefficient (MCC) were 90.95% and 0.80, respectively. SVM algorithm combined with 19 chemical compounds selected by R-PSO achieved the best assessment performance of the aromatic quality of tobacco leaves, where the PCC and MSE were 0.594 and 0.263, respectively. Finally, we constructed two online tools to classify the fragrant style and evaluate the aromatic quality of flue-cured tobacco leaf samples. These tools can be accessed at http://bioinformatics.fafu.edu.cn/tobacco .
Weir, Catherine; Toland, Cynthia; King, Rose Ann; Martin, Lisa Maas
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…
Peters, Jamie; Kalivas, Peter W.; Quirk, Gregory J.
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…
McHugh, Louise; Procter, Jonathan; Herzog, Michaela; Schock, Anne-Kathrin; Reed, Phil
In the present experiments, we investigated the effects of mindfulness on behavioral extinction and resurgence. Participants received instrumental training; either they received FI training (Experiment 1), or they were trained to emit high rates and low rates of response via exposure to a multiple VR yoked-VI schedule prior to exposure to a multiple FI FI schedule in order to alter their rates of responding learned during Experiment 2. Participants were then exposed to either a focused- (mindfulness) or an unfocused-attention induction task. All participants were finally exposed to an extinction schedule in order to determine whether a mindfulness induction task presented immediately prior to extinction training affected extinction (Experiment 1) and behavioral resurgence (Experiment 2). During the extinction phase, the rates of responding were higher in the control group than in the mindfulness group, indicating that the mindfulness group was more sensitive to the contingencies and, thus, their prior performance extinguished more readily (Experiment 1). Moreover, rates of response in the extinction components less precisely reflected previous training in the mindfulness group, suggesting less resurgence of past behaviors after the mindfulness induction (Experiment 2).
Morris, M D; Gebhart, G F
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.
Miller, Ralph R; Laborda, Mario A; Polack, Cody W; Miguez, Gonzalo
Exposure to a cue alone either before (i.e., latent inhibition treatment) or after (i.e., extinction) the cue is paired with an unconditioned stimulus results in attenuated conditioned responding to the cue. Here we report two experiments in which potential parallels between the context specificity of the effects of extinction and latent inhibition treatments were directly compared in a lick suppression preparation with rats. The reversed ordering of conditioning and nonreinforcement in extinction and latent inhibition designs allowed us to examine the effect of training order on the context specificity of what is learned given phasic reinforcement and nonreinforcement of a target cue. Experiment 1 revealed that when conditioned-stimulus (CS) conditioning and CS nonreinforcement were administered in the same context, both extinction and latent inhibition treatments had reduced impacts on test performance, relative to excitatory conditioning when testing occurred outside the treatment context. Similarly, Experiment 2 showed that when conditioning was administered in one context and nonreinforcement was administered in a second context, the effects of both extinction and latent inhibition treatments were attenuated when testing occurred in a neutral context, relative to the context in which the CS was nonreinforced. The observed context specificity of extinction and latent inhibition treatments has been previously reported in both cases, but not in a single experiment under otherwise identical conditions. The results of the two experiments convergently suggest that memory of nonreinforcement becomes context dependent after a cue is both reinforced and nonreinforced, independent of the order of training.
Miller, Ralph R.; Laborda, Mario A.; Polack, Cody W.; Miguez, Gonzalo
Exposure to a cue alone either before (i.e., latent inhibition treatment) or after (i.e., extinction) the cue is paired with an unconditioned stimulus (US) results in attenuated conditioned responding to the cue. Here we report two experiments in which potential parallels between the context specificity of the effects of extinction and latent inhibition treatments were directly compared in a lick suppression preparation with rats. The reversed ordering of conditioning and nonreinforcement in extinction and latent inhibition designs allowed us to examine the effect of training order on the context specificity of what is learned given phasic reinforcement and nonreinforcement of a target cue. Experiment 1 found that when CS conditioning and CS nonreinforcement were administered in the same context, both extinction and latent inhibition treatments had reduced impact on test performance relative to excitatory conditioning when testing occurred outside the treatment context. Similarly, Experiment 2 found that when conditioning was administered in one context and nonreinforcement was administered in a second context, the effects of both extinction and latent inhibition treatments were attenuated when testing occurred in a neutral context relative to the context in which the CS was nonreinforced. The observed context specificity of extinction and latent inhibition treatments have both been previously reported, but not in a single experiment under otherwise identical conditions. The results of the two experiments convergently suggest that memory of nonreinforcement becomes context dependent after a cue is both reinforced and nonreinforced independent of the order of training. PMID:26100525
Delamater, Andrew R
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.
Delamater, Andrew R.
This paper reviews a variety of studies designed to examine the effects of extinction upon control by specific stimulus-outcome (S-O) associations in Pavlovian conditioning. Studies conducted with rats in a magazine approach conditioning paradigm have shown that control by specific S-O associations is normally unaffected by extinction treatments, although other aspects of conditioned responding seem affected in a more enduring way. However, recent work suggests that extinction can undermine control by such associations if it is administered after the conditioned stimulus is weakly encoded. The results from these studies suggest that it may be important to consider multiple response systems in assessing the impact of extinction. Studies conducted with the flavor preference learning paradigm in rats also show that specific S-O associations can be undermined by procedures that involve presenting a flavor cue in the absence of its associated nutrient. These findings provide no support for the view that flavor preference learning necessarily entails some unique learning process that differs from more conventional processes. As in other situations, some of these effects likely involve a masking process, but the extent to which masking or true associative weakening occurs in extinction more generally is a topic that is not well understood. Finally, we present some data to suggest that extinction also involves conditional “occasion-setting” control by contextual cues. Special procedures are recommended in assessing such learning when the goal is to distinguish this form of learning from other more conventional mechanisms of extinction. PMID:22465262
Méndez-Couz, M; Conejo, N M; Vallejo, G; Arias, J L
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.
Verma, Dilip; Wood, James; Lach, Gilliard; Herzog, Herbert; Sperk, Guenther; Tasan, Ramon
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.
Verma, Dilip; Wood, James; Lach, Gilliard; Herzog, Herbert; Sperk, Guenther; Tasan, Ramon
Emotions control evolutionarily-conserved behavior that is central to survival in a natural environment. Imbalance within emotional circuitries, however, may result in malfunction and manifestation of anxiety disorders. Thus, a better understanding of emotional processes and, in particular, the interaction of the networks involved is of considerable clinical relevance. Although neurobiological substrates of emotionally controlled circuitries are increasingly evident, their mutual influences are not. To investigate interactions between hunger and fear, we performed Pavlovian fear conditioning in fasted wild-type mice and in mice with genetic modification of a feeding-related gene. Furthermore, we analyzed in these mice the electrophysiological microcircuits underlying fear extinction. Short-term fasting before fear acquisition specifically impaired long-term fear memory, whereas fasting before fear extinction facilitated extinction learning. Furthermore, genetic deletion of the Y4 receptor reduced appetite and completely impaired fear extinction, a phenomenon that was rescued by fasting. A marked increase in feed-forward inhibition between the basolateral and central amygdala has been proposed as a synaptic correlate of fear extinction and involves activation of the medial intercalated cells. This form of plasticity was lost in Y4KO mice. Fasting before extinction learning, however, resulted in specific activation of the medial intercalated neurons and re-established the enhancement of feed-forward inhibition in this amygdala microcircuit of Y4KO mice. Hence, consolidation of fear and extinction memories is differentially regulated by hunger, suggesting that fasting and modification of feeding-related genes could augment the effectiveness of exposure therapy and provide novel drug targets for treatment of anxiety disorders. PMID:26062787
Gilbert, Benjamin; Levine, Jonathan M
Whether introduced species invasions pose a major threat to biodiversity is hotly debated. Much of this debate is fueled by recent findings that competition from introduced organisms has driven remarkably few plant species to extinction. Instead, native plant species in invaded ecosystems are often found in refugia: patchy, marginal habitats unsuitable to their nonnative competitors. However, whether the colonization and extinction dynamics of these refugia allow long-term native persistence is uncertain. Of particular concern is the possibility that invasive plants may induce an extinction debt in the native flora, where persistence over the short term masks deterministic extinction trajectories. We examined how invader impacts on landscape structure influence native plant persistence by combining recently developed quantitative techniques for evaluating metapopulation persistence with field measurements of an invaded plant community. We found that European grass invasion of an edaphically heterogeneous California landscape has greatly decreased the likelihood of the persistence of native metapopulations. It does so via two main pathways: (i) decreasing the size of native refugia, which reduces seed production and increases local extinction, and (ii) eroding the dispersal permeability of the matrix between refugia, which reduces their connectivity. Even when native plant extinction is the deterministic outcome of invasion, the time to extinction can be on the order of hundreds of years. We conclude that the relatively short time since invasion in many parts of the world is insufficient to observe the full impact of plant invasions on native biodiversity.
Ward, P. D.
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.
De Marchi, Guido; Panagia, Nino
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.
Panayi, Marios C; Killcross, Simon
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.
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.
Cheung, Timothy H C; Neisewander, Janet L; Sanabria, Federico
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.
MacKillop, James; Lisman, Stephen A
Cue exposure treatment (CET) attempts to reduce the influence of conditioned substance cues on addictive behavior via extinction, but has received only modest empirical support in clinical trials. This may be because extinction learning appears to be context dependent and a change in context may result in a return of conditioned responding (i.e., renewal), although this has received only limited empirical examination. The current study used a 4-session laboratory analogue of CET to examine whether a change in context following 3 sessions of alcohol cue exposure with response prevention would result in renewal of conditioned responding. In addition, this study examined whether conducting extinction in multiple contexts would attenuate renewal of conditioned responding. In one-way between-subjects design, 73 heavy drinkers (71% men) were randomized to 3 conditions: (a) single context extinction (extinction to alcohol cues in the same context for 3 sessions followed by a context shift at the fourth session), (b) multiple context extinction (extinction to alcohol cues in different contexts each day for all 4 sessions), and (c) pseudoextinction control condition (exposure to neutral cues in the same context for 3 sessions followed by exposure to alcohol cues at the fourth session). The results revealed the predicted cue reactivity and extinction effects, but the hypotheses that a context shift would generate renewed cue reactivity and that multiple contexts would enhance extinction were not supported. Methodological aspects of the study and the need for parametric data on the context dependency of extinction to alcohol cues are discussed.
Alvarez, Walter; And Others
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)
Payne, C.; Haramundanis, K. L.
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).
Payne-Gaposchkin, C.; Haramundanis, K. L.
The progress made during the past six months in utilizing Celescope OAO-2 data in a study of extinction is reported along with conclusions drawn from each inquiry. Areas recommended for further investigation are indicated.
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.
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;…
Raup, D. M.
The results of a study of reversals of the earth's magnetic field over the past 165 Myr are presented. A stationary periodicity of 30 Myr emerges which predicts pulses of increased reversal activity centered at 10, 40, 70, . . . Myr before the present. The correlation between the reversal intensity and biological extinctions is examined, and a nontrivial discrepancy is found between the magnetic and extinction periodicity.
Novick, Vincent J.
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.
Sjouwerman, Rachel; Niehaus, Johanna; Lonsdorf, Tina B.
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
Podlesnik, Christopher A; Shahan, Timothy A
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.
Arce, Héctor G.; Goodman, Alyssa A.
We test the recently published all-sky reddening map of Schlegel, Finkbeiner, & Davis (hereafter SFD) using the extinction study of a region in the Taurus dark cloud complex by Arce & Goodman (hereafter AG). In their study, AG use four different techniques to measure the amount and structure of the extinction toward Taurus, and all four techniques agree very well. Thus, we believe that the AG results are a truthful representation of the extinction in the region and can be used to test the reliability of the SFD reddening map. The results of our test show that the SFD all-sky reddening map, which is based on data from COBE/DIRBE and IRAS/ISSA, overestimates the reddening by a factor of 1.3-1.5 in regions of smooth extinction with AV>0.5 mag. In some regions of steep extinction gradients, the SFD map underestimates the reddening value, probably because of its low spatial resolution. We expect that the astronomical community will be using the SFD reddening map extensively. We offer this Letter as a cautionary note about using the SFD map in regions of high extinction (AV>0.5 mag), since it might not be giving accurate reddening values there.
Hicks, Megan P; Wischerath, Kelly C; Lacrosse, Amber L; Olive, M Foster
Adult-generated neurons in the dentate gyrus (DG) of the hippocampus play a role in various forms of learning and memory. However, adult born neurons in the DG, while still at an immature stage, exhibit unique electrophysiological properties and are also functionally implicated in learning and memory processes. We investigated the effects of extinction of drug-seeking behavior on the formation of immature neurons in the DG as assessed by quantification of doublecortin (DCX) immunoreactivity. Rats were allowed to self-administer heroin (0.03 mg/kg/infusion) for 12 days and then subjected either to 10 days of extinction training or forced abstinence. We also examined extinction responding patterns following heroin self-administration in glial fibrillary acidic protein thymidine kinase (GFAP-tk) transgenic mice, which have been previously demonstrated to show reduced formation of immature and mature neurons in the DG following treatment with ganciclovir (GCV). We found that extinction training increased DCX immunoreactivity in the dorsal DG as compared with animals undergoing forced abstinence, and that GCV-treated GFAP-tk mice displayed impaired extinction learning as compared to saline-treated mice. Our results suggest that extinction of drug-seeking behavior increases the formation of immature neurons in the DG and that these neurons may play a functional role in extinction learning.
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
Worsley, T. R.; Kidder, D. L.
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
Orellana Barrera, Estefanía; Arias, Carlos; González, Felisa; Abate, Paula
The present study evaluated context-dependent learning under an operant conditioning procedure in infant rats. Preweanling rats were trained in context A during postnatal days (PDs) 16 and 17 to learn an appetitive operant conditioning task, employing milk chocolate as appetitive reinforcer. On PD18 the operant response was extinguished in context A, or in an alternative context B. The change from context A to B between acquisition and extinction did not affect the number of responses during extinction, but slightly modified the shape of the extinction curve. On PD19, a renewal test conducted in context A clearly showed ABA-renewal of the extinguished operant response. These results add to the body of evidence indicating that infants are able to acquire and retain contextual information, and support the notion that extinction during this ontogenetic period involves new learning.
Kehoe, E James; White, Natasha E
The mechanisms of extinction were examined by reducing the intensity of the unconditioned stimulus (US) after acquisition training to determine whether such reductions lie on a continuum with CS-alone extinction. The experiments revealed that reductions in US intensity yielded extinction-like effects. Specifically, there were proportional reductions in the daily mean level of responding across sessions. There were also persistent within-session declines and between-session increases of responding analogous to spontaneous recovery. Surprisingly, even when US intensity was held constant, within-session declines and between-session increases were apparent. The results are discussed with respect to possible contributions from unlearning, new learning, generalization decrement, and nonassociative loss, especially CS-specific attentional changes and CR-specific reactive inhibition.
Myers, Karyn M.; Ressler, Kerry J.; Davis, Michael
Fear extinction is defined as a decline in conditioned fear responses (CRs) following nonreinforced exposure to a feared conditioned stimulus (CS). Behavioral evidence indicates that extinction is a form of inhibitory learning: Extinguished fear responses reappear with the passage of time (spontaneous recovery), a shift of context (renewal), and unsignaled presentations of the unconditioned stimulus (reinstatement). However, there also is evidence to suggest that extinction is an “unlearning” process corresponding to depotentiation of potentiated synapses within the amygdala. Because depotentiation is induced more readily at short intervals following LTP induction and is not inducible at all at a sufficient delay, it may be that extinction initiated shortly following fear acquisition preferentially engages depotentiation/“unlearning,” whereas extinction initiated at longer delays recruits a different mechanism. We investigated this possibility through a series of behavioral experiments examining the recoverability of conditioned fear following extinction. Consistent with an inhibitory learning mechanism of extinction, rats extinguished 24–72 h following acquisition exhibited moderate to strong reinstatement, renewal, and spontaneous recovery. In contrast, and consistent with an erasure mechanism, rats extinguished 10 min to 1 h after acquisition exhibited little or no reinstatement, renewal, or spontaneous recovery. These data support a model in which different neural mechanisms are recruited depending on the temporal delay of fear extinction. PMID:16585797
Laricchiuta, Daniela; Centonze, Diego; Petrosini, Laura
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.
Laurent, Vincent; Westbrook, R Frederick
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 inhibition (experiment 1). Inactivation of the IL did not affect inhibition across the first extinction but disrupted its long-term retention. Inactivation of the IL impaired inhibition across the second extinction, and inactivation before or after this extinction impaired long-term retention (experiments 2 and 3). Inactivation of the IL before the retention test restored extinguished fear responses (experiment 4). These results show for the first time that neuronal activity in the PL is involved in the expression of fear responses but not in the learning that underlies long-term fear inhibition. They also confirm that the IL is involved in this inhibitory learning: Specifically, they show that the IL is critical for consolidation and retrieval of this inhibitory learning. The role of the IL is discussed in terms of a contemporary neural model of fear extinction.
Whittle, N; Maurer, V; Murphy, C; Rainer, J; Bindreither, D; Hauschild, M; Scharinger, A; Oberhauser, M; Keil, T; Brehm, C; Valovka, T; Striessnig, J; Singewald, N
Extinction-based exposure therapy is used to treat anxiety- and trauma-related disorders; however, there is the need to improve its limited efficacy in individuals with impaired fear extinction learning and to promote greater protection against return-of-fear phenomena. Here, using 129S1/SvImJ mice, which display impaired fear extinction acquisition and extinction consolidation, we revealed that persistent and context-independent rescue of deficient fear extinction in these mice was associated with enhanced expression of dopamine-related genes, such as dopamine D1 (Drd1a) and -D2 (Drd2) receptor genes in the medial prefrontal cortex (mPFC) and amygdala, but not hippocampus. Moreover, enhanced histone acetylation was observed in the promoter of the extinction-regulated Drd2 gene in the mPFC, revealing a potential gene-regulatory mechanism. Although enhancing histone acetylation, via administering the histone deacetylase (HDAC) inhibitor MS-275, does not induce fear reduction during extinction training, it promoted enduring and context-independent rescue of deficient fear extinction consolidation/retrieval once extinction learning was initiated as shown following a mild conditioning protocol. This was associated with enhanced histone acetylation in neurons of the mPFC and amygdala. Finally, as a proof-of-principle, mimicking enhanced dopaminergic signaling by L-dopa treatment rescued deficient fear extinction and co-administration of MS-275 rendered this effect enduring and context-independent. In summary, current data reveal that combining dopaminergic and epigenetic mechanisms is a promising strategy to improve exposure-based behavior therapy in extinction-impaired individuals by initiating the formation of an enduring and context-independent fear-inhibitory memory. PMID:27922638
Goodman, Jarid; Ressler, Reed L; Packard, Mark G
The present experiments investigated the involvement of N-methyl-d-aspartate (NMDA) receptors of the dorsolateral striatum (DLS) in consolidation of extinction in a habit memory task. Adult male Long-Evans rats were initially trained in a food-reinforced response learning version of a plus-maze task and were subsequently given extinction training in which the food was removed from the maze. In experiment 1, immediately after the first day of extinction training, rats received bilateral intra-DLS injections of the NMDA receptor antagonist 2-amino-5-phosphonopentanoic acid (AP5; 2µg/side) or physiological saline. In experiment 2, immediately following the first day of extinction training, animals were given intra-DLS injections of NMDA receptor partial agonist d-cycloserine (DCS; 10 or 20µg/side) or saline. In both experiments, the number of perseverative trials (a trial in which a rat made the same previously reinforced body-turn response) and latency to reach the previously correct food well were used as measures of extinction behavior. Results indicated that post-training intra-DLS injections of AP5 impaired extinction. In contrast, post-training intra-DLS infusions of DCS (20µg) enhanced extinction. Intra-DLS administration of AP5 or DCS given two hours after extinction training did not influence extinction of response learning, indicating that immediate post-training administration of AP5 and DCS specifically influenced consolidation of the extinction memory. The present results indicate a critical role for DLS NMDA receptors in modulating extinction of habit memory and may be relevant to developing therapeutic approaches to combat the maladaptive habits observed in human psychopathologies in which DLS-dependent memory has been implicated (e.g. drug addiction and relapse and obsessive compulsive disorder).
Sloan, R. E.
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.
van den Akker, Karolien; Havermans, Remco C; Bouton, Mark E; Jansen, Anita
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.
Cruz, Emmanuel; Soler-Cedeño, Omar; Negrón, Geovanny; Criado-Marrero, Marangelie; Chompré, Gladys
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
Cruz, Emmanuel; Soler-Cedeño, Omar; Negrón, Geovanny; Criado-Marrero, Marangelie; Chompré, Gladys; Porter, James T
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.
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
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.
Stothers, Richard B.
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.
Morgan, W. Jason
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.
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.
Manwell, Laurie A; Satvat, Elham; Lang, Stefan T; Allen, Craig P; Leri, Francesco; Parker, Linda A
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.
Voigt, Robin M; Herrold, Amy A; Napier, T Celeste
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.
Ponnusamy, Ravikumar; Zhuravka, Irina; Poulos, Andrew M.; Shobe, Justin; Merjanian, Michael; Huang, Jeannie; Wolvek, David; O’Neill, Pia-Kelsey; Fanselow, Michael S.
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
Kaplan, Gary B; Heinrichs, Stephen C; Carey, Robert J
Clinical interventions which produce cue and contextual extinction learning can reduce craving and relapse in substance abuse and inhibit conditioned fear responses in anxiety disorders. In both types of disorders, classical conditioning links unconditioned drug or fear responses to associated contextual cues and result in enduring pathological responses to multiple stimuli. Extinction therapy countermeasures seek to reduce conditioned responses using a set of techniques in which patients are repeatedly exposed to conditioned appetitive or aversive stimuli using imaginal imagery, in vivo exposure, or written scripts. Such interventions allow patients to rehearse more adaptive responses to conditioned stimuli. The ultimate goal of these interventions, extinction of the original conditioned response, is a new learning process that results in a decrease in frequency or intensity of conditioned responses to drug or fear cues. This review explores extinction approaches in conditioned drug reward and fear responses. The behavioral, neuroanatomical and neurochemical mechanisms of conditioned reward and fear responses and their extinction are derived from our understanding of the animal literature. Extensive neuroscience research shows that even though many mechanisms differ in conditioned fear and reward, converging prefrontal cortical glutamatergic pathways underlie extinction learning. Efficacy of pharmacological and behavioral treatment approaches in addiction and anxiety disorders may be optimized by enhancing extinction and weakening the bond between the original conditioned stimuli and conditioned responses. Adjunctive pharmacotherapy approaches using agents which alter glutamate or γ-aminobutyric acid signaling or epigenetic mechanisms in prefrontal cortical pathways can enhance extinction learning. A comparative study of extinction processes and its neural mechanisms can be translated into more effective behavioral and pharmacological treatment approaches in
Valenzuela-Harrington, Mauricio; Castillo, Irene; Díaz, Corín; Alés, Inés; Rodríguez-Moreno, Antonio
In agriculture, organophosphates are frequently used as insecticides and pesticides. These compounds decrease acetylcholine esterase (AChE) activity, thereby provoking an accumulation of the neurotransmitter acetylcholine at synapses and resulting in the over-stimulation of acetylcholine receptors. Using trace paradigms, we investigated the effects of dimethoate, a widely used organophosphate insecticide, on the classical conditioning of eyelid responses, a hippocampal-dependent mouse model of associative learning. Mice were conditioned with a trace shock-SHOCK paradigm having first implanted stimulating electrodes in the supraorbitary nerve and recording electrodes in the ipsilateral orbicularis oculi muscle. When these mice were injected with dimethoate (5, 20, 50mg/kg/day) they were capable of acquiring associative learning, and the latency and amplitude of their unconditioned eyelid responses were unaffected by the administration of the pesticide. However, dimethoate administration led to the rapid extinction of conditioned responses, suggesting that this organophosphate accelerates the extinction of this form of associative learning. Analysis of the motor function of these mice using the rotarod performance test revealed that motor function and performance clearly deteriorated following dimethoate administration, with no improvements over the following 4 days. Together these findings indicate that dimethoate accelerates the extinction of acquired conditioned responses, affecting associative learning and memory, and it impairs motor function and performance in mice.
Hughes, Stephen W.; Cowley, Michael; Powell, Sean; Carroll, Joshua
An experiment is described that enables students to understand the properties of atmospheric extinction due to Rayleigh scattering. The experiment requires the use of red, green and blue lasers attached to a travelling microscope or similar device. The laser beams are passed through an artificial atmosphere, made from milky water, at varying depths, before impinging on either a light meter or a photodiode integral to a Picotech Dr. DAQ ADC. A plot of measured spectral intensity verses depth reveals the contribution Rayleigh scattering has to the extinction coefficient. For the experiment with the light meter, the extinction coefficients for red, green and blue light in the milky sample of water were 0.27, 0.36 and 0.47 cm-1 respectively and 0.032, 0.037 and 0.092 cm-1 for the Picotech Dr. DAQ ADC.
MacPhee, Ross D. E.; Greenwood, Alex D.
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
Macphee, Ross D E; Greenwood, Alex D
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.
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.
Jordan, Wesley P; Todd, Travis P; Bucci, David J; Leaton, Robert N
In two conditioned suppression experiments with a latent inhibition (LI) design, we measured the habituation of rats in preexposure, their LI during conditioning, and then extinction over days. In the first experiment, lick suppression, the preexposed group (PE) showed a significant initial unconditioned response (UR) to the target stimulus and significant long-term habituation (LTH) of that response over days. The significant difference between the PE and nonpreexposed (NPE) groups on the first conditioning trial was due solely to the difference in their URs to the conditioned stimulus (CS)-a habituated response (PE) and an unhabituated response (NPE). In the second experiment, bar-press suppression, little UR to the target stimulus was apparent during preexposure, and no detectable LTH. Thus, there was no difference between the PE and NPE groups on the first conditioning trial. Whether the UR to the CS confounds the interpretation of LI (Exp. 1) or not (Exp. 2) can only be known if the UR is measured. In both experiments, LI was observed in acquisition. Also in both experiments, rats that were preexposed and then conditioned to asymptote were significantly more resistant to extinction than were the rats not preexposed. This result contrasts with the consistently reported finding that preexposure either produces less resistance to extinction or has no effect on extinction. The effect of stimulus preexposure survived conditioning to asymptote and was reflected directly in extinction. These two experiments provide a cautionary procedural note for LI experiments and have shown an unexpected extinction effect that may provide new insights into the interpretation of LI.
Veresoglou, Stavros D; Halley, John M; Rillig, Matthias C
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.
Veresoglou, Stavros D.; Halley, John M.; Rillig, Matthias C.
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
Cameron, A. G. W.
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.
Wickramasinghe, N. C.; Jazbi, B.; Hoyle, F.
The rigorous Kerker-Matijevic formulas for light scattering by coaxial double cylinders are used to calculate the extinction properties of hollow organic grains. A size distribution of such particles together with iron whiskers of radii 0.01 micron, silica spheres of radius 0.03 micron and free aromatic molecular clusters comprised of 50-100 atoms yield excellent agreement with data on the extinction of starlight. The mass ratios of silica to organics and of iron to organics are in good accord with cosmic abundance constraints.
Katyal, N.; Gupta, R.; Vaidya, D. B.
A composite dust grain model which simultaneously explains the observed interstellar extinction, polarization, IR emission and the abundance constraints, is required. We present a composite grain model, which is made up of a host silicate oblate spheroid and graphite inclusions. The interstellar extinction curve is evaluated in the spectral region 3.4-0.1 μm using the extinction efficiencies of composite spheroidal grains for three axial ratios. Extinction curves are computed using the discrete dipole approximation (DDA). The model curves are subsequently compared with the average observed interstellar extinction curve and with an extinction curve derived from the IUE catalogue data.
Fitzgerald, Paul J; Giustino, Thomas F; Seemann, Jocelyn R; Maren, Stephen
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.
Leising, M. D.
Gamma ray spectroscopy holds great promise for probing nucleosynthesis in individual nucleosynthesis events, via observations of short-lived radioactivity, and for measuring global galactic nucleosynthesis today with detections of longer-lived radioactivity. Many of the astrophysical issues addressed by these observations are precisely those that must be understood in order to interpret observations of extinct radioactivity in meteorites. It was somewhat surprising that the former case was realized first for a Type II supernova, when both 56Co  and 57Co  were detected in SN 1987A. These provide unprecedented constraints on models of Type II explosions. Live 26Al in the galaxy might come from Type II supernovae and their progenitors, and if this is eventually shown to be the case, can constrain massive star evolution, supernova nucleosynthesis, the galactic Type II supernova rate, and even models of the chemical evolution of the galaxy . Titanium-44 is produced primarily in the alpha-rich freezeout from nuclear statistical equilibrium, possibly in Type Ia  and almost certainly in Type II supernovae . The galactic recurrence time of these events is comparable to the 44Ti lifetime, so we expect to be able to see at most a few otherwise unseen 44Ti remnants at any given time. No such remnants have been detected yet . Very simple arguments lead to the expectation that about 4 x 10^-4 M(sub)solar mass of 44Ca are produced per century. The product of the supernova frequency times the 44Ti yield per event must equal this number. Even assuming that only the latest event would be seen, rates in excess of 2 century^-1 are ruled out at >=99% confidence by the gamma ray limits. Only rates less than 0.3 century^-1 are acceptable at >5% confidence, and this means that the yield per event must be >10^-3 M(sub)solar mass to produce the requisite 44Ca. Rates this low are incompatible with current estimates for Type II supernovae and yields this high are also very
Baker, Kathryn D.; McNally, Gavan P.; Richardson, Rick
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…
Gordon, Sheldon P.
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,…
Furini, Cristiane R G; Behling, Jonny A K; Zinn, Carolina G; Zanini, Mara Lise; Assis Brasil, Eduardo; Pereira, Luiza Doro; Izquierdo, Ivan; de Carvalho Myskiw, Jociane
Extinction is defined as the learned inhibition of retrieval and is the mainstay of exposure therapy, which is widely used to treat drug addiction, phobias and fear disorders. The psychostimulant, methylphenidate (MPH) is known to increase extracellular levels of noradrenaline and dopamine by blocking their reuptake and studies have demonstrated that MPH can modulate hippocampal physiology and/or functions including long-term potentiation (LTP), learning and memory. However, the influence of MPH on fear extinction memory has been insufficiently studied. Here we investigate the effect of MPH infused into the CA1 region of the hippocampus on extinction memory in animals normally incapable of showing contextual fear conditioning (CFC) extinction because of weak training, and the possible mechanisms through which it acts during this process. For this, male Wistar rats with infusion cannulae stereotaxically implanted in the CA1 region were submitted to a weak extinction protocol in a CFC apparatus. Animals that received intra-CA1 infusion of MPH (12.5μg/side) 20min before the extinction training (Ext Tr) expressed less freezing behavior than Veh-treated animals during both Ext Tr and extinction retention Test (Ext Test). Additionally, the administration of MPH+Timolol (1μg/side) or MPH+SCH23390 (1.5μg/side) intra-CA1 20min before the Ext Tr blocked the enhancing effect of the MPH on extinction learning. These results suggest that MPH in the CA1 region of the hippocampus is able to induce the consolidation of extinction memory and this process occurs through both β-adrenergic and D1/D5 dopaminergic receptors.
The purpose of the study was to compare the extinctions calculated from data obtained with the Ames Wire Impactor to extinctions measured with the SAGE H satellite system. The comparison was intended to serve as a validation of the extinctions obtained using the wire impactor data. It was felt that if the extinctions obtained by the two diverse methods agreed well, it would be an indication that the number densities measured on the wires were correct.
Kerr, R A
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.
Sotres-Bayon, Francisco; Bush, David E A; LeDoux, Joseph E
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.
Li, Yuzhe; Nakae, Ken; Ishii, Shin; Naoki, Honda
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
Morrison, Filomene G; Ressler, Kerry J
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.
Morrison, Filomene G.; Ressler, Kerry J.
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
Zbukvic, Isabel C; Ganella, Despina E; Perry, Christina J; Madsen, Heather B; Bye, Christopher R; Lawrence, Andrew J; Kim, Jee Hyun
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.
Anastasio, Thomas J.
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
Jansen, Anita; Schyns, Ghislaine; Bongers, Peggy; van den Akker, Karolien
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.
Bowers, Mallory E.; Xia, Bing; Carreiro, Samantha; Ressler, Kerry J.
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…
Marshall, Rebecca Shisler; Basilakos, Alexandra; Love-Myers, Kim
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)…
Leslie, Julian C; Shaw, David; Gregg, Gillian; McCormick, Nichola; Reynolds, David S; Dawson, Gerard R
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.
Whittle, Nigel; Schmuckermair, Claudia; Gunduz Cinar, Ozge; Hauschild, Markus; Ferraguti, Francesco; Holmes, Andrew; Singewald, Nicolas
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'.
Shechner, Tomer; Hong, Melanie; Britton, Jennifer C; Pine, Daniel S; Fox, Nathan A
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.
Walker, Robert S.; Kesler, Dylan C.; Hill, Kim R.
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
role of gonadal hormones in the regulation of Pavlovian fear conditioning and its extinction. Pavlovian fear conditioning and its extinction serve...learning in Pavlovian fear conditioning involves training with the presentation of an innocuous stimulus (the conditioned stimulus – CS) that is associated...GD, Schlinger BA, Fanselow MS (1998) Testicular hormones do not regulate sexually dimorphic Pavlovian fear conditioning or perforant- path long-term
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
Ross, Alistair; Leathwood, Carole
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…
Hoiberg, Karen Bush; Sharp, Janet; Hodgson, Ted; Colbert, Jim
This article describes how a group of fifth-grade mathematics students measured irregularly shaped objects using geometric probability theory. After learning how to apply a ratio procedure to find the areas of familiar shapes, students extended the strategy for use with irregularly shaped objects, in this case, leaves. (Contains 2 tables and 8…
Careaga, Mariella Bodemeier Loayza; Girardi, Carlos Eduardo Neves; Suchecki, Deborah
Careaga MBL, Girardi CEN, Suchecki D. Understanding posttraumatic stress disorder through fear conditioning, extinction and reconsolidation. NEUROSCI BIOBEHAV REV -Posttraumatic stress disorder (PTSD) is a psychopathology characterized by exacerbation of fear response. A dysregulated fear response may be explained by dysfunctional learning and memory, a hypothesis that was proposed decades ago. A key component of PTSD is fear conditioning and the study of this phenomenon in laboratory has expanded the understanding of the underlying neurobiological changes in PTSD. Furthermore, traumatic memories are strongly present even years after the trauma and maintenance of this memory is usually related to behavioral and physiological maladaptive responses. Persistence of traumatic memory may be explained by a dysregulation of two memory processes: extinction and reconsolidation. The former may explain the over-expression of fear responses as an imbalance between traumatic and extinction memory. The latter, in turn, explains the maintenance of fear responses as a result of enhancing trauma-related memories. Thus, this review will discuss the importance of fear conditioning for the establishment of PTSD and how failure in extinction or abnormal reconsolidation may contribute to the maintenance of fear response overtime.
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".
Donn, B.; Hecht, J. H.; Helfer, H. L.; Wolf, J.; Pipher, J. L.
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.
The purpose of the study was to compare the extinctions calculated from data obtained with the Ames Wire Impactor to extinctions measured with the SAGE 11 satellite system. The comparison was intended to serve as a validation of the extinctions obtained using the wire impactor data. It was felt that if the extinctions obtained by the two diverse methods agreed well, it would be an indication that the number densities measured on the wires were correct. Tables and charts are presented to show the extinction values from the two different methods.
Alvarez, Ruben P.; Johnson, Linda; Grillon, Christian
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 by examining the context specificity of short-delay extinction in an ABA renewal procedure using virtual reality environments. A second objective was to examine whether renewal, if any, would be influenced by context conditioning. Subjects underwent differential aversive conditioning in virtual context A, which was immediately followed by extinction in virtual context B. Extinction was followed by tests of renewal in context A and B, with the order counterbalanced across subjects. Results showed that extinction was context dependent. Evidence for renewal was established using fear-potentiated startle as well as skin conductance and fear ratings. In addition, although contextual anxiety was greater in the acquisition context than in the extinction context during renewal, as assessed with startle, context conditioning did not influence the renewal effect. These data do not support the view that extinction conducted shortly after acquisition is context independent. Hence, they do not provide evidence that extinction can lead to erasure of a fear memory established via Pavlovian conditioning. PMID:17412963
Liddie, Shervin; Anderson, Karen L; Paz, Andres; Itzhak, Yossef
Several phosphodiesterase inhibitors (PDEis) improve cognition, suggesting that an increase in brain cAMP and cGMP facilitates learning and memory. Since extinction of drug-seeking behavior requires associative learning, consolidation and formation of new memory, the present study investigated the efficacy of three different PDEis in the extinction of cocaine-induced conditioned place preference (CPP) in B6129S mice. Mice were conditioned by escalating doses of cocaine which was resistant to extinction by free exploration. Immediately following each extinction session mice received (a) saline/vehicle, (b) rolipram (PDE4 inhibitor), (c) BAY-73-6691 (PDE9 inhibitor) or (d) papaverine (PDE10A inhibitor). Mice that received saline/vehicle during extinction training showed no reduction in CPP for >10 days. BAY-73-6691 (a) dose-dependently increased cGMP in hippocampus and amygdala, (b) significantly facilitated extinction and (c) diminished the reinstatement of cocaine CPP. Rolipram, which selectively increased brain cAMP levels, and papaverine which caused increases in both cAMP and cGMP levels, had no significant effect on the extinction of cocaine CPP. The results suggest that increase in hippocampal and amygdalar cGMP levels via blockade of PDE9 has a prominent role in the consolidation of extinction learning.
Keller, Samantha M; Schreiber, William B; Stanfield, Briana R; Knox, Dayan
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.
Vamosi, Jana C; Vamosi, Steven M
The latitudinal biodiversity gradient remains one of the most widely recognized yet puzzling patterns in nature. Presently, the high level of extinction of tropical species, referred to as the "tropical biodiversity crisis", has the potential to erode this pattern. While the connection between species richness, extinction, and speciation has long intrigued biologists, these interactions have experienced increased poignancy due to their relevancy to where we should concentrate our conservation efforts. Natural extinction is a phenomenon thought to have its own latitudinal gradient, with lower extinction rates in the tropics being reported in beetles, birds, mammals, and bivalves. Processes that have buffered ecosystems from high extinction rates in the past may also buffer ecosystems against disturbance of anthropogenic origin. While potential parallels between historical and present-day extinction patterns have been acknowledged, they remain only superficially explored and plant extinction patterns have been particularly neglected. Studies on the disappearances of animal species have reached conflicting conclusions, with the rate of extinction appearing either higher or lower in species richness hotspots. Our global study of extinction risk in vascular plants finds disproportionately higher extinction risk in tropical countries, even when indicators of human pressure (GDP, population density, forest cover change) are taken into account. Our results are at odds with the notion that the tropics represent a museum of plant biodiversity (places of historically lowered extinction) and we discuss mechanisms that may reconcile this apparent contradiction.
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.
Roy, Kaustuv; Hunt, Gene; Jablonski, David
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.
Sheehan, P. M.; Coorough, P. J.
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.
Raup, D. M.
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.
Bosman, Renske C.; Borg, Charmaine; de Jong, Peter J.
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
Claassen, J; Mazilescu, L; Thieme, A; Bracha, V; Timmann, D
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.
Killeen, Peter R; Sanabria, Federico; Dolgov, Igor
Pigeons responded to intermittently reinforced classical conditioning trials with erratic bouts of responding to the conditioned stimulus. Responding depended on whether the prior trial contained a peck, food, or both. A linear persistence-learning model moved pigeons into and out of a response state, and a Weibull distribution for number of within-trial responses governed in-state pecking. Variations of trial and intertrial durations caused correlated changes in rate and probability of responding and in model parameters. A novel prediction--in the protracted absence of food, response rates can plateau above zero--was validated. The model predicted smooth acquisition functions when instantiated with the probability of food but a more accurate jagged learning curve when instantiated with trial-to-trial records of reinforcement. The Skinnerian parameter was dominant only when food could be accelerated or delayed by pecking. These experiments provide a framework for trial-by-trial accounts of conditioning and extinction that increases the information available from the data, permitting such accounts to comment more definitively on complex contemporary models of momentum and conditioning.
Killeen, Peter R.; Sanabria, Federico; Dolgov, Igor
Pigeons responded to intermittently reinforced classical conditioning trials with erratic bouts of responding to the CS. Responding depended on whether the prior trial contained a peck, food, or both. A linear-persistence/learning model moved animals into and out of a response state, and a Weibull distribution for number of within-trial responses governed in-state pecking. Variations of trial and inter-trial durations caused correlated changes in rate and probability of responding, and model parameters. A novel prediction—in the protracted absence of food, response rates can plateau above zero—was validated. The model predicted smooth acquisition functions when instantiated with the probability of food, but a more accurate jagged learning curve when instantiated with trial-to-trial records of reinforcement. The Skinnerian parameter was dominant only when food could be accelerated or delayed by pecking. These experiments provide a framework for trial-by-trial accounts of conditioning and extinction that increases the information available from the data, permitting them to comment more definitively on complex contemporary models of momentum and conditioning. PMID:19839699
Sandusky, Leslie A; Flint, Robert W; McNay, Ewan C
The effect of cycloheximide (CXM), a protein synthesis inhibitor, on memory reconsolidation and extinction was explored in rats using a model of post-traumatic stress. Forty-two animals were exposed to predator stress followed by 1, 2, or 4 extinction trials. Saline or CXM (1 mg/kg) was administered following the last extinction trial and anxiety was measured in the elevated-plus maze (EPM) seventy-two hours later. Saline control animals exhibited elevated anxiety levels in comparison to a no stress control group. Cycloheximide appeared to maintain stress-induced anxiety responses, which otherwise declined with repeated extinction trials in the saline control groups. These findings suggest that cycloheximide may have induced amnesia for extinction, leaving the target memory of the predatory stress intact resulting in elevated levels of anxiety. The relationships between de novo protein synthesis and reconsolidation of anxiety-related memories following extinction trials may be more complex than originally thought.
Whittle, Nigel; Hauschild, Markus; Lubec, Gert; Holmes, Andrew; Singewald, Nicolas
Fear extinction is impaired in neuropsychiatric disorders, including posttraumatic stress disorder. Identifying drugs that facilitate fear extinction in animal models provides leads for novel pharmacological treatments for these disorders. Zinc (Zn) is expressed in neurons in a cortico-amygdala circuit mediating fear extinction, and modulates neurotransmitter systems regulating extinction. We previously found that the 129S1/SvImJ mouse strain (S1) exhibited a profound impairment in fear extinction, coupled with abnormalities in the activation of the extinction circuit. Here, we tested the role of Zn in fear extinction in S1 and C57BL/6N reference strain (B6) by feeding the mice a Zn-restricted diet (ZnR) and testing for fear extinction, as well as neuronal activation of the extinction circuit via quantification of the immediate-early genes c-Fos and Zif268. Results showed that (preconditioning or postconditioning) ZnR completely rescued deficient extinction learning and long-term extinction retrieval in S1 and expedited extinction learning in B6, without affecting fear acquisition or fear expression. The extinction-facilitating effects of ZnR were associated with the normalization of Zif268 and/or c-Fos expression in cortico-amygdala regions of S1. Specifically, ZnR increased activity in infralimbic cortex, lateral and basolateral amygdala nuclei, and lateral central amygdala nucleus, and decreased activity in prelimbic and insular cortices and medial central amygdala nucleus. ZnR also increased activation in the main intercalated nucleus and decreased activation of the medial paracapsular intercalated mass in S1. Our findings reveal a novel role for Zn in fear extinction and further support the utility of the S1 model for identifying extinction facilitating drugs.
Griffin, Kimberly; Cavalier, Sheridan; McIntyre, Christa K.
Vagus nerve stimulation (VNS) enhances the consolidation of extinction of conditioned fear. High frequency stimulation of the infralimbic cortex (IL) produces long-term potentiation in the basolateral amygdala (BLA) in rats given VNS-paired extinction training, whereas the same stimulation produces long-term depression in sham-treated rats. The present study investigated the state of synaptic plasticity-associated proteins in the BLA that could be responsible for this shift. Male Sprague-Dawley rats were separated into 4 groups: auditory fear conditioning only (fear-conditioned); fear conditioning + 20 extinction trials (extended-extinction); fear conditioning + 4 extinction trials paired with sham stimulation (sham-extinction); fear conditioning + 4 extinction trials paired with VNS (VNS-extinction). Freezing was significantly reduced in extended-extinction and VNS-extinction rats. Western blots were used to quantify expression and phosphorylation state of synaptic plasticity-associated proteins such as Arc, CaMKII, ERK, PKA, and AMPA and NMDA receptors. Results show significant increases in GluN2B expression and phosphorylated CaMKII in BLA samples from VNS- and extended-extinction rats. Arc expression was significantly reduced in VNS-extinction rats compared to all groups. Administration of the GluN2B antagonist ifenprodil immediately after fear extinction training blocked consolidation of extinction learning. Results indicate a role for BLA CaMKII-induced GluN2B expression and reduced Arc protein in VNS-enhanced extinction. PMID:27957346
Giustino, Thomas F; Fitzgerald, Paul J; Maren, Stephen
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.
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)
Kavehpour, H. Pirouz; Shirazi, Elika T.; Alizadeh-Birjandi, Elaheh
Ice adhesion and excessive accumulation on exposed structures and equipment are well known to cause serious problems in cold-climate regions; therefore, the development of coatings that can resist icing can solve many challenges in various areas of industry. This work was inspired by nature and ice-resistivity and superhydrophobicity of plants leaves. Kale is an example of a plant that can be harvested in winter. It shows superhydrophobic behavior, which is normally known as an advantage for cleaning the leaves, but we were able to show that its surface structure and high contact angle of water drops on kale leaves could delay the ice formation process making it a good candidate for an ice-repellent coating. We have performed in-depth experimental analyses on how different plants can prevent icing, and contact angle measurements and scanning electron microscopy (SEM) of the leaves were taken to further mimic their surface morphology.
Raup, D. M.
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.
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.
Raup, D. M.
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
Kearns, David N; Tunstall, Brendan J; Marks, Katherine R; Weiss, Stanley J
Previous studies have suggested that the effects of extinction are response-specific. The present study investigated whether an extinction treatment that eliminated goal tracking elicited by an appetitive conditioned stimulus (CS) would also eliminate the conditioned reinforcing effects of that CS. Rats were first trained on a goal-tracking procedure in which an auditory CS was paired with a food unconditioned stimulus. Animals learned to approach the location where the food was delivered. In a subsequent phase, rats in one group received extinction training that eliminated the goal-tracking elicited by the CS. Rats in the other group did not experience extinction of the food-paired CS. Then, both groups received a test for conditioned reinforcement in which leverpresses resulted in the brief presentation of the stimulus previously paired with food. This stimulus did not act as a conditioned reinforcer in the group that had been subjected to extinction training, but did serve as a conditioned reinforcer in the group that did not experience extinction. These results indicate that the effects of extinction generalize from the approach-eliciting to the conditioned reinforcing effects of an appetitive CS.
Li, Lin; Boddul, Sanjay V; Patil, Sudarshan S; Zheng, Jun-Fang; An, Gunyong; Höger, Harald; Lubec, Gert
Studying fear extinction is a major topic in neuroscience. No information on systematic studies on the linkage of contextual fear conditioning (cFC) with hippocampal protein levels is available and we were therefore interested in protein differences between animals with poor and good extinction. cFC was carried out in C57BL/6J mice, hippocampi were taken and proteins were run on two-dimensional gel electrophoresis with subsequent quantification of protein spots. In-gel digestion with trypsin and identification by ion trap MS/MS (high-capacity ion trap) was used for the identification of significantly different hippocampal proteins between mice with good and poor performance of extinction. Signaling protein ras-related protein rab-7A and septin 8 levels were significantly higher in hippocampus of poor extinguishers, whereas ubiquitin carboxyterminal hydrolase isozyme L1 showed higher levels in animals with good extinction performance. A series of additional proteins showed significantly different levels between groups but the abovementioned were confirmed by immunoblotting. The abovementioned proteins have never been reported to be linked to extinction, memory, or learning and herein evidence for the involvement of several proteins in extinction mechanism as well as probably representing pharmaceutical targets is provided. Moreover, it is intriguing to demonstrate the differences between good and poor extinction performance at the protein level.
Flores, África; Valls-Comamala, Victòria; Costa, Giulia; Saravia, Rocío; Maldonado, Rafael; Berrendero, Fernando
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.
Sunsay, Ceyhun; Rebec, George V
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.
Baldi, Elisabetta; Bucherelli, Corrado
During contextual fear conditioning a rat learns a temporal contiguity association between the exposition to a previously neutral context (CS) and an aversive unconditioned stimulus (US) as a footshock. This condition determines in the rat the freezing reaction during the subsequent re-exposition to the context. Potentially the re-exposition without US presentation initiates two opposing and competing processes: reconsolidation and extinction. Reconsolidation process re-stabilizes and strengthens the original memory and it is initiated by a brief re-exposure to context. Instead the extinction process leads to the decrease of the expression of the original memory and it is triggered by prolonged re-exposure to the context. Here we analyzed the entorhinal cortex (ENT) participation in contextual fear conditioning reconsolidation and extinction. The rats were trained in contextual fear conditioning and 24h later they were subjected either to a brief (2 min) reactivation session or to a prolonged (120 min) re-exposition to context to induce extinction of the contextual fear memory. Immediately after the reactivation or the extinction session, the animals were submitted to bilateral ENT TTX inactivation. Memory retention was assessed as conditioned freezing duration measured 72 h after TTX administration. The results showed that ENT inactivation both after reactivation and extinction session was followed by contextual freezing retention impairment. Thus, the present findings point out that ENT is involved in contextual fear memory reconsolidation and extinction. This neural structure might be part of parallel circuits underlying two phases of contextual fear memory processing.
Crossman, Angela M.; Sullivan, Margaret Wolan; Hitchcock, Daniel F.; Lewis, Michael
Persistence of instrumental responding and negative facial expressions in response to repeated goal blockage was studied in 53 4-month-old infants. All participants experienced 2 sessions comprising baseline (no stimulation), contingency (stimulation resulting from infant action), and extinction (no stimulation) on consecutive days. Performance criteria identified 2 groups of infants, those who learned in Session 1 (Learning Group 1) and those who learned in Session 2 (Learning Group 2). Individual differences in instrumental responses and facial expression during extinction were compared as a function of learning group. Across sessions, the repetition of extinction for Learning Group 1 was associated with both a persistent instrumental response and anger expressions. The level of instrumental response and anger expression was equivalent to that observed for Learning Group 2 but only in Session 2, the day on which that group learned. Sadness and anger/sadness blended expressions were initially more common in Learning Group 2, but these expressions were attenuated given another exposure to the contingency in Session 2. Implications for the relations among infant emotion, cognition, and behavior are discussed. PMID:19186920
Warren, Brandon L.; Mendoza, Michael P.; Cruz, Fabio C.; Leao, Rodrigo M.; Caprioli, Daniele; Rubio, F. Javier; Whitaker, Leslie R.; McPherson, Kylie B.; Bossert, Jennifer M.; Shaham, Yavin
In operant learning, initial reward-associated memories are thought to be distinct from subsequent extinction-associated memories. Memories formed during operant learning are thought to be stored in “neuronal ensembles.” Thus, we hypothesize that different neuronal ensembles encode reward- and extinction-associated memories. Here, we examined prefrontal cortex neuronal ensembles involved in the recall of reward and extinction memories of food self-administration. We first trained rats to lever press for palatable food pellets for 7 d (1 h/d) and then exposed them to 0, 2, or 7 daily extinction sessions in which lever presses were not reinforced. Twenty-four hours after the last training or extinction session, we exposed the rats to either a short 15 min extinction test session or left them in their homecage (a control condition). We found maximal Fos (a neuronal activity marker) immunoreactivity in the ventral medial prefrontal cortex of rats that previously received 2 extinction sessions, suggesting that neuronal ensembles in this area encode extinction memories. We then used the Daun02 inactivation procedure to selectively disrupt ventral medial prefrontal cortex neuronal ensembles that were activated during the 15 min extinction session following 0 (no extinction) or 2 prior extinction sessions to determine the effects of inactivating the putative food reward and extinction ensembles, respectively, on subsequent nonreinforced food seeking 2 d later. Inactivation of the food reward ensembles decreased food seeking, whereas inactivation of the extinction ensembles increased food seeking. Our results indicate that distinct neuronal ensembles encoding operant reward and extinction memories intermingle within the same cortical area. SIGNIFICANCE STATEMENT A current popular hypothesis is that neuronal ensembles in different prefrontal cortex areas control reward-associated versus extinction-associated memories: the dorsal medial prefrontal cortex (mPFC) promotes
Dibbets, Pauline; van den Broek, Anne; Evers, Elisabeth A T
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.
Zlomuzica, Armin; Preusser, Friederike; Schneider, Silvia; Margraf, Jürgen
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
Sierra-Mercado, Demetrio; McAllister, Lauren M; Lee, Christopher C H; Milad, Mohammed R; Eskandar, Emad N; Whalen, Michael J
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.
Holmes, Nathan M; Westbrook, R Frederick
Three experiments used an ABA renewal paradigm to study deepening of response loss produced by extinction of reinstated or ABC renewed fear responses. In Experiment 1, rats were trained with two stimuli, S1 and S2, in context A and extinguished to S1 in context B and S2 in context C, shocked in B but not in C, and subjected to additional extinction of S1 in B and S2 in C. Rats froze less to S1 than S2 when subsequently tested in A. In Experiments 2 and 3, following training of S1 and S2 in A, one group received extinction of S1 in B and S2 in C followed by extinction of S1 in C and S2 in B. This group froze less to S1 in A or to S2 in a novel context, D, than a group always extinguished to S1 in B and S2 in C or a group extinguished to both S1 and S2 in B and C. These results show that additional extinction of a conditioned stimulus (conditional stimulus [CS]) exhibiting either reinstatement or ABC renewal renders that CS resistant to ABA renewal. They are consistent with theories that allow a role for context in extinction learning and that use error-correction mechanisms to update this learning.
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.
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
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.
Wu, Y. P.; Cheng, J. X.; Liu, X. X.; Wang, H. X.; Zhao, F. T.; Wen, W. W.
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.
Witnauer, James E; Miller, Ralph R
After many target stimulus (X)-unconditioned stimulus (US) pairings, further conditioning of X in the presence of another well-established signal for the US (A) disrupts X's behavioral control. Some researchers have argued that the mechanism underlying this so-called overexpectation effect is similar to that underlying extinction (a reduction in X's behavioral control due to X-alone presentations). Three conditioned suppression experiments with rats as subjects compared overexpectation and extinction. Experiment 1 replicated the basic overexpectation effect by showing that A disrupts responding to X more than does a previously neutral stimulus. Experiment 2 found that posttraining context exposure disrupts extinction but not overexpectation. Experiment 3 suggested that overexpectation and extinction are differentially sensitive to the effects of overtraining (compound reinforced or nonreinforced, respectively), such that extinction is enhanced by increases in the amount of nonreinforced trials and overexpectation is unaffected. These results are inconsistent with the view that overexpectation and extinction are driven by a common mechanism.
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…
Janak, Patricia H; Bowers, M Scott; Corbit, Laura H
Drug abstinence is frequently compromised when addicted individuals are re-exposed to environmental stimuli previously associated with drug use. Research with human addicts and in animal models has demonstrated that extinction learning (non-reinforced cue-exposure) can reduce the capacity of such stimuli to induce relapse, yet extinction therapies have limited long-term success under real-world conditions (Bouton, 2002; O'Brien, 2008). We hypothesized that enhancing extinction would reduce the later ability of drug-predictive cues to precipitate drug-seeking behavior. We, therefore, tested whether compound stimulus presentation and pharmacological treatments that augment noradrenergic activity (atomoxetine; norepinephrine reuptake inhibitor) during extinction training would facilitate the extinction of drug-seeking behaviors, thus reducing relapse. Rats were trained that the presentation of a discrete cue signaled that a lever press response would result in cocaine reinforcement. Rats were subsequently extinguished and spontaneous recovery of drug-seeking behavior following presentation of previously drug-predictive cues was tested 4 weeks later. We find that compound stimulus presentations or pharmacologically increasing noradrenergic activity during extinction training results in less future recovery of responding, whereas propranolol treatment reduced the benefit seen with compound stimulus presentation. These data may have important implications for understanding the biological basis of extinction learning, as well as for improving the outcome of extinction-based therapies.
Stothers, R. B.
The possible influence of 'invisible matter' on the solar system's comet halo, and therefore on quasi-periodic cometary bombardment of the earth and consequent mass extinctions, is briefly addressed. Invisible matter consisting of small or cold interstellar molecular clouds could significantly modulate the comet background flux, while invisible matter consisting of a large population of old, dead stars with a relatively small galactic concentration probably could not. It is also shown that the downward force exerted by the Galaxy will perturb the halo, but will not produce any periodicity.
Lewis, David F V; Dorne, Jean-Lou C M
The linkage between astronomical cycles and the periodicity of mass extinctions is reviewed and discussed. In particular, the apparent 26 million year cycle of global extinctions may be related to the motion of the solar system around the galaxy, especially perpendicular to the galactic plane. The potential relevance of Milankovitch cycles is also explored in the light of current evidence for the possible causes of extinction events over a geological timescale.
Haselgrove, Mark; Pearce, John M
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.
Hunter, Amy Silvestri
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.
Morris, Richard W; Bouton, Mark E
Six experiments with rat subjects examined the effect of yohimbine, an alpha-2 adrenergic autoreceptor antagonist, on the extinction of conditioned fear to a tone. Experiments 1 and 2 demonstrated that systemic administration of yohimbine (1.0 mg/kg) facilitated a long-term decrease in freezing after extinction, and this depended on pairing drug administration with extinction training. However, Experiments 3 and 4 demonstrated that yohimbine did not eradicate the original fear learning: Freezing was renewed when the tone was tested outside of the extinction context. Experiments 5 and 6 found that the contextually specific attenuation of fear produced by yohimbine transferred to another extinguished conditional stimulus (CS) and not to a nonextinguished CS. The results suggest that yohimbine, when administered in the presence of a neutral context, creates a form of inhibition in that context that allows that specific context to reduce fear of an extinguished CS.
Bak, P.; Paczuski, M.
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.
Vurbic, Drina; Bouton, Mark E
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.
Oberlander, Sarah E; Shebl, Fatma M; Magder, Laurence S; Black, Maureen M
This study examined how the developmental processes of autonomy and relatedness are related to changes in the residential status of 181 first-time, adolescent, urban, low-income, African American mothers over the first 24 months postpartum. Although adolescent mothers were eager to live independently, few made a clear transition out of the multigenerational household; 56% lived in the household of origin continuously (IN), 21% left and never returned (OUT), and 23% had multiple moves in and out of the household (IN/OUT). Older adolescent maternal age, less supportive adolescent mother-grandmother relations, and high household density were associated with leaving the household of origin. The IN/OUT group had difficulty adopting the roles of adult and parent. Helping adolescent mothers and grandmothers negotiate roles to reduce conflict may promote autonomy and relatedness, allowing mothers to learn parenting skills, qualify for public assistance, and continue their education.
Yang, Yi-Ling; Su, Ya-Wen; Ng, Ming-Chong; Chao, Po-Kuan; Tung, Li-Chu; Lu, Kwok-Tung
A standard extract of Ginkgo biloba (EGb761) has been used in the treatment of various common geriatric complaints including vertigo, short-term memory loss, hearing loss, lack of attention, or vigilance. We demonstrated that acute systemic administration of EGb761 facilitated the acquisition of conditioned fear. Many studies suggest the neural mechanism underlies extinction is similar to the acquisition. This raises a possibility that EGb761 may modulate and accelerate the fear extinction process. We tested this possibility by using fear-potentiated startle (FPS) on laboratory rats. Acute systemic injection of EGb761 (10, 20, or 50 mg/kg) 30 min before extinction training facilitated extinction in a dose-dependent manner. Intra-amygdaloid infusion of EGb761 (28 ng/side, bilaterally) 10 min before extinction training also facilitated extinction. Control experiments showed that facilitation effect of EGb761 was not the result of impaired expression of conditioned fear or accelerated forgetting. Rats previously injected with EGb761 showed significant FPS after retraining. Extinction of conditioned fear appeared to result from acute drug effects rather than from toxic action. Systemic administration of EGb761 immediately after extinction training did not facilitate extinction, suggested the EGb761 facilitation effect is contributed to the acquisition phase of extinction learning. Western blot results showed that extinction induced amygdaloid extracellular signal-regulated kinase (ERK1/2) phosphorylation was significantly elevated by EGb761 treatment. Intra-amygdala injection of ERK1/2 inhibitor PD98059 completely blocked the EGb761 effect. Therefore, acute EGb761 administration modulated extinction of conditioned fear by activating ERK1/2.
Xin, Jian; Ma, Ling; Zhang, Tian-Yi; Yu, Hui; Wang, Yue; Kong, Liang; Chen, Zhe-Yu
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.
Been, Ella; Gómez-Olivencia, Asier; Kramer, Patricia A
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.
Ament, Marco; Zirr, Tobias; Dachsbacher, Carsten
We present a novel method to optimize the attenuation of light for the single scattering model in direct volume rendering. A common problem of single scattering is the high dynamic range between lit and shadowed regions due to the exponential attenuation of light along a ray. Moreover, light is often attenuated too strong between a sample point and the camera, hampering the visibility of important features. Our algorithm employs an importance function to selectively illuminate important structures and make them visible from the camera. With the importance function, more light can be transmitted to the features of interest, while contextual structures cast shadows which provide visual cues for perception of depth. At the same time, more scattered light is transmitted from the sample point to the camera to improve the primary visibility of important features. We formulate a minimization problem that automatically determines the extinction along a view or shadow ray to obtain a good balance between sufficient transmittance and attenuation. In contrast to previous approaches, we do not require a computationally expensive solution of a global optimization, but instead provide a closed-form solution for each sampled extinction value along a view or shadow ray and thus achieve interactive performance.
Krug, Andrew Z.; Patzkowsky, Mark E.
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
Krug, Andrew Z; Patzkowsky, Mark E
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.
...The U.S. Office of Personnel Management is issuing final regulations on the use of sick leave and advanced sick leave for serious communicable diseases, including pandemic influenza when appropriate. We are also permitting employees to substitute up to 26 weeks of accrued or accumulated sick leave for unpaid Family and Medical Leave Act (FMLA) leave to care for a seriously injured or ill......
Nelson, James Byron; Lamoureux, Jeffrey A
The Attentional Theory of Context Processing (ATCP) states that extinction will arouse attention to contexts resulting in learning becoming contextually controlled. Participants learned to suppress responding to colored sensors in a video-game task where contexts were provided by different gameplay backgrounds. Four experiments assessed the contextual control of simple excitatory learning acquired to a test stimulus (T) after (Exp. 1) or during (Exp. 2-4) extinction of another stimulus (X). Experiment 1 produced no evidence of contextual control of T, though renewal to X was present both at the time T was trained and tested. In Experiment 2 no contextual control of T was evident when X underwent extensive conditioning and extinction. In Experiment 3 no contextual control of T was evident after extensive conditioning and extinction of X, and renewal to X was present. In Experiment 4 contextual control was evident to T, but it neither depended upon nor was enhanced by extinction of X. The results presented here appear to limit the generality of ATCP.
Holmes, Nathan M; Griffiths, Oren; Westbrook, R Frederick
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.
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
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.
Urcelay, Gonzalo P.; Lipatova, Olga; Miller, Ralph R.
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…
Malkki, Hemi A I; Donga, Laura A B; de Groot, Sabine E; Battaglia, Francesco P; Pennartz, Cyriel M A
Extinction of instrumental responses is an essential skill for adaptive behavior such as foraging. So far, only few studies have focused on extinction following appetitive conditioning in mice. We studied extinction of appetitive operant lever-press behavior in six standard inbred mouse strains (A/J, C3H/HeJ, C57BL/6J, DBA/2J, BALB/cByJ and NOD/Ltj) and eight recombinant inbred mouse lines. From the response rates at the end of operant and extinction training we computed an extinction index, with higher values indicating better capability to omit behavioral responding in absence of reward. This index varied highly across the mouse lines tested, and the variability was partially due to a significant heritable component of 12.6%. To further characterize the relationship between operant learning and extinction, we calculated the slope of the time course of extinction across sessions. While many strains showed a considerable capacity to omit responding when lever pressing was no longer rewarded, we found a few lines showing an abnormally high perseveration in lever press behavior, showing no decay in response scores over extinction sessions. No correlation was found between operant and extinction response scores, suggesting that appetitive operant learning and extinction learning are dissociable, a finding in line with previous studies indicating that these forms of learning are dependent on different brain areas. These data shed light on the heritable basis of extinction learning and may help develop animal models of addictive habits and other perseverative disorders, such as compulsive food seeking and eating.
Lerman, Dorothea C.; Iwata, Brian A.
A commonly associated side effect of extinction as a treatment for behavior disorders is an initial increased frequency of the target response, called an "extinction burst." This study analyzed 113 sets of extinction data and found that extinction bursting occurred in only 24% of cases and was less common when extinction was combined…
Maurer, Verena; Murphy, Conor; Schmuckermair, Claudia; Muigg, Patrick; Neumann, Inga D.; Whittle, Nigel
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
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
Johnson, Justin S.; Escobar, Martha; Kimble, Whitney L.
Short acquisition-extinction intervals (immediate extinction) can lead to either more or less spontaneous recovery than long acquisition-extinction intervals (delayed extinction). Using rat subjects, we observed less spontaneous recovery following immediate than delayed extinction (Experiment 1). However, this was the case only if a relatively…
Leitenberg, H; Rawson, R A; Bath, K
Conditioned behavior declines in frequency when reinforcement is discontinued. In two experiments this extinction process was facilitated when competing behavior was reinforced as the original response was extinguished. When reinforcement for competing behavior was withdrawn, however, rats resumed their original behavior and there were no overall savings in total responses to extinction.
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 approximately 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.
Mitev, Valentin; Babichenko, S.; Borelli, R.; Fiorani, L.; Grigorov, I.; Nuvoli, M.; Palucci, A.; Pistilli, M.; Puiu, Ad.; Rebane, Ott; Santoro, S.
We present a lidar measurement of atmospheric extinction coefficient. The measurement is performed by inversion of the backscatter lidar signal at wavelengths 3'000nm and 3'500nm. The inversion of the backscatter lidar signal was performed with constant extinction-to-backscatter ration values of 104 and exponential factor 0.1.
Kinloch, Jennifer M.; Foster, T. Mary; McEwan, James S. A.
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);…
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.
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
Jazbi, B.; Hoyle, F.; Wickramasinghe, N. C.
The extinction efficiencies of randomly oriented infinite graphite cylinders, including hollow cylinders are calculated, using the rigorous Kerker-Matijevic formulas. The peak in the mid-UV extinction varies in wavelength with particle radius and cavity size in a way that makes such particles of limited interest as models of interstellar grains.
Harte, John; Ostling, Annette; Green, Jessica L; Kinzig, Ann
Thomas et al. have carried out a useful analysis of the extinction risk from climate warming. Their overall conclusion, that a large fraction of extant species could be driven to extinction by expected climate trends over the next 50 years, is compelling: it adds to the many other reasons why new energy policies are needed to reduce the pace of warming.
Sepkowski, J. John, Jr.
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.
Lundeberg, Thomas; Lund, Iréne
Both specific and non-specific factors, as well as the therapist, may play a role in acupuncture therapy. Recent results suggest that verum acupuncture has specific physiological effects and that patients expectations and belief regarding a potentially beneficial treatment modulate activity in the reward and self-appraisal systems in the brain. We suggest that acupuncture treatment may partly be regarded and used as an intervention that preconditions expectancy, which results in both conditional reflexes and conditioning of expected reward and self-appraisal. If so, acupuncture should preferably be applied before the start of the specific treatment (drug or behavioural intervention which is given with the intention of achieving a specific outcome) to enhance the specific and non-specific effects. This hypothesis is further supported by the suggestions that acupuncture may be viewed as a neural stimulus that triggers Pavlovian extinction. If this is the case, acupuncture should preferably be applied repeatedly (ie in a learning process) before the start of the specific treatment to initiate the extinction of previous unpleasant associations like pain or anxiety. Our clinical data suggest that acupuncture may precondition expectancy and conditional reflexes as well as induce Pavlovian extinction. Based on the above we suggest that acupuncture should be tried (as an adjunct) before any specific therapy.
Isabelle, Aaron D.; de Groot, Cornelis
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…
Poole, Millicent E.
Using a matched sample of students who stay in school and those who drop out, or leave early, an attempt was made, via multiple discriminant analysis, to identify the significant characteristics which distinguish "drop outs" from their peers who remain at school. Results indicated that both types of students have similar value orientations and…
Feng, Joyce Yen; Han, Wen-Jui
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…
Feng, Joyce Yen; Han, Wen-Jui
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
Hu, Airong; Lai, Miaojun; Wei, Jianzi; Wang, Lina; Mao, Huijuan; Zhou, Wenhua; Liu, Sheng
Augmentation of extinction with learning enhancing therapy may offer an effective strategy to combat heroin relapse. Our lab previously found that electroacupuncture (EA) not only significantly reduced cue-induced reinstatement of heroin seeking but also exhibited a promoting effect on the ability of learning and memory. In the present study, we further investigated the effects of EA on the extinction of heroin-seeking behavior in rats with a history of intravenous heroin self-administration. We trained Sprague-Dawley rats to nose-poke for i.v. heroin either daily for 4h or 25 infusions for 14 consecutive days; then the rats underwent 7 daily 3h extinction sessions in the operant chamber. To assess EA's effects on the extinction response of heroin-associated cues, 2Hz EA was administered 1h before each of the 7 extinction sessions. We also applied immunohistochemistry to detect FosB-positive nuclei in the nucleus accumbens core. We found that EA treatment facilitated the extinction response of heroin seeking but did not alter the locomotor activity in an open field testing environment. EA stimulation attenuated the FosB expression in the core of the nucleus accumbens, a brain region involved in the learning and execution of motor responses. Altogether, these results suggest that EA may provide a novel nonpharmacological approach to enhance extinction learning when combined with extinction therapy for the treatment of heroin addiction.
Crutzen, P J; Brühl, C
In a recent contribution to this journal Ellis and Schramm [Ellis, J. & Schramm, D. N. (1995) Proc. Natl. Acad. Sci. USA 92, 235-238] claim that supernova explosions can cause massive biological extinctions as a result of strongly enhanced stratospheric NOx (NO + NO2) production by accompanying galactic cosmic rays. They suggested that these NOx productions which would last over several centuries and occur once every few hundred million years would result in ozone depletions of about 95%, leading to vastly increased levels of biologically damaging solar ultraviolet radiation. Our detailed model calculations show, however, substantially smaller ozone depletions ranging from at most 60% at high latitudes to below 20% at the equator. PMID:11607631
Régnier, Claire; Achaz, Guillaume; Lambert, Amaury; Cowie, Robert H.; Bouchet, Philippe; Fontaine, Benoît
Since the 1980s, many have suggested we are in the midst of a massive extinction crisis, yet only 799 (0.04%) of the 1.9 million known recent species are recorded as extinct, questioning the reality of the crisis. This low figure is due to the fact that the status of very few invertebrates, which represent the bulk of biodiversity, have been evaluated. Here we show, based on extrapolation from a random sample of land snail species via two independent approaches, that we may already have lost 7% (130,000 extinctions) of the species on Earth. However, this loss is masked by the emphasis on terrestrial vertebrates, the target of most conservation actions. Projections of species extinction rates are controversial because invertebrates are essentially excluded from these scenarios. Invertebrates can and must be assessed if we are to obtain a more realistic picture of the sixth extinction crisis. PMID:26056308
Faith, J Tyler; Surovell, Todd A
The late Pleistocene witnessed the extinction of 35 genera of North American mammals. The last appearance dates of 16 of these genera securely fall between 12,000 and 10,000 radiocarbon years ago (approximately 13,800-11,400 calendar years B.P.), although whether the absence of fossil occurrences for the remaining 19 genera from this time interval is the result of sampling error or temporally staggered extinctions is unclear. Analysis of the chronology of extinctions suggests that sampling error can explain the absence of terminal Pleistocene last appearance dates for the remaining 19 genera. The extinction chronology of North American Pleistocene mammals therefore can be characterized as a synchronous event that took place 12,000-10,000 radiocarbon years B.P. Results favor an extinction mechanism that is capable of wiping out up to 35 genera across a continent in a geologic instant.
Rossato, Janine I.; Bevilaqua, Lia R.; Izquierdo, Iván; Medina, Jorge H.; Cammarota, Martín
The nonreinforced expression of long-tem memory may lead to two opposite protein synthesis-dependent processes: extinction and reconsolidation. Extinction weakens consolidated memories, whereas reconsolidation allows incorporation of additional information into them. Knowledge about these two processes has accumulated in recent years, but their possible interaction has not been evaluated yet. Here, we report that inhibition of protein synthesis in the CA1 region of the dorsal hippocampus after retrieval of fear extinction impedes subsequent reactivation of the extinction memory trace without affecting its storage or that of the initial fear memory. Our results suggest that extinction memory is susceptible to a retrieval-induced process similar to reconsolidation in the hippocampus. PMID:21118982
Rossato, Janine I; Bevilaqua, Lia R; Izquierdo, Iván; Medina, Jorge H; Cammarota, Martín
The nonreinforced expression of long-tem memory may lead to two opposite protein synthesis-dependent processes: extinction and reconsolidation. Extinction weakens consolidated memories, whereas reconsolidation allows incorporation of additional information into them. Knowledge about these two processes has accumulated in recent years, but their possible interaction has not been evaluated yet. Here, we report that inhibition of protein synthesis in the CA1 region of the dorsal hippocampus after retrieval of fear extinction impedes subsequent reactivation of the extinction memory trace without affecting its storage or that of the initial fear memory. Our results suggest that extinction memory is susceptible to a retrieval-induced process similar to reconsolidation in the hippocampus.
Régnier, Claire; Achaz, Guillaume; Lambert, Amaury; Cowie, Robert H; Bouchet, Philippe; Fontaine, Benoît
Since the 1980s, many have suggested we are in the midst of a massive extinction crisis, yet only 799 (0.04%) of the 1.9 million known recent species are recorded as extinct, questioning the reality of the crisis. This low figure is due to the fact that the status of very few invertebrates, which represent the bulk of biodiversity, have been evaluated. Here we show, based on extrapolation from a random sample of land snail species via two independent approaches, that we may already have lost 7% (130,000 extinctions) of the species on Earth. However, this loss is masked by the emphasis on terrestrial vertebrates, the target of most conservation actions. Projections of species extinction rates are controversial because invertebrates are essentially excluded from these scenarios. Invertebrates can and must be assessed if we are to obtain a more realistic picture of the sixth extinction crisis.
Tonn, Bruce Edward
This paper presents a framework to judge whether we are meeting our ethical responsibilities for preventing massive species extinction. The framework is a generalization from another framework, one that addresses ethical responsibilities related to preventing premature, involuntary human deaths from environmental risks and the extinction of the human race. The resulting ethical risk standards are quite stringent and it is argued that we are nowhere close to meeting any standards, except in the cases of human extinction and extinction of all life on earth, which are met by chance, not by design. Much work is needed to build the 'technology' needed to estimate probabilities associated with massive losses of human life and species extinction over the suggested 1000 year planning horizon.
Faith, J. Tyler; Surovell, Todd A.
The late Pleistocene witnessed the extinction of 35 genera of North American mammals. The last appearance dates of 16 of these genera securely fall between 12,000 and 10,000 radiocarbon years ago (≈13,800–11,400 calendar years B.P.), although whether the absence of fossil occurrences for the remaining 19 genera from this time interval is the result of sampling error or temporally staggered extinctions is unclear. Analysis of the chronology of extinctions suggests that sampling error can explain the absence of terminal Pleistocene last appearance dates for the remaining 19 genera. The extinction chronology of North American Pleistocene mammals therefore can be characterized as a synchronous event that took place 12,000–10,000 radiocarbon years B.P. Results favor an extinction mechanism that is capable of wiping out up to 35 genera across a continent in a geologic instant. PMID:19934040
Valentino, Amber L; Shillingsburg, M Alice; Call, Nathan A; Burton, Britney; Bowen, Crystal N
Children with autism have significant communication delays. Although some children develop vocalizations through shaping and differential reinforcement, others rarely exhibit vocalizations, and alternative methods are targeted in intervention. However, vocal language often remains a goal for caregivers and clinicians. Thus, strategies to increase frequency of vocalizations are needed. In the present study, the authors examined the effect of extinction of previously acquired signed mands on vocalizations in three children diagnosed with autism. Experiment 1 examined the effects of differential reinforcement of vocalizations and extinction of signed mands combined. In Experiment 1, it was unknown whether the reinforcement of vocalizations alone could have produced the effects; therefore, Experiment 2 isolated the effects of reinforcement and extinction by reinforcing vocalizations in baseline. An increase in rate of vocalizations occurred following the application of extinction of signed mands and differential reinforcement of vocalizations in Experiment 1 and following extinction of signed mands in Experiment 2.
Huston, J P; van den Brink, J; Komorowski, M; Huq, Y; Topic, B
The withholding of expected rewards results in extinction of behavior and, hypothetically, to depression-like symptoms. In a test of this hypothesis, we examined the effects of extinction of food-reinforced lever-pressing on collateral behaviors that might be indices of depression. Operant extinction is known to be aversive to the organism and results in avoidance behavior. We hypothesized that avoidance of, or withdrawal from, the former source of reward may serve as a marker for "despair." Adult male Wistar rats (n=6-7 animals per group) were exposed to a Skinner box attached to a second compartment of the same size, providing opportunity for the animals to leave the operant chamber and to enter the "withdrawal" compartment. The animals spent a portion of the time during the extinction trials in this second chamber. To assess the predictive validity of this behavior as a potential marker of "despair," we tested the effects of chronic administration of two common antidepressant drugs on this measure. The tricyclic antidepressant imipramine (20 mg/kg) as well as the selective serotonin reuptake inhibitor citalopram (20 mg/kg) reduced the number of entries and time spent in the withdrawal compartment. We propose that entries into and time spent in the withdrawal compartment may operationalize "avoidance," a core symptom of major depression. Rearing as well as biting behaviors during the extinction trials were also attenuated by the antidepressant treatment. These results lend support to the hypothesis that extinction of positively reinforced operants evokes behaviors that reflect elements of "despair/depression" because these behaviors are modulated by antidepressant treatment. The avoidance of the operant chamber as a consequence of extinction, together with rearing and biting behaviors, may serve as useful measures for the testing of antidepressant treatments.
Prost, S; Knapp, M; Flemmig, J; Hufthammer, A K; Kosintsev, P; Stiller, M; Hofreiter, M
The Pleistocene to Holocene transition was accompanied by a worldwide extinction event affecting numerous mammalian species. Several species such as the woolly mammoth and the giant deer survived this extinction wave, only to go extinct a few thousand years later during the Holocene. Another example for such a Holocene extinction is the Don-hare, Lepus tanaiticus, which inhabited the Russian plains during the late glacial. After being slowly replaced by the extant mountain hare (Lepus timidus), it eventually went extinct during the middle Holocene. Here, we report the phylogenetic relationship of L. tanaiticus and L. timidus based on a 339-basepair (bp) fragment of the mitochondrial D-loop. Phylogenetic tree- and network reconstructions do not support L. tanaiticus and L. timidus being different species. Rather, we suggest that the two taxa represent different morphotypes of a single species and the extinction of 'L. tanaiticus' represents the disappearance of a local morphotype rather than the extinction of a species.
Kitzes, Justin; Harte, John
A significant challenge in both measuring and predicting species extinction rates at global and local scales is the possibility of extinction debt, time-delayed extinctions that occur gradually following an initial impact. Here we examine how relative abundance distributions and spatial aggregation combine to influence the likely magnitude of future extinction debt following habitat loss or climate-driven range contraction. Our analysis is based on several fundamental premises regarding abundance distributions, most importantly that species abundances immediately following habitat loss are a sample from an initial relative abundance distribution and that the long-term, steady-state form of the species abundance distribution is a property of the biology of a community and not of area. Under these two hypotheses, the results show that communities following canonical lognormal and broken-stick abundance distributions are prone to exhibit extinction debt, especially when species exhibit low spatial aggregation. Conversely, communities following a logseries distribution with a constant Fisher's α parameter never demonstrate extinction debt and often show an "immigration credit," in which species richness rises in the long term following an initial decrease. An illustration of these findings in 25 biodiversity hotspots suggests a negligible immediate extinction rate for bird communities and eventual extinction debts of 30-50% of initial species richness, whereas plant communities are predicted to immediately lose 5-15% of species without subsequent extinction debt. These results shed light on the basic determinants of extinction debt and provide initial indications of the magnitude of likely debts in landscapes where few empirical data are available.
Davidson, Ana D; Boyer, Alison G; Kim, Hwahwan; Pompa-Mansilla, Sandra; Hamilton, Marcus J; Costa, Daniel P; Ceballos, Gerardo; Brown, James H
The world's oceans are undergoing profound changes as a result of human activities. However, the consequences of escalating human impacts on marine mammal biodiversity remain poorly understood. The International Union for the Conservation of Nature (IUCN) identifies 25% of marine mammals as at risk of extinction, but the conservation status of nearly 40% of marine mammals remains unknown due to insufficient data. Predictive models of extinction risk are crucial to informing present and future conservation needs, yet such models have not been developed for marine mammals. In this paper, we: (i) used powerful machine-learning and spatial-modeling approaches to understand the intrinsic and extrinsic drivers of marine mammal extinction risk; (ii) used this information to predict risk across all marine mammals, including IUCN "Data Deficient" species; and (iii) conducted a spatially explicit assessment of these results to understand how risk is distributed across the world's oceans. Rate of offspring production was the most important predictor of risk. Additional predictors included taxonomic group, small geographic range area, and small social group size. Although the interaction of both intrinsic and extrinsic variables was important in predicting risk, overall, intrinsic traits were more important than extrinsic variables. In addition to the 32 species already on the IUCN Red List, our model identified 15 more species, suggesting that 37% of all marine mammals are at risk of extinction. Most at-risk species occur in coastal areas and in productive regions of the high seas. We identify 13 global hotspots of risk and show how they overlap with human impacts and Marine Protected Areas.
Kutlu, Munir Gunes; Holliday, Erica; Gould, Thomas J
Previously, studies from our lab have shown that while acute nicotine administered prior to training and testing enhances contextual fear conditioning, acute nicotine injections prior to extinction sessions impair extinction of contextual fear. Although there is also strong evidence showing that the acute nicotine's enhancing effects on contextual fear conditioning require high-affinity α4β2 nicotinic acetylcholine receptors (nAChRs), it is unknown which nAChR subtypes are involved in the acute nicotine-induced impairment of contextual fear extinction. In this study, we investigated the effects of acute nicotine administration on contextual fear extinction in knock-out (KO) mice lacking α4, β2 or α7 subtypes of nAChRs and their wild-type (WT) littermates. Both KO and WT mice were first trained and tested for contextual fear conditioning and received a daily contextual extinction session for 4 days. Subjects received intraperitoneal injections of nicotine (0.18 mg/kg) or saline 2-4 min prior to each extinction session. Our results showed that the mice that lack α4 and β2 subtypes of nAChRs showed normal contextual fear extinction but not the acute nicotine-induced impairment while the mice that lack the α7 subtype showed both normal contextual extinction and nicotine-induced impairment of contextual extinction. In addition, control experiments showed that acute nicotine-induced impairment of contextual fear extinction persisted when nicotine administration was ceased and repeated acute nicotine administrations alone did not induce freezing behavior in the absence of context-shock learning. These results clearly demonstrate that high-affinity α4β2 nAChRs are necessary for the effects of acute nicotine on contextual fear extinction.
Bredy, Timothy W.; Barad, Mark
Histone modifications contribute to the epigenetic regulation of gene expression, a process now recognized to be important for the consolidation of long-term memory. Valproic acid (VPA), used for many years as an anticonvulsant and a mood stabilizer, has effects on learning and memory and enhances the extinction of conditioned fear through its…
Pedreira, Maria Eugenia; Perez-Cuesta, Luis Maria; Maldonado, Hector
In previous experiments on contextual memory, we proposed that the unreinforced re-exposure to the learning context (conditioned stimulus, CS) acts as a switch guiding the memory course toward reconsolidation or extinction, depending on reminder duration. This proposal implies that the system computes the total exposure time to the context, from…
Barker, Jacqueline M.; Taylor, Jane R.; Chandler, L. Judson
The infralimbic prefrontal cortex (IL) has been shown to be critical for the regulation of flexible behavior, but its precise function remains unclear. This region has been shown to be critical for the acquisition, consolidation, and expression of extinction learning, leading many to hypothesize that IL suppresses behavior as part of a…
Childs, Jessica E.; DeLeon, Jaime; Nickel, Emily; Kroener, Sven
Drugs of abuse cause changes in the prefrontal cortex (PFC) and associated regions that impair inhibitory control over drug-seeking. Breaking the contingencies between drug-associated cues and the delivery of the reward during extinction learning reduces rates of relapse. Here we used vagus nerve stimulation (VNS) to induce targeted synaptic…
Akirav, Irit; Segev, Amir; Motanis, Helen; Maroun, Mouna
We investigated whether the N-methyl-D-aspartate (NMDA) receptor partial agonist D-cycloserine (DCS, 20 microg/side) microinfused into the basolateral amygdala (BLA) would reverse stress-induced impairment of extinction in two aversive learning paradigms: contextual fear conditioning and conditioned taste aversion (CTA). We found that DCS in the BLA show differential involvement in the extinction of these two paradigms and in its modulation of stress-induced impairment of extinction. This may suggest that the dysfunctional extinction of fear and taste aversion following exposure to a stressful experience may be modulated by different mechanisms.
Sturm, Anna; Czisch, Michael; Spoormaker, Victor I
Impaired fear extinction and disturbed sleep coincide in post-traumatic stress disorder (PTSD), but the nature of this relationship is unclear. Rapid eye movement (REM) sleep deprivation impairs fear extinction recall in rodents and young healthy subjects, and animal models have demonstrated both disrupted sleep after fear conditioning and normalized sleep after extinction learning. As a correlation between unconditioned stimulus (US) responding and subsequent sleep architecture has been observed in healthy subjects, the goal of this study was to test whether US intensity would causally affect subsequent sleep. Twenty-four young healthy subjects underwent a fear conditioning session with skin conductance response measurements before an afternoon session of polysomnographically recorded sleep (up to 120 min) in the sleep laboratory. Two factors were manipulated experimentally in a 2 × 2 design: US (electrical shock) was set at high or low intensity, and subjects did or did not receive an extinction session after fear conditioning. We observed that neither factor affected REM sleep amount, that high US intensity nominally increased sleep fragmentation (more Stage 1 sleep, stage shifts and wake after sleep onset), and that extinction increased Stage 4 amount. Moreover, reduced Stage 1 and increased Stage 4 and REM sleep were associated with subjective sleep quality of the afternoon nap. These results provide evidence for the notion that US intensity and extinction affect subsequent sleep architecture in young healthy subjects, which may provide a translational bridge from findings in animal studies to correlations observed in PTSD patients.
Den, Miriam Liora; Graham, Bronwyn M; Newall, Carol; Richardson, Rick
This study investigated differences between adolescents and adults on fear conditioning, extinction, and reinstatement (i.e., the recovery of conditioned fear following re-exposure to the unconditioned stimulus [US] post-extinction). Participants underwent differential conditioning (i.e., the Screaming Lady) where one neutral face (CS+) was followed by the same face expressing fear and a loud scream (US) while another neutral face (CS-) remained neutral. Extinction involved non-reinforced presentations of both CSs, after which participants were reinstated (2xUSs) or not. On two self-report measures, both ages showed conditioning, good extinction learning and retention, and reinstatement-induced relapse. However, only adolescents showed conditioning, extinction, and reinstatement on the eye tracking measure; relapse on this measure could not be assessed in adults given they did not show initial conditioning. Lastly, higher levels of depression predicted stronger conditioning and weaker extinction in adolescents only. These findings are discussed in terms of their implications for adolescent anxiety disorders.
Guedea, Anita L; Schrick, Christina; Guzman, Yomayra F; Leaderbrand, Katie; Jovasevic, Vladimir; Corcoran, Kevin A; Tronson, Natalie C; Radulovic, Jelena
Extensive research has unraveled the molecular basis of learning processes underlying contextual fear conditioning, but the mechanisms of fear extinction remain less known. Contextual fear extinction occurs when an aversive stimulus that initially caused fear is no longer present and depends on the activation of the extracellular signal-regulated kinase (ERK), among other molecules. Here we investigated how ERK signaling triggered by extinction affects its downstream targets belonging to the activator protein-1 (AP-1) transcription factor family. We found that extinction, when compared to conditioning of fear, markedly enhanced the interactions of active, phospho-ERK (pERK ) with c-Jun causing alterations of its phosphorylation state. The AP-1 binding of c-Jun was decreased whereas AP-1 binding of JunD, Jun dimerization protein 2 (JDP2) and ERK were significantly enhanced. The increased AP-1 binding of the inhibitory JunD and JDP2 transcription factors was paralleled by decreased levels of the AP-1 regulated proteins c-Fos and GluR2. These changes were specific for extinction and were MEK-dependent. Overall, fear extinction involves ERK/Jun interactions and a decrease of a subset of AP-1-regulated proteins that are typically required for fear conditioning. Facilitating the formation of inhibitory AP-1 complexes may thus facilitate the reduction of fear.
Godsil, B P; Bontempi, B; Mailliet, F; Delagrange, P; Spedding, M; Jay, T M
Antidepressant drugs are commonly prescribed treatments for anxiety disorders, and there is growing interest in understanding how these drugs impact fear extinction because extinction learning is pivotal to successful exposure-based therapy (EBT). A key objective within this domain is understanding how antidepressants alter the activation of specific elements of the limbic-based network that governs such fear processing. Chronic treatment with the antidepressant tianeptine has been shown to reduce the acquisition of extinction learning in rats, yet the drug's acute influence on activation in prefrontal and amygdalar regions, and on extinction learning are not well understood. To assess its influence on cellular activation, rats were injected with tianeptine and Fos immunoreactivity was measured in these regions. Acute tianeptine treatment selectively altered Fos expression within subdivisions of the central nucleus of the amygdala (CEA) in a bidirectional manner that varied in relation to ongoing activation within the capsular subdivision and its prefrontal and intra-amygdalar inputs. This pattern of results suggests that the drug can conditionally modulate the activation of CEA subdivisions, which contain microcircuits strongly implicated in fear processing. The effect of acute tianeptine was also examined with respect to the acquisition, consolidation and expression of fear extinction in rats. Acute tianeptine attenuated extinction learning as well as the recall of extinction memory, which underscores that acute dosing with the drug could alter learning during EBT. Together these findings provide a new perspective for understanding the mechanism supporting tianeptine's clinical efficacy, as well as its potential influence on CEA-based learning mechanisms.
Cannady, Reginald; McGonigal, Justin T; Newsom, Ryan J; Woodward, John J; Mulholland, Patrick J; Gass, Justin T
Identifying novel treatments that facilitate extinction learning could enhance cue-exposure therapy and reduce high relapse rates in alcoholics. Activation of mGlu5 receptors in the infralimbic prefrontal cortex (IL-PFC) facilitates learning during extinction of cue-conditioned alcohol-seeking behavior. Small-conductance calcium-activated potassium (KCa2) channels have also been implicated in extinction learning of fear memories, and mGlu5 receptor activation can reduce KCa2 channel function. Using a combination of electrophysiological, pharmacological, and behavioral approaches, this study examined KCa2 channels as a novel target to facilitate extinction of alcohol-seeking behavior in rats. This study also explored related neuronal and synaptic mechanisms within the IL-PFC that underlie mGlu5-dependent enhancement of extinction learning. Using whole-cell patch clamp electrophysiology, activation of mGlu5 in ex vivo slices significantly reduced KCa2 channel currents in layer V IL-PFC pyramidal neurons, confirming functional down-regulation of KCa2 channel activity by mGlu5 receptors. Additionally, positive modulation of KCa2 channels prevented mGlu5 receptor-dependent facilitation of long-term potentiation in the IL-PFC. Systemic and intra-IL-PFC treatment with apamin (KCa2 channel allosteric inhibitor) significantly enhanced extinction of alcohol-seeking behavior across multiple extinction sessions; an effect that persisted for 3 weeks, but was not observed after apamin treatment in the prelimbic PFC. Positive modulation of IL-PFC KCa2 channels significantly attenuated mGlu5-dependent facilitation of alcohol cue-conditioned extinction learning. These data suggest that mGlu5-dependent facilitation of extinction learning and synaptic plasticity in the IL-PFC involves functional inhibition of KCa2 channels. Moreover, these findings demonstrate that KCa2 channels are a novel target to facilitate long-lasting extinction of alcohol-seeking behavior
Differential involvement of medial prefrontal cortex and basolateral amygdala extracellular signal-regulated kinase in extinction of conditioned taste aversion is dependent on different intervals of extinction following conditioning.
Lin, P-Y; Wang, S-P; Tai, M-Y; Tsai, Y-F
Extinction reflects a decrease in the conditioned response (CR) following non-reinforcement of a conditioned stimulus. Behavioral evidence indicates that extinction involves an inhibitory learning mechanism in which the extinguished CR reappears with presentation of an unconditioned stimulus. However, recent studies on fear conditioning suggest that extinction erases the original conditioning if the time interval between fear acquisition and extinction is short. The present study examined the effects of different intervals between acquisition and extinction of the original memory in conditioned taste aversion (CTA). Male Long-Evans rats acquired CTA by associating a 0.2% sucrose solution with malaise induced by i.p. injection of 4 ml/kg 0.15 M LiCl. Two different time intervals, 5 and 24 h, between CTA acquisition and extinction were used. Five or 24 h after CTA acquisition, extinction trials were performed, in which a bottle containing 20 ml of a 0.2% sucrose solution was provided for 10 min without subsequent LiCl injection. If sucrose consumption during the extinction trials was greater than the average water consumption, then rats were considered to have reached CTA extinction. Rats subjected to extinction trials lasting 24 h, but not 5 h, after acquisition re-exhibited the extinguished CR following injection of 0.15 M LiCl alone 7 days after acquisition. Extracellular signal-regulated kinase (ERK) in the medial prefrontal cortex (mPFC) and basolateral nucleus of the amygdala (BLA) was examined by Western blot after the first extinction trial. ERK activation in the mPFC was induced after the extinction trial beginning 5 h after acquisition, whereas the extinction trial performed 24 h after acquisition induced ERK activation in the BLA. These data suggest that the original conditioning can be inhibited or retained by CTA extinction depending on the time interval between acquisition and extinction and that the ERK transduction pathway in the mPFC and BLA is
Rappaport, Sarah J; Riddoch, M Jane; Chechlacz, Magda; Humphreys, Glyn W
There is good evidence that early visual processing involves the coding of different features in independent brain regions. A major question, then, is how we see the world in an integrated manner, in which the different features are "bound" together. A standard account of this has been that feature binding depends on attention to the stimulus, which enables only the relevant features to be linked together [Treisman, A., & Gelade, G. A feature-integration theory of attention. Cognitive Psychology, 12, 97-136, 1980]. Here we test this influential idea by examining whether, in patients showing visual extinction, the processing of otherwise unconscious (extinguished) stimuli is modulated by presenting objects in their correct (familiar) color. Correctly colored objects showed reduced extinction when they had a learned color, and this color matched across the ipsi- and contralesional items (red strawberry + red tomato). In contrast, there was no reduction in extinction under the same conditions when the stimuli were colored incorrectly (blue strawberry + blue tomato; Experiment 1). The result was not due to the speeded identification of a correctly colored ipsilesional item, as there was no benefit from having correctly colored objects in different colors (red strawberry + yellow lemon; Experiment 2). There was also no benefit to extinction from presenting the correct colors in the background of each item (Experiment 3). The data suggest that learned color-form binding can reduce extinction even when color is irrelevant for the task. The result is consistent with preattentive binding of color and shape for familiar stimuli.
Baratta, Michael V.; Pomrenze, Matthew B.; Nakamura, Shinya; Dolzani, Samuel D.; Cooper, Donald C.
Extinction is a form of inhibitory learning viewed as an essential process in suppressing conditioned responses to drug cues, yet there is little information concerning experiential variables that modulate its formation. Coping factors play an instrumental role in determining how adverse life events impact the transition from casual drug use to addiction. Here we provide evidence in rat that prior exposure to controllable stress accelerates the extinction of cocaine-seeking behavior relative to uncontrollable or no stress exposure. Subsequent experimentation using high-speed optogenetic tools determined if the infralimbic region (IL) of the ventral medial prefrontal cortex mediates the impact of controllable stress on cocaine-seeking behavior. Photoinhibition of pyramidal neurons in the IL during coping behavior did not interfere with subject's ability to control the stressor, but prevented the later control-induced facilitation of extinction. These results provide strong evidence that the degree of behavioral control over adverse events, rather than adverse events per se, potently modulates the extinction of cocaine-seeking behavior, and that controllable stress engages prefrontal circuitry that primes future extinction learning. PMID:25954765
Baratta, Michael V; Pomrenze, Matthew B; Nakamura, Shinya; Dolzani, Samuel D; Cooper, Donald C
Extinction is a form of inhibitory learning viewed as an essential process in suppressing conditioned responses to drug cues, yet there is little information concerning experiential variables that modulate its formation. Coping factors play an instrumental role in determining how adverse life events impact the transition from casual drug use to addiction. Here we provide evidence in rat that prior exposure to controllable stress accelerates the extinction of cocaine-seeking behavior relative to uncontrollable or no stress exposure. Subsequent experimentation using high-speed optogenetic tools determined if the infralimbic region (IL) of the ventral medial prefrontal cortex mediates the impact of controllable stress on cocaine-seeking behavior. Photoinhibition of pyramidal neurons in the IL during coping behavior did not interfere with subject's ability to control the stressor, but prevented the later control-induced facilitation of extinction. These results provide strong evidence that the degree of behavioral control over adverse events, rather than adverse events per se, potently modulates the extinction of cocaine-seeking behavior, and that controllable stress engages prefrontal circuitry that primes future extinction learning.
Perry, Christina J; Reed, Felicia; Zbukvic, Isabel C; Kim, Jee Hyun
Background and Purpose There is currently no medication approved specifically to treat cocaine addiction. Behavioural interventions such as cue exposure therapy (CET) rely heavily on new learning. Antagonism of the metabotropic glutamate 5 (mGlu5) receptor has emerged as a potential treatment, by reducing the reinforcing properties of cocaine. However, mGlu5 receptor activity is necessary for learning; therefore, such agents could interfere with behavioural treatments. We used a novel rodent model of CET to test the effects of mGlu5 negative and positive allosteric modulators (NAM and PAM) on behavioural therapy. Experimental Approach Rats were trained to press a lever for cocaine in the presence of a discrete cue [conditioned stimulus (CS)] and then extinguished in the absence of the CS. Following lever extinction, half the rats received CS extinction in the same chambers but with the levers withdrawn; the remaining rats received no CS extinction. Before this session, rats received a systemic administration of either vehicle or a mGlu5 NAM (MTEP, experiment 1) or PAM (CDPPB, experiment 2). Cue‐induced reinstatement was tested in a drug‐free session the following day. Key Results At reinstatement, rats that had received CS extinction showed reduced responding. This effect was attenuated by MTEP treatment before CS extinction. In contrast, administration of CDPPB (PAM) led to decreased reinstatement the following day, regardless of extinction condition. Conclusion and Implications These results suggest that mGlu5 receptor activity is both necessary and sufficient for efficient extinction of a cocaine‐associated CS. Therefore, mGlu5 PAMs could enhance the efficacy of CET. PMID:26784278
Baum, William M
The traditional molecular view of behavior explains extinction as the dissipation or inhibition of strength, formerly built up by contiguous reinforcement. In obstinate opposition to this explanation was the partial-reinforcement extinction effect: a partially reinforced response extinguishes more slowly than a continuously reinforced response. It suggests instead that extinction is discrimination. Four pigeons were exposed to daily sessions in which a variable period of food delivery, produced by pecking on a variable-interval schedule, was followed by extinction. The rate of food delivery was varied over a wide range across conditions. Varying the amount of food per delivery inversely with rate of delivery kept response rate from varying excessively. The results confirmed and extended the partial-reinforcement effect; persistence of pecking and time to extinction were inversely related to rate of obtaining food. The results support the molar view of extinction, not as loss of strength of a particular discrete response, but as a transition from one allocation of time among activities to another. Although molecular theories dismiss discrimination due to repeated training and extinction as an impurity or complication, repeated cycles of availability and privation are probably typical of the environment in which most vertebrate species evolved.
Jernvall, J; Wright, P C
Many extant species are at risk to go extinct. This impending loss of species is likely to cause changes in future ecosystem functions. Ecological components of diversity, such as dietary or habitat specializations, can be used to estimate the impact of extinctions on ecosystem functions. As an approach to estimate the impact of future extinctions, we tested interdependency between ecological and taxonomic change based on current predictions of extinction rates in primates. We analyzed the ecological characteristics of extant primate faunas having species in various categories of endangerment of extinction and forecasted the future primate faunas as if they were paleontological faunas. Predicting future faunas combines the wealth of ecological information on living primates with large, fossil record-like changes in diversity. Predicted extinction patterns of living primates in Africa, Asia, Madagascar, and South America show that changes in ecology differ among the regions in ways that are not reducible to taxonomic measures. The ecological effects of primate extinctions are initially least severe in South America and larger in Asia and Africa. Disproportionately larger ecological changes are projected for Madagascar. The use of taxonomy as a proxy for ecology can mislead when estimating competence of future primate ecosystems.
Nevin, John A
In the metaphor of behavioral momentum, reinforcement is assumed to strengthen discriminated operant behavior in the sense of increasing its resistance to disruption, and extinction is viewed as disruption by contingency termination and reinforcer omission. In multiple schedules of intermittent reinforcement, resistance to extinction is an increasing function of reinforcer rate, consistent with a model based on the momentum metaphor. The partial-reinforcement extinction effect, which opposes the effects of reinforcer rate, can be explained by the large disruptive effect of terminating continuous reinforcement despite its strengthening effect during training. Inclusion of a term for the context of reinforcement during training allows the model to account for a wide range of multiple-schedule extinction data and makes contact with other formulations. The relation between resistance to extinction and reinforcer rate on single schedules of intermittent reinforcement is exactly opposite to that for multiple schedules over the same range of reinforcer rates; however, the momentum model can give an account of resistance to extinction in single as well as multiple schedules. An alternative analysis based on the number of reinforcers omitted to an extinction criterion supports the conclusion that response strength is an increasing function of reinforcer rate during training.
Pappens, Meike; Schroijen, Mathias; Van den Bergh, Omer; Van Diest, Ilse
Fear reduction obtained during a fear extinction procedure can generalize from the extinction stimulus to other perceptually similar stimuli. Perceptual generalization of fear extinction typically follows a perceptual gradient, with increasing levels of fear reduction the more a stimulus resembles the extinction stimulus. The current study aimed to investigate whether perceptual generalization of fear extinction can be observed also after a retention interval of 24h. Fear was acquired to three geometrical figures of different sizes (CS(+), CS1(+) and CS2(+)) by consistently pairing them with a short-lasting suffocation experience (US). Three other geometrical figures that were never followed by the US served as control stimuli (CS(-), CS1(-), CS2(-)). Next, only the CS(+) was extinguished by presenting it in the absence of the US. One day later, fear responses to all stimuli were assessed without any US-presentation. Outcome measures included startle blink EMG, skin conductance, US expectancy, respiratory rate and tidal volume. On day 2 spontaneous recovery of fear was observed in US expectancy and tidal volume, but not in the other outcomes. Evidence for the retention of fear extinction generalization was present in US expectancy and skin conductance, but a perceptual gradient in the retention of generalized fear extinction could not be observed.
Grady, Ashley K; Bowen, Kenton H; Hyde, Andrew T; Totsch, Stacie K; Knight, David C
Extinction of Pavlovian conditioned fear in humans is a popular paradigm often used to study learning and memory processes that mediate anxiety-related disorders. Fear extinction studies often only pair the conditioned stimulus (CS) and unconditioned stimulus (UCS) on a subset of acquisition trials (i.e., partial reinforcement/pairing) to prolong extinction (i.e., partial reinforcement extinction effect; PREE) and provide more time to study the process. However, there is limited evidence that the partial pairing procedures typically used during fear conditioning actually extend the extinction process, while there is strong evidence these procedures weaken conditioned response (CR) acquisition. Therefore, determining conditioning procedures that support strong CR acquisition and that also prolong the extinction process would benefit the field. The present study investigated 4 separate CS-UCS pairing procedures to determine methods that support strong conditioning and that also exhibit a PREE. One group (C-C) of participants received continuous CS-UCS pairings; a second group (C-P) received continuous followed by partial CS-UCS pairings; a third group (P-C) received partial followed by continuous CS-UCS pairings; and a fourth group (P-P) received partial CS-UCS pairings during acquisition. A strong skin conductance CR was expressed by C-C and P-C groups but not by C-P and P-P groups at the end of the acquisition phase. The P-C group maintained the CR during extinction. In contrast, the CR extinguished quickly within the C-C group. These findings suggest that partial followed by continuous CS-UCS pairings elicit strong CRs and prolong the extinction process following human fear conditioning.
Payne, Jonathan L; Finnegan, Seth
Wide geographic range is generally thought to buffer taxa against extinction, but the strength of this effect has not been investigated for the great majority of the fossil record. Although the majority of genus extinctions have occurred between major mass extinctions, little is known about extinction selectivity regimes during these "background" intervals. Consequently, the question of whether selectivity regimes differ between background and mass extinctions is largely unresolved. Using logistic regression, we evaluated the selectivity of genus survivorship with respect to geographic range by using a global database of fossil benthic marine invertebrates spanning the Cambrian through the Neogene periods, an interval of approximately 500 My. Our results show that wide geographic range has been significantly and positively associated with survivorship for the great majority of Phanerozoic time. Moreover, the significant association between geographic range and survivorship remains after controlling for differences in species richness and abundance among genera. However, mass extinctions and several second-order extinction events exhibit less geographic range selectivity than predicted by range alone. Widespread environmental disturbance can explain the reduced association between geographic range and extinction risk by simultaneously affecting genera with similar ecological and physiological characteristics on global scales. Although factors other than geographic range have certainly affected extinction risk during many intervals, geographic range is likely the most consistently significant predictor of extinction risk in the marine fossil record.
Bieszczad, Kasia M; Weinberger, Norman M
Primary sensory cortices are traditionally regarded as stimulus analysers. However, studies of associative learning-induced plasticity in the primary auditory cortex (A1) indicate involvement in learning, memory and other cognitive processes. For example, the area of representation of a tone becomes larger for stronger auditory memories and the magnitude of area gain is proportional to the degree that a tone becomes behaviorally important. Here, we used extinction to investigate whether 'behavioral importance' specifically reflects a sound's ability to predict reinforcement (reward or punishment) vs. to predict any significant change in the meaning of a sound. If the former, then extinction should reverse area gains as the signal no longer predicts reinforcement. Rats (n = 11) were trained to bar-press to a signal tone (5.0 kHz) for water-rewards, to induce signal-specific area gains in A1. After subsequent withdrawal of reward, A1 was mapped to determine representational areas. Signal-specific area gains, estimated from a previously established brain-behavior quantitative function, were reversed, supporting the 'reinforcement prediction' hypothesis. Area loss was specific to the signal tone vs. test tones, further indicating that withdrawal of reinforcement, rather than unreinforced tone presentation per se, was responsible for area loss. Importantly, the amount of area loss was correlated with the amount of extinction (r = 0.82, P < 0.01). These findings show that primary sensory cortical representation can encode behavioral importance as a signal's value to predict reinforcement, and that the number of cells tuned to a stimulus can dictate its ability to command behavior.
Bieszczad, Kasia M.; Weinberger, Norman M.
Primary sensory cortices are traditionally regarded as stimulus analyzers. However, studies of associative learning-induced plasticity in the primary auditory cortex (A1) indicate involvement in learning, memory and other cognitive processes. For example, the area of representation of a tone becomes larger for stronger auditory memories and the magnitude of area gain is proportional to the degree that a tone becomes behaviorally important. Here, we used extinction to investigate whether “behavioral importance” specifically reflects a sound’s ability to predict reinforcement (reward or punishment) vs. to predict any significant change in the meaning of a sound. If the former, then extinction should reverse area gains as the signal no longer predicts reinforcement. Rats (n = 11) were trained to bar-press to a signal tone (5.0 kHz) for water-rewards, to induce signal-specific area gains in A1. After subsequent withdrawal of reward, A1 was mapped to determine representational areas. Signal-specific area gains — estimated from a previously established brain–behavior quantitative function — were reversed, supporting the “reinforcement prediction” hypothesis. Area loss was specific to the signal tone vs. test tones, further indicating that withdrawal of reinforcement, rather than unreinforced tone presentation per se, was responsible for area loss. Importantly, the amount of area loss was correlated with the amount of extinction (r = 0.82, p < 0.01). These findings show that primary sensory cortical representation can encode behavioral importance as a signal’s value to predict reinforcement, and that the number of cells tuned to a stimulus can dictate its ability to command behavior. PMID:22304434
Reynolds, G. S.
The resistance of responding to extinction after variable-interval reinforcement in one of two components of a multiple schedule of reinforcement was (1) greater, when responding in the second component was rein