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Sample records for classical fear conditioning

  1. Effects of local anesthesia of the cerebellum on classical fear conditioning in goldfish

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    Hirano Ruriko

    2010-03-01

    Full Text Available Abstract Background Besides the amygdala, of which emotion roles have been intensively studied, the cerebellum has also been demonstrated to play a critical role in simple classical fear conditioning in both mammals and fishes. In the present study, we examined the effect of local administration of the anesthetic agent lidocaine into the cerebellum on fear-related, classical heart-rate conditioning in goldfish. Methods The effects of microinjection of the anesthetic agent lidocaine into the cerebellum on fear conditioning were investigated in goldfish. The fear conditioning paradigm was delayed classical conditioning with light as a conditioned stimulus and electric shock as an unconditioned stimulus; cardiac deceleration (bradycardia was the conditioned response. Results Injecting lidocaine into the cerebellum had no effect on the base heart rate, an arousal/orienting response to the novel stimulus (i.e., the first presentation of light, or an unconditioned response to electric shock. However, lidocaine injection greatly impaired acquisition of conditioned bradycardia. Lidocaine injection 60 min before the start of the conditioning procedure showed no effect on acquisition of conditioned bradycardia, indicating that the effect of lidocaine was reversible. Conclusions The present results further confirm the idea that the cerebellum in teleost fish, as in mammals, is critically involved in classical fear conditioning.

  2. Conditioned withdrawal in goldfish: a simple and inexpensive preparation for the study of classical fear conditioning in vertebrates.

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    Barela, Peter B

    2012-02-01

    Summary.-A preparation for the study of classical fear conditioning in vertebrates is described. Its unique features are that it is inexpensive and easy to construct and operate. The following classical conditioning phenomena are demonstrated using this preparation: excitatory conditioning, extinction, contextual conditioning, blocking, a conditioned inhibition discrimination, and latent inhibition.

  3. Differential Transcriptional Response to Nonassociative and Associative Components of Classical Fear Conditioning in the Amygdala and Hippocampus

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    Isiegas, Carolina; Stein, Joel; Hellman, Kevin; Hannenhalli, Sridhar; Abel, Ted; Keeley, Michael B.; Wood, Marcelo A.

    2006-01-01

    Classical fear conditioning requires the recognition of conditioned stimuli (CS) and the association of the CS with an aversive stimulus. We used Affymetrix oligonucleotide microarrays to characterize changes in gene expression compared to naive mice in both the amygdala and the hippocampus 30 min after classical fear conditioning and 30 min after…

  4. Updated meta-analysis of classical fear conditioning in the anxiety disorders.

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    Duits, Puck; Cath, Danielle C; Lissek, Shmuel; Hox, Joop J; Hamm, Alfons O; Engelhard, Iris M; van den Hout, Marcel A; Baas, Joke M P

    2015-04-01

    The aim of the current study was twofold: (1) to systematically examine differences in fear conditioning between anxiety patients and healthy controls using meta-analytic methods, and (2) to examine the extent to which study characteristics may account for the variability in findings across studies. Forty-four studies (published between 1920 and 2013) with data on 963 anxiety disordered patients and 1,222 control subjects were obtained through PubMed and PsycINFO, as well as from a previous meta-analysis on fear conditioning (Lissek et al.). Results demonstrated robustly increased fear responses to conditioned safety cues (CS-) in anxiety patients compared to controls during acquisition. This effect may represent an impaired ability to inhibit fear in the presence of safety cues (CS-) and/or may signify an increased tendency in anxiety disordered patients to generalize fear responses to safe stimuli resembling the conditioned danger cue (CS+). In contrast, during extinction, patients show stronger fear responses to the CS+ and a trend toward increased discrimination learning (differentiation between the CS+ and CS-) compared to controls, indicating delayed and/or reduced extinction of fear in anxiety patients. Finally, none of the included study characteristics, such as the type of fear measure (subjective vs. psychophysiological index of fear), could account significantly for the variance in effect sizes across studies. Further research is needed to investigate the predictive value of fear extinction on treatment outcome, as extinction processes are thought to underlie the beneficial effects of exposure treatment in anxiety disorders.

  5. Emotional stress evoked by classical fear conditioning induces yawning behavior in rats.

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    Kubota, Natsuko; Amemiya, Seiichiro; Yanagita, Shinya; Nishijima, Takeshi; Kita, Ichiro

    2014-04-30

    Yawning is often observed not only in a state of boredom or drowsiness but also in stressful emotional situations, suggesting that yawning is an emotional behavior. However, the neural mechanisms for yawning during stressful emotional situations have not been fully determined, though previous studies have suggested that both parvocellular oxytocin (OT) and corticotropin-releasing factor (CRF) neurons in the hypothalamic paraventricular nucleus (PVN) are responsible for induction of yawning. Thus, using ethological observations and c-Fos immunohistochemistry, we examined whether emotional stress evoked by classical fear conditioning is involved in induction of yawning behavior in freely moving rats. Emotional stress induced yawning behavior that was accompanied by anxiety-related behavior, and caused neuronal activation of the central nucleus of the amygdala (CeA), as well as increases in activity of both OT and CRF neurons in the PVN. These results suggest that emotional stress may induce yawning behavior, in which the neuronal activation of the CeA may have a key role.

  6. Serotonin in fear conditioning processes.

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    Bauer, Elizabeth P

    2015-01-15

    This review describes the latest developments in our understanding of how the serotonergic system modulates Pavlovian fear conditioning, fear expression and fear extinction. These different phases of classical fear conditioning involve coordinated interactions between the extended amygdala, hippocampus and prefrontal cortices. Here, I first define the different stages of learning involved in cued and context fear conditioning and describe the neural circuits underlying these processes. The serotonergic system can be manipulated by administering serotonin receptor agonists and antagonists, as well as selective serotonin reuptake inhibitors (SSRIs), and these can have significant effects on emotional learning and memory. Moreover, variations in serotonergic genes can influence fear conditioning and extinction processes, and can underlie differential responses to pharmacological manipulations. This research has considerable translational significance as imbalances in the serotonergic system have been linked to anxiety and depression, while abnormalities in the mechanisms of conditioned fear contribute to anxiety disorders.

  7. Classical conditioning of autonomic fear responses is independent of contingency awareness.

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    Schultz, Douglas H; Helmstetter, Fred J

    2010-10-01

    The role of contingency awareness in classical conditioning experiments using human subjects is currently under debate. This study took a novel approach to manipulating contingency awareness in a differential Pavlovian conditioning paradigm. Complex sine wave gratings were used as visual conditional stimuli (CS). By manipulating the fundamental spatial frequency of the displays, we were able to construct pairs of stimuli that varied in discriminability. One group of subjects was given an "easy" discrimination, and another was exposed to a "difficult" CS+ and CS-. A 3rd group was exposed to a stimulus that was paired with the unconditional stimulus (UCS) 50% of the time and served as a control. Skin conductance response (SCR) and continuous UCS expectancy data were measured concurrently throughout the experiment. Differential UCS expectancy was found only in the easy discrimination group. Differential SCRs were found in the easy discrimination group as well as in the difficult discrimination group, but not in the 50% contingency control. The difficult discrimination group did not exhibit differential UCS expectancy but did show clear differential SCR. These observations support a dual process interpretation of classical conditioning whereby conditioning on an implicit level can occur without explicit knowledge about the contingencies. The role of contingency awareness in classical conditioning experiments using human subjects is currently under debate. This study took a novel approach to manipulating contingency awareness in a differential Pavlovian conditioning paradigm. Complex sine wave gratings were used as visual conditional stimuli (CS). By manipulating the fundamental spatial frequency of the displays, we were able to construct pairs of stimuli that varied in discriminability. One group of subjects was given an "easy" discrimination, and another was exposed to a "difficult" CS+ and CS-. A 3rd group was exposed to a stimulus that was paired with the

  8. The involvement of ventral tegmental area cholinergic muscarinic receptors in classically conditioned fear expression as measured with fear-potentiated startle.

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    Greba, Q; Munro, L J; Kokkinidis, L

    2000-07-01

    Accumulating evidence suggests that dopamine (DA) neurons in the ventral tegmental area (VTA) contribute to the complex amygdala-based neurocircuitry that mediates fear-motivated behaviors. Because of acetylcholine's (ACh) role in DA neuronal activation, the involvement of VTA cholinergic muscarinic receptors in Pavlovian conditioned fear responding was evaluated in the present study. Fear-potentiated startle was used to assess the effects of intraVTA infused methylscopolamine on conditioned fear performance in laboratory rats. Application of this nonspecific muscarinic receptor antagonist to VTA neurons was observed to inhibit the ability of a conditioned stimulus (CS) previously paired with footshock to enhance the amplitude of the acoustic startle reflex. Doses of methylscopolamine that blocked conditioned fear expression did not alter baseline sensorimotor responding. These results identify ACh neurotransmission in the VTA as a potential excitatory mechanism underlying the fear-arousing properties of threatening environmental stimuli.

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

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

    2016-04-01

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

  10. Serotonergic Modulation of Conditioned Fear

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    Judith R. Homberg

    2012-01-01

    Full Text Available Conditioned fear plays a key role in anxiety disorders as well as depression and other neuropsychiatric conditions. Understanding how neuromodulators drive the associated learning and memory processes, including memory consolidation, retrieval/expression, and extinction (recall, is essential in the understanding of (individual differences in vulnerability to these disorders and their treatment. The human and rodent studies I review here together reveal, amongst others, that acute selective serotonin reuptake inhibitor (SSRI treatment facilitates fear conditioning, reduces contextual fear, and increases cued fear, chronic SSRI treatment reduces both contextual and cued fear, 5-HT1A receptors inhibit the acquisition and expression of contextual fear, 5-HT2A receptors facilitates the consolidation of cued and contextual fear, inactivation of 5-HT2C receptors facilitate the retrieval of cued fear memory, the 5-HT3 receptor mediates contextual fear, genetically induced increases in serotonin levels are associated with increased fear conditioning, impaired cued fear extinction, or impaired extinction recall, and that genetically induced 5-HT depletion increases fear conditioning and contextual fear. Several explanations are presented to reconcile seemingly paradoxical relationships between serotonin levels and conditioned fear.

  11. Brief fear preexposure facilitates subsequent fear conditioning.

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    Iwasaki, Satoshi; Sakaguchi, Tetsuya; Ikegaya, Yuji

    2015-06-01

    Post-traumatic stress disorder (PTSD) is an anxiety disorder that occurs following an unexpected exposure to a severe psychological event. A history of a brief trauma is reported to affect a risk for future PTSD development; however, little is known about the mechanisms by which a previous trauma exposure drives the sensitivity to a late-coming trauma. Using a mouse PTSD model, we found that a prior foot shock enhances contextual fear conditioning. This shock-induced facilitation of fear conditioning (i.e., priming effect) persisted for 7 days and was prevented by MK801, an N-methyl-D-aspartate receptor antagonist. Other types of trauma, such as forced swimming or tail pinch, did not induce a priming effect on fear conditioning. Thus, a trauma is unlikely generalized to modify the sensitivity to other traumatic experiences. The behavioral procedure employed in this study may be a useful tool to elucidate the etiology of PTSD.

  12. N-methyl-D-aspartate receptor antagonist MK-801 impairs learning but not memory fixation or expression of classical fear conditioning in goldfish (Carassius auratus).

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    Xu, X; Davis, R E

    1992-04-01

    The amnestic effects of the noncompetitive antagonist MK-801 on visually mediated, classic fear conditioning in goldfish (Carassius auratus) was examined in 5 experiments. MK-801 was administered 30 min before the training session on Day 1 to look for anterograde amnestic effects, immediately after training to look for retrograde amnestic effects, and before the training or test session, or both, to look for state-dependence effects. The results showed that MK-801 produced anterograde amnesia at doses that did not produce retrograde amnesia or state dependency and did not impair the expression of conditioned or unconditioned branchial suppression responses (BSRs) to the conditioned stimulus. The results indicate that MK-801 disrupts the mechanism of learning of the conditioned stimulus-unconditioned stimulus relation. Evidence is also presented that the learning processes that are disrupted by MK-801 occur during the initial stage of BSR conditioning.

  13. Posterior insular cortex is necessary for conditioned inhibition of fear.

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    Foilb, Allison R; Flyer-Adams, Johanna G; Maier, Steven F; Christianson, John P

    2016-10-01

    Veridical detection of safety versus danger is critical to survival. Learned signals for safety inhibit fear, and so when presented, reduce fear responses produced by danger signals. This phenomenon is termed conditioned inhibition of fear. Here, we report that CS+/CS- fear discrimination conditioning over 5 days in rats leads the CS- to become a conditioned inhibitor of fear, as measured by the classic tests of conditioned inhibition: summation and retardation of subsequent fear acquisition. We then show that NMDA-receptor antagonist AP5 injected to posterior insular cortex (IC) before training completely prevented the acquisition of a conditioned fear inhibitor, while intra-AP5 to anterior and medial IC had no effect. To determine if the IC contributes to the recall of learned fear inhibition, injections of the GABAA agonist muscimol were made to posterior IC before a summation test. This resulted in fear inhibition per se, which obscured inference to the effect of IC inactivation with recall of the safety cue. Control experiments sought to determine if the role of the IC in conditioned inhibition learning could be reduced to simpler fear discrimination function, but fear discrimination and recall were unaffected by AP5 or muscimol, respectively, in the posterior IC. These data implicate a role of posterior IC in the learning of conditioned fear inhibitors.

  14. Worrying affects associative fear learning: a startle fear conditioning study.

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    Femke J Gazendam

    Full Text Available A valuable experimental model for the pathogenesis of anxiety disorders is that they originate from a learned association between an intrinsically non-aversive event (Conditioned Stimulus, CS and an anticipated disaster (Unconditioned Stimulus, UCS. Most anxiety disorders, however, do not evolve from a traumatic experience. Insights from neuroscience show that memory can be modified post-learning, which may elucidate how pathological fear can develop after relatively mild aversive events. Worrying--a process frequently observed in anxiety disorders--is a potential candidate to strengthen the formation of fear memory after learning. Here we tested in a discriminative fear conditioning procedure whether worry strengthens associative fear memory. Participants were randomly assigned to either a Worry (n = 23 or Control condition (n = 25. After fear acquisition, the participants in the Worry condition processed six worrisome questions regarding the personal aversive consequences of an electric stimulus (UCS, whereas the Control condition received difficult but neutral questions. Subsequently, extinction, reinstatement and re-extinction of fear were tested. Conditioned responding was measured by fear-potentiated startle (FPS, skin conductance (SCR and UCS expectancy ratings. Our main results demonstrate that worrying resulted in increased fear responses (FPS to both the feared stimulus (CS(+ and the originally safe stimulus (CS(-, whereas FPS remained unchanged in the Control condition. In addition, worrying impaired both extinction and re-extinction learning of UCS expectancy. The implication of our findings is that they show how worry may contribute to the development of anxiety disorders by affecting associative fear learning.

  15. Dopaminergic Activity in the Medial Prefrontal Cortex Modulates Fear Conditioning

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    Parvin Babaei

    2011-07-01

    Full Text Available "nThe purpose of the present study was to determine the role of medial prefrontal cortex (mPFC dopaminergic system in fear conditioning response considering individual differences. Animals were initially counterbalanced and classified based on open field test, and then were given a single infusion of the dopamine agonist, amphetamine (AMPH and antagonist, clozapine (CLZ into the medial prefrontal cortex. Rats received tone-shock pairing in a classical fear conditioning test and then exposed to the tone alone. Freezing responses were measured as conditioned fear index. The results showed that both AMPH and CLZ infusion in mPFC reduced the expression of conditioned fear. This finding indicates that elevation or reduction in the dopaminergic activity is associated with the decrease of fear responses, despite preexisting individual-typological differences.

  16. Odors eliciting fear: a conditioning approach to Idiopathic Environmental Intolerances.

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    Leer, Arne; Smeets, Monique A M; Bulsing, Patricia J; van den Hout, Marcel A

    2011-06-01

    Patients suffering from Idiopathic Environmental Intolerances (IEI) report health symptoms, referable to multiple organ systems, which are triggered by harmless odors and therefore medically unexplainable. In line with previous research that predominantly points towards psychological explanations, the present study tests the hypothesis that IEI symptoms result from learning via classical conditioning of odors to fear. A differential conditioning paradigm was employed. Hedonically different odors were compared on ease of fear acquisition. Conditioned stimuli (CSs) were Dimethyl Sulfide (unpleasant) and peach (pleasant). The unconditioned stimulus (US) was an electrical shock. During acquisition one odor (CS+) was followed by shock, while the other odor (CS-) was not. Next, fear extinction was tested by presenting both CS+ and CS- without US. Electrodermal response, odor evaluation, and sniffing behavior were monitored. Results showed successful fear conditioning irrespective of hedonic character as evidenced by electrodermal response. Acquired fear did not extinguish. There was no evidence of evaluative conditioning taking place, as CS evaluation did not change during fear acquisition. Early avoidance of the CS+, as deduced from odor inhalation measures, was demonstrated, but did not sustain during the entire acquisition phase. This study suggests that a fear conditioning account of IEI is only partially satisfactory.

  17. Pain pathways involved in fear conditioning measured with fear-potentiated startle: lesion studies.

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    Shi, C; Davis, M

    1999-01-01

    It is well established that the basolateral amygdala is critically involved in the association between an unconditioned stimulus (US), such as a foot shock, and a conditioned stimulus (CS), such as a light, during classic fear conditioning. However, little is known about how the US (pain) inputs are relayed to the basolateral amygdala. The present studies were designed to define potential US pathways to the amygdala using lesion methods. Electrolytic lesions before or after training were placed in caudal granular/dysgranular insular cortex (IC) alone or in conjunction with the posterior intralaminar nuclei of the thalamus (PoT/PIL), and the effects on fear conditioning were examined. Pretraining lesions of both IC and PoT/PIL, but not lesions of IC alone, blocked the acquisition of fear-potentiated startle. However, post-training combined lesions of IC and PoT/PIL did not prevent expression of conditioned fear. Given that previous studies have shown that lesions of PoT/PIL alone had no effect on acquisition of conditioned fear, these results suggest that two parallel cortical (insula-amygdala) and subcortical (PoT/PIL-amygdala) pathways are involved in relaying shock information to the basolateral amygdala during fear conditioning.

  18. Fear conditioning is disrupted by damage to the postsubiculum.

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    Robinson, Siobhan; Bucci, David J

    2012-06-01

    The hippocampus plays a central role in spatial and contextual learning and memory, however relatively little is known about the specific contributions of parahippocampal structures that interface with the hippocampus. The postsubiculum (PoSub) is reciprocally connected with a number of hippocampal, parahippocampal and subcortical structures that are involved in spatial learning and memory. In addition, behavioral data suggest that PoSub is needed for optimal performance during tests of spatial memory. Together, these data suggest that PoSub plays a prominent role in spatial navigation. Currently it is unknown whether the PoSub is needed for other forms of learning and memory that also require the formation of associations among multiple environmental stimuli. To address this gap in the literature we investigated the role of PoSub in Pavlovian fear conditioning. In Experiment 1 male rats received either lesions of PoSub or Sham surgery prior to training in a classical fear conditioning procedure. On the training day a tone was paired with foot shock three times. Conditioned fear to the training context was evaluated 24 hr later by placing rats back into theconditioning chamber without presenting any tones or shocks. Auditory fear was assessed on the third day by presenting the auditory stimulus in a novel environment (no shock). PoSub-lesioned rats exhibited impaired acquisition of the conditioned fear response as well as impaired expression of contextual and auditory fear conditioning. In Experiment 2, PoSub lesions were made 1 day after training to specifically assess the role of PoSub in fear memory. No deficits in the expression of contextual fear were observed, but freezing to the tone was significantly reduced in PoSub-lesioned rats compared to shams. Together, these results indicate that PoSub is necessary for normal acquisition of conditioned fear, and that PoSub contributes to the expression of auditory but not contextual fear memory.

  19. Teaching and Demonstrating Classical Conditioning.

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    Sparrow, John; Fernald, Peter

    1989-01-01

    Discusses classroom demonstrations of classical conditioning and notes tendencies to misrepresent Pavlov's procedures. Describes the design and construction of the conditioner that is used for demonstrating classical conditioning. Relates how students experience conditioning, generalization, extinction, discrimination, and spontaneous recovery.…

  20. A Complete Reanalysis of Horner's Classic "Fear of Success" Study.

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    Brandt, David A.; Kline, Kay H.

    The well-known study on fear of success (FOS) by Horner (1968) asserted that women low in FOS do better on achievement-oriented tasks under competitive conditions, while women high in the motive do better when the situation is non-competitive. This paper critically reviews the methodology of this study and concludes that the statistical test…

  1. Can prepared fear conditioning result from verbal instructions?

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    Mertens, Gaëtan; Raes, An K.; De Houwer, Jan

    2016-01-01

    Evolutionary fear-relevant stimuli such as snakes or spiders are thought to be prepared to elicit fear reactions. This implies that the acquisition of conditioned fear responses is facilitated when these stimuli serve as conditioned stimuli (CSs). Moreover, extinction of conditioned fear responses i

  2. Contextual and auditory fear conditioning continue to emerge during the periweaning period in rats.

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    Burman, Michael A; Erickson, Kristen J; Deal, Alex L; Jacobson, Rose E

    2014-01-01

    Anxiety disorders often emerge during childhood. Rodent models using classical fear conditioning have shown that different types of fear depend upon different neural structures and may emerge at different stages of development. For example, some work has suggested that contextual fear conditioning generally emerges later in development (postnatal day 23-24) than explicitly cued fear conditioning (postnatal day 15-17) in rats. This has been attributed to an inability of younger subjects to form a representation of the context due to an immature hippocampus. However, evidence that contextual fear can be observed in postnatal day 17 subjects and that cued fear conditioning continues to emerge past this age raises questions about the nature of this deficit. The current studies examine this question using both the context pre-exposure facilitation effect for immediate single-shock contextual fear conditioning and traditional cued fear conditioning using Sprague-Dawley rats. The data suggest that both cued and contextual fear conditioning are continuing to develop between PD 17 and 24, consistent with development occurring the in essential fear conditioning circuit.

  3. Contextual and auditory fear conditioning continue to emerge during the periweaning period in rats.

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    Michael A Burman

    Full Text Available Anxiety disorders often emerge during childhood. Rodent models using classical fear conditioning have shown that different types of fear depend upon different neural structures and may emerge at different stages of development. For example, some work has suggested that contextual fear conditioning generally emerges later in development (postnatal day 23-24 than explicitly cued fear conditioning (postnatal day 15-17 in rats. This has been attributed to an inability of younger subjects to form a representation of the context due to an immature hippocampus. However, evidence that contextual fear can be observed in postnatal day 17 subjects and that cued fear conditioning continues to emerge past this age raises questions about the nature of this deficit. The current studies examine this question using both the context pre-exposure facilitation effect for immediate single-shock contextual fear conditioning and traditional cued fear conditioning using Sprague-Dawley rats. The data suggest that both cued and contextual fear conditioning are continuing to develop between PD 17 and 24, consistent with development occurring the in essential fear conditioning circuit.

  4. Conditioned Fear Acquisition and Generalization in Generalized Anxiety Disorder.

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    Tinoco-González, Daniella; Fullana, Miquel Angel; Torrents-Rodas, David; Bonillo, Albert; Vervliet, Bram; Blasco, María Jesús; Farré, Magí; Torrubia, Rafael

    2015-09-01

    Abnormal fear conditioning processes (including fear acquisition and conditioned fear-generalization) have been implicated in the pathogenesis of anxiety disorders. Previous research has shown that individuals with panic disorder present enhanced conditioned fear-generalization in comparison to healthy controls. Enhanced conditioned fear-generalization could also characterize generalized anxiety disorder (GAD), but research so far is inconclusive. An important confounding factor in previous research is comorbidity. The present study examined conditioned fear-acquisition and fear-generalization in 28 patients with GAD and 30 healthy controls using a recently developed fear acquisition and generalization paradigm assessing fear-potentiated startle and online expectancies of the unconditioned stimulus. Analyses focused on GAD patients without comorbidity but included also patients with comorbid anxiety disorders. Patients and controls did not differ as regards fear acquisition. However, contrary to our hypothesis, both groups did not differ either in most indexes of conditioned fear-generalization. Moreover, dimensional measures of GAD symptoms were not correlated with conditioned fear-generalization indexes. Comorbidity did not have a significant impact on the results. Our data suggest that conditioned fear-generalization is not enhanced in GAD. Results are discussed with special attention to the possible effects of comorbidity on fear learning abnormalities.

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

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    Dalla, Christina; Shors, Tracey J

    2009-05-25

    Males and females learn and remember differently at different times in their lives. These differences occur in most species, from invertebrates to humans. We review here sex differences as they occur in laboratory rodent species. We focus on classical and operant conditioning paradigms, including classical eyeblink conditioning, fear-conditioning, active avoidance and conditioned taste aversion. Sex differences have been reported during acquisition, retention and extinction in most of these paradigms. In general, females perform better than males in the classical eyeblink conditioning, in fear-potentiated startle and in most operant conditioning tasks, such as the active avoidance test. However, in the classical fear-conditioning paradigm, in certain lever-pressing paradigms and in the conditioned taste aversion, males outperform females or are more resistant to extinction. Most sex differences in conditioning are dependent on organizational effects of gonadal hormones during early development of the brain, in addition to modulation by activational effects during puberty and adulthood. Critically, sex differences in performance account for some of the reported effects on learning and these are discussed throughout the review. Because so many mental disorders are more prevalent in one sex than the other, it is important to consider sex differences in learning when applying animal models of learning for these disorders. Finally, we discuss how sex differences in learning continue to alter the brain throughout the lifespan. Thus, sex differences in learning are not only mediated by sex differences in the brain, but also contribute to them.

  6. Differential roles of the dorsal and ventral hippocampus in predator odor contextual fear conditioning.

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    Wang, Melissa E; Fraize, Nicolas P; Yin, Linda; Yuan, Robin K; Petsagourakis, Despina; Wann, Ellen G; Muzzio, Isabel A

    2013-06-01

    The study of fear memory is important for understanding various anxiety disorders in which patients experience persistent recollections of traumatic events. These memories often involve associations of contextual cues with aversive events; consequently, Pavlovian classical conditioning is commonly used to study contextual fear learning. The use of predator odor as a fearful stimulus in contextual fear conditioning has become increasingly important as an animal model of anxiety disorders. Innate fear responses to predator odors are well characterized and reliable; however, attempts to use these odors as unconditioned stimuli in fear conditioning paradigms have proven inconsistent. Here we characterize a contextual fear conditioning paradigm using coyote urine as the unconditioned stimulus. We found that contextual conditioning induced by exposure to coyote urine produces long-term freezing, a stereotypic response to fear observed in mice. This paradigm is context-specific and parallels shock-induced contextual conditioning in that it is responsive to extinction training and manipulations of predator odor intensity. Region-specific lesions of the dorsal and ventral hippocampus indicate that both areas are independently required for the long-term expression of learned fear. These results in conjunction with c-fos immunostaining data suggest that while both the dorsal and ventral hippocampus are required for forming a contextual representation, the ventral region also modulates defensive behaviors associated with predators. This study provides information about the individual contributions of the dorsal and ventral hippocampus to ethologically relevant fear learning.

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

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    Kida, Satoshi

    2014-11-01

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

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

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

    2016-05-01

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

  9. Fear conditioning with film clips: a complex associative learning paradigm

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    A.E. Kunze; A. Arntz; M. Kindt

    2014-01-01

    Background and objectives: We argue that the stimuli used in traditional fear conditioning paradigms are too simple to model the learning and unlearning of complex fear memories. We therefore developed and tested an adapted fear conditioning paradigm, specifically designed for the study of complex a

  10. Fear conditioning with film clips: a complex associative learning paradigm

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    Kunze, A.E.; Arntz, A.; Kindt, M.

    2015-01-01

    Background and objectives: We argue that the stimuli used in traditional fear conditioning paradigms are too simple to model the learning and unlearning of complex fear memories. We therefore developed and tested an adapted fear conditioning paradigm, specifically designed for the study of complex a

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

    Directory of Open Access Journals (Sweden)

    Michael Lukas Meier

    2014-07-01

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

  12. The conditions that promote fear learning: prediction error and Pavlovian fear conditioning.

    Science.gov (United States)

    Li, Susan Shi Yuan; McNally, Gavan P

    2014-02-01

    A key insight of associative learning theory is that learning depends on the actions of prediction error: a discrepancy between the actual and expected outcomes of a conditioning trial. When positive, such error causes increments in associative strength and, when negative, such error causes decrements in associative strength. Prediction error can act directly on fear learning by determining the effectiveness of the aversive unconditioned stimulus or indirectly by determining the effectiveness, or associability, of the conditioned stimulus. Evidence from a variety of experimental preparations in human and non-human animals suggest that discrete neural circuits code for these actions of prediction error during fear learning. Here we review the circuits and brain regions contributing to the neural coding of prediction error during fear learning and highlight areas of research (safety learning, extinction, and reconsolidation) that may profit from this approach to understanding learning.

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

    OpenAIRE

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

    2015-01-01

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

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

    OpenAIRE

    2014-01-01

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

  15. Neural circuitry underlying the regulation of conditioned fear and its relation to extinction.

    Science.gov (United States)

    Delgado, Mauricio R; Nearing, Katherine I; Ledoux, Joseph E; Phelps, Elizabeth A

    2008-09-11

    Recent efforts to translate basic research to the treatment of clinical disorders have led to a growing interest in exploring mechanisms for diminishing fear. This research has emphasized two approaches: extinction of conditioned fear, examined across species; and cognitive emotion regulation, unique to humans. Here, we sought to examine the similarities and differences in the neural mechanisms underlying these two paradigms for diminishing fear. Using an emotion regulation strategy, we examine the neural mechanisms of regulating conditioned fear using fMRI and compare the resulting activation pattern with that observed during classic extinction. Our results suggest that the lateral PFC regions engaged by cognitive emotion regulation strategies may influence the amygdala, diminishing fear through similar vmPFC connections that are thought to inhibit the amygdala during extinction. These findings further suggest that humans may have developed complex cognition that can aid in regulating emotional responses while utilizing phylogenetically shared mechanisms of extinction.

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

    Science.gov (United States)

    Torrents-Rodas, David; Fullana, Miquel A; Bonillo, Albert; Caseras, Xavier; Andión, Oscar; Torrubia, Rafael

    2013-02-01

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

  17. Versatility of Fear-potentiated Startle Paradigms for Assessing Human Conditioned Fear Extinction and Return of Fear

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    Seth Davin Norrholm

    2011-11-01

    Full Text Available Fear conditioning methodologies have often been employed as testable models for assessing learned fear responses in individuals with anxiety disorders such as post-traumatic stress disorder (PTSD and specific phobia. One frequently used paradigm is measurement of the acoustic startle reflex under conditions that mimic anxiogenic and fear-related conditions. For example, fear-potentiated startle is the relative increase in the frequency or magnitude of the acoustic startle reflex in the presence of a previously neutral cue (e.g., colored shape; termed the conditioned stimulus or CS+ that has been repeatedly paired with an aversive unconditioned stimulus (e.g., airblast to the larynx. Our group has recently used fear-potentiated startle paradigms to demonstrate impaired fear extinction in civilian and combat populations with PTSD. In the current study, we examined the use of either visual or auditory CSs in a fear extinction protocol that we have validated and applied to human clinical conditions. This represents an important translational bridge in that numerous animal studies of fear extinction, upon which much of the human work is based, have employed the use of auditory CSs as opposed to visual CSs. Participants in both the visual and auditory groups displayed robust fear-potentiated startle to the CS+, clear discrimination between the reinforced CS+ and non-reinforced CS-, significant extinction to the previously reinforced CS+, and marked spontaneous recovery. We discuss the current results as they relate to future investigations of PTSD-related impairments in fear processing in populations with diverse medical and psychiatric histories.

  18. Fear less : Individual differences in fear conditioning and their relation to treatment outcome in anxiety disorders

    NARCIS (Netherlands)

    Duits, P.

    2016-01-01

    Findings from animal and human experimental studies highlight the importance of fear conditioning processes in the development and treatment of anxiety disorders. The work reported in this thesis was focused on potential abnormalities in the acquisition and extinction of fear in patients with anxiet

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

    OpenAIRE

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Nicholas L Balderston

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

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

    Science.gov (United States)

    Balderston, Nicholas L; Schultz, Douglas H; Baillet, Sylvain; Helmstetter, Fred J

    2014-01-01

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

  2. Cotinine enhances the extinction of contextual fear memory and reduces anxiety after fear conditioning.

    Science.gov (United States)

    Zeitlin, Ross; Patel, Sagar; Solomon, Rosalynn; Tran, John; Weeber, Edwin J; Echeverria, Valentina

    2012-03-17

    Posttraumatic stress disorder (PTSD) is an anxiety disorder triggered by traumatic events. Symptoms include anxiety, depression and deficits in fear memory extinction (FE). PTSD patients show a higher prevalence of cigarette smoking than the general population. The present study investigated the effects of cotinine, a tobacco-derived compound, over anxiety and contextual fear memory after fear conditioning (FC) in mice, a model for inducing PTSD-like symptoms. Two-month-old C57BL/6J mice were separated into three experimental groups. These groups were used to investigate the effect of pretreatment with cotinine on contextual fear memory and posttreatment on extinction and stability or retrievability of the fear memory. Also, changes induced by cotinine on the expression of extracellular signal-regulated kinase (ERK)1/2 were assessed after extinction in the hippocampus. An increase in anxiety and corticosterone levels were found after fear conditioning. Cotinine did not affect corticosterone levels but enhanced the extinction of contextual fear, decreased anxiety and the stability and/or retrievability of contextual fear memory. Cotinine-treated mice showed higher levels of the active forms of ERK1/2 than vehicle-treated mice after FC. This evidence suggests that cotinine is a potential new pharmacological treatment to reduce symptoms in individuals with PTSD.

  3. Worrying affects associative fear learning: a startle fear conditioning study

    NARCIS (Netherlands)

    F.J. Gazendam; M. Kindt

    2012-01-01

    A valuable experimental model for the pathogenesis of anxiety disorders is that they originate from a learned association between an intrinsically non-aversive event (Conditioned Stimulus, CS) and an anticipated disaster (Unconditioned Stimulus, UCS). Most anxiety disorders, however, do not evolve f

  4. Reinstatement of extinguished fear by an unextinguished conditional stimulus

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    Lindsay R Halladay

    2012-05-01

    Full Text Available Anxiety disorders are often treated using extinction-based exposure therapy, but relapse is common and can occur as a result of reinstatement, whereby an aversive trigger can reinstate extinguished fear. Animal models of reinstatement commonly utilize a Pavlovian fear conditioning procedure, in which subjects are first trained to fear a conditional stimulus (CS by pairing it with an aversive unconditional stimulus (US, and then extinguished by repeated presentations of the CS alone. Reinstatement is typically induced by exposing subjects to an aversive US after extinction, but here we show that exposure to a non-extinguished CS can reinstate conditional fear responding to an extinguished CS, a phenomenon we refer to as conditional reinstatement. Rats were trained to fear two CSs (light and tone and subsequently underwent extinction training to only one CS (counterbalanced. Presenting the unextinguished CS (but not a novel cue immediately after extinction reinstated conditional fear responding to the extinguished CS in a test session given 24h later. These findings indicate that reinstatement of extinguished fear can be triggered by exposure to conditional as well as unconditional aversive stimuli, and this may help to explain why relapse is common following clinical extinction therapy in humans. Further study of conditional reinstatement using animal models may prove useful for developing refined extinction therapies that are more resistant to reinstatement.

  5. Classical Conditioning: Eliciting the Right Response.

    Science.gov (United States)

    Tauber, Robert T.

    1990-01-01

    Classical conditioning is responsible for students' positive and negative feelings, whether directed toward subject matter, peers, teachers, or education in general. This article explains how educators can use classical conditioning principles (such as reinforcement, extinction, and paired stimuli) to create an anxiety-free learning environment.…

  6. Skin conductance fear conditioning impairments and aggression: a longitudinal study.

    Science.gov (United States)

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

    2015-02-01

    Autonomic fear conditioning deficits have been linked to child aggression and adult criminal behavior. However, it is unknown if fear conditioning deficits are specific to certain subtypes of aggression, and longitudinal research is rare. In the current study, reactive and proactive aggression were assessed in a sample of males and females when aged 10, 12, 15, and 18 years old. Skin conductance fear conditioning data were collected when they were 18 years old. Individuals who were persistently high on proactive aggression measures had significantly poorer conditioned responses at 18 years old when compared to others. This association was not found for reactive aggression. Consistent with prior literature, findings suggest that persistent antisocial individuals have unique neurobiological characteristics and that poor autonomic fear conditioning is associated with the presence of increased instrumental aggressive behavior.

  7. Fear conditioning-related changes in cerebellar Purkinje cell activities in goldfish

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    Yoshida Masayuki

    2012-10-01

    Full Text Available Abstract Background Fear conditioning-induced changes in cerebellar Purkinje cell responses to a conditioned stimulus have been reported in rabbits. It has been suggested that synaptic long-term potentiation and the resulting increases in firing rates of Purkinje cells are related to the acquisition of conditioned fear in mammals. However, Purkinje cell activities during acquisition of conditioned fear have not been analysed, and changes in Purkinje cell activities throughout the development of conditioned fear have not yet been investigated. In the present study, we tracked Purkinje cell activities throughout a fear conditioning procedure and aimed to elucidate further how cerebellar circuits function during the acquisition and expression of conditioned fear. Methods Activities of single Purkinje cells in the corpus cerebelli were tracked throughout a classical fear conditioning procedure in goldfish. A delayed conditioning paradigm was used with cardiac deceleration as the conditioned response. Conditioning-related changes of Purkinje cell responses to a conditioned stimulus and unconditioned stimulus were examined. Results The majority of Purkinje cells sampled responded to the conditioned stimulus by either increasing or decreasing their firing rates before training. Although there were various types of conditioning-related changes in Purkinje cells, more than half of the cells showed suppressed activities in response to the conditioned stimulus after acquisition of conditioned fear. Purkinje cells that showed unconditioned stimulus-coupled complex-spike firings also exhibited conditioning-related suppression of simple-spike responses to the conditioned stimulus. A small number of Purkinje cells showed increased excitatory responses in the acquisition sessions. We found that the magnitudes of changes in the firing frequencies of some Purkinje cells in response to the conditioned stimulus correlated with the magnitudes of the conditioned

  8. Stress differentially affects fear conditioning in men and women.

    Science.gov (United States)

    Merz, Christian Josef; Wolf, Oliver Tobias; Schweckendiek, Jan; Klucken, Tim; Vaitl, Dieter; Stark, Rudolf

    2013-11-01

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

  9. Social transmission of Pavlovian fear: fear-conditioning by-proxy in related female rats.

    Science.gov (United States)

    Jones, Carolyn E; Riha, Penny D; Gore, Andrea C; Monfils, Marie-H

    2014-05-01

    Pairing a previously neutral conditioned stimulus (CS; e.g., a tone) to an aversive unconditioned stimulus (US; e.g., a foot-shock) leads to associative learning such that the tone alone will elicit a conditioned response (e.g., freezing). Individuals can also acquire fear from a social context, such as through observing the fear expression of a conspecific. In the current study, we examined the influence of kinship/familiarity on social transmission of fear in female rats. Rats were housed in triads with either sisters or non-related females. One rat from each cage was fear conditioned to a tone CS+ shock US. On day two, the conditioned rat was returned to the chamber accompanied by one of her cage mates. Both rats were allowed to behave freely, while the tone was played in the absence of the foot-shock. The previously untrained rat is referred to as the fear-conditioned by-proxy (FCbP) animal, as she would freeze based on observations of her cage-mate's response rather than due to direct personal experience with the foot-shock. The third rat served as a cage-mate control. The third day, long-term memory tests to the CS were performed. Consistent with our previous application of this paradigm in male rats (Bruchey et al. in Behav Brain Res 214(1):80-84, 2010), our results revealed that social interactions between the fear conditioned and FCbP rats on day two contribute to freezing displayed by the FCbP rats on day three. In this experiment, prosocial behavior occurring at the termination of the cue on day two was significantly greater between sisters than their non-sister counterparts, and this behavior resulted in increased freezing on day three. Our results suggest that familiarity and/or kinship influences the social transmission of fear in female rats.

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

    Science.gov (United States)

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

    2015-05-01

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

  11. Psychopaths Show Enhanced Amygdala Activation during Fear Conditioning.

    Science.gov (United States)

    Schultz, Douglas H; Balderston, Nicholas L; Baskin-Sommers, Arielle R; Larson, Christine L; Helmstetter, Fred J

    2016-01-01

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

  12. Psychopaths show enhanced amygdala activation during fear conditioning

    Directory of Open Access Journals (Sweden)

    Douglas eSchultz

    2016-03-01

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

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

    Science.gov (United States)

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

    2015-06-01

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

  14. Social buffering ameliorates conditioned fear responses in female rats.

    Science.gov (United States)

    Ishii, Akiko; Kiyokawa, Yasushi; Takeuchi, Yukari; Mori, Yuji

    2016-05-01

    The stress experienced by an animal is ameliorated when the animal is exposed to distressing stimuli along with a conspecific animal(s). This is known as social buffering. Previously, we found that the presence of an unfamiliar male rat induced social buffering and ameliorated conditioned fear responses of a male rat subjected to an auditory conditioned stimulus (CS). However, because our knowledge of social buffering is highly biased towards findings in male subjects, analyses using female subjects are crucial for comprehensively understanding the social buffering phenomenon. In the present studies, we assessed social buffering of conditioned fear responses in female rats. We found that the estrus cycle did not affect the intensity of the rats' fear responses to the CS or their degree of vigilance due to the presence of a conspecific animal. Based on these findings, we then assessed whether social buffering ameliorated conditioned fear responses in female rats without taking into account their estrus cycles. When fear conditioned female rats were exposed to the CS without the presence of a conspecific, they exhibited behavioral responses, including freezing, and elevated corticosterone levels. By contrast, the presence of an unfamiliar female rat suppressed these responses. Based on these findings, we conclude that social buffering can ameliorate conditioned fear responses in female rats.

  15. Delayed effects of cortisol enhance fear memory of trace conditioning.

    Science.gov (United States)

    Cornelisse, Sandra; van Ast, Vanessa A; Joëls, Marian; Kindt, Merel

    2014-02-01

    Corticosteroids induce rapid non-genomic effects followed by slower genomic effects that are thought to modulate cognitive function in opposite and complementary ways. It is presently unknown how these time-dependent effects of cortisol affect fear memory of delay and trace conditioning. This distinction is of special interest because the neural substrates underlying these types of conditioning may be differently affected by time-dependent cortisol effects. Delay conditioning is predominantly amygdala-dependent, while trace conditioning additionally requires the hippocampus. Here, we manipulated the timing of cortisol action during acquisition of delay and trace fear conditioning, by randomly assigning 63 men to one of three possible groups: (1) receiving 10mg hydrocortisone 240 min (slow cort) or (2) 60 min (rapid cort) before delay and trace acquisition, or (3) placebo at both times, in a double-blind design. The next day, we tested memory for trace and delay conditioning. Fear potentiated startle responses, skin conductance responses and unconditioned stimulus expectancy scores were measured throughout the experiment. The fear potentiated startle data show that cortisol intake 240 min before actual fear acquisition (slow cort) uniquely strengthened subsequent trace conditioned memory. No effects of cortisol delivery 60 min prior to fear acquisition were found on any measure of fear memory. Our findings emphasize that slow, presumably genomic, but not more rapid effects of corticosteroids enhance hippocampal-dependent fear memories. On a broader level, our findings underline that basic experimental research and clinically relevant pharmacological treatments employing corticosteroids should acknowledge the timing of corticosteroid administration relative to the learning phase, or therapeutic intervention.

  16. The Role of Contingency in Classical Conditioning.

    Science.gov (United States)

    Papini, Mauricio R.; Bitterman, M. E.

    1990-01-01

    Early experiments suggesting that classical conditioning depends on the contingency between conditioned stimulus (CS) and the unconditioned stimulus (US) are reconsidered along with later evidence that shows conditioning of the CS and its context in random training. CS-US contingency is neither necessary nor sufficient for conditioning. (SLD)

  17. Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning.

    Science.gov (United States)

    Catlow, Briony J; Song, Shijie; Paredes, Daniel A; Kirstein, Cheryl L; Sanchez-Ramos, Juan

    2013-08-01

    Drugs that modulate serotonin (5-HT) synaptic concentrations impact neurogenesis and hippocampal (HPC)-dependent learning. The primary objective is to determine the extent to which psilocybin (PSOP) modulates neurogenesis and thereby affects acquisition and extinction of HPC-dependent trace fear conditioning. PSOP, the 5-HT2A agonist 25I-NBMeO and the 5-HT2A/C antagonist ketanserin were administered via an acute intraperitoneal injection to mice. Trace fear conditioning was measured as the amount of time spent immobile in the presence of the conditioned stimulus (CS, auditory tone), trace (silent interval) and post-trace interval over 10 trials. Extinction was determined by the number of trials required to resume mobility during CS, trace and post-trace when the shock was not delivered. Neurogenesis was determined by unbiased counts of cells in the dentate gyrus of the HPC birth-dated with BrdU co-expressing a neuronal marker. Mice treated with a range of doses of PSOP acquired a robust conditioned fear response. Mice injected with low doses of PSOP extinguished cued fear conditioning significantly more rapidly than high-dose PSOP or saline-treated mice. Injection of PSOP, 25I-NBMeO or ketanserin resulted in significant dose-dependent decreases in number of newborn neurons in hippocampus. At the low doses of PSOP that enhanced extinction, neurogenesis was not decreased, but rather tended toward an increase. Extinction of "fear conditioning" may be mediated by actions of the drugs at sites other than hippocampus such as the amygdala, which is known to mediate the perception of fear. Another caveat is that PSOP is not purely selective for 5-HT2A receptors. PSOP facilitates extinction of the classically conditioned fear response, and this, and similar agents, should be explored as potential treatments for post-traumatic stress disorder and related conditions.

  18. Increased tone-offset response in the lateral nucleus of the amygdala underlies trace fear conditioning.

    Science.gov (United States)

    Kim, Namsoo; Kong, Mi-Seon; Jo, Kyeong Im; Kim, Eun Joo; Choi, June-Seek

    2015-12-01

    Accumulating evidence suggests that the lateral nucleus of the amygdala (LA) stores associative memory in the form of enhanced neural response to the sensory input following classical fear conditioning in which the conditioned stimulus (CS) and the unconditioned stimulus (US) are presented in a temporally continuous manner. However, little is known about the role of the LA in trace fear conditioning where the CS and the US are separated by a temporal gap. Single-unit recordings of LA neurons before and after trace fear conditioning revealed that the short-latency activity to the CS offset, but not that to the onset, increased significantly and accompanied the conditioned fear response. The increased short-latency activity was evident in two aspects: the number of offset-responsive neurons was increased and the latency of the neuronal response to the CS offset was shortened. On the contrary, changes in the firing rate to either the onset or the offset were negligible following unpaired presentations of the CS and US. In sum, our results suggest that increased synaptic efficacy in the CS offset pathway in the LA might underlie the association between temporally distant stimuli in trace fear conditioning.

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Oliveira M.G.M.

    1998-01-01

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

  1. Categories, concepts, and conditioning: how humans generalize fear.

    Science.gov (United States)

    Dunsmoor, Joseph E; Murphy, Gregory L

    2015-02-01

    During the past century, Pavlovian conditioning has served as the predominant experimental paradigm and theoretical framework to understand how humans learn to fear and avoid real or perceived dangers. Animal models for translational research offer insight into basic behavioral and neurophysiological factors mediating the acquisition, expression, inhibition, and generalization of fear. However, it is important to consider the limits of traditional animal models when applied to humans. Here, we focus on the question of how humans generalize fear. We propose that to understand fear generalization in humans requires taking into account research on higher-level cognition such as category-based induction, inferential reasoning, and representation of conceptual knowledge. Doing so will open the door for productive avenues of new research.

  2. Human fear conditioning and extinction in neuroimaging: a systematic review.

    Directory of Open Access Journals (Sweden)

    Christina Sehlmeyer

    Full Text Available Fear conditioning and extinction are basic forms of associative learning that have gained considerable clinical relevance in enhancing our understanding of anxiety disorders and facilitating their treatment. Modern neuroimaging techniques have significantly aided the identification of anatomical structures and networks involved in fear conditioning. On closer inspection, there is considerable variation in methodology and results between studies. This systematic review provides an overview of the current neuroimaging literature on fear conditioning and extinction on healthy subjects, taking into account methodological issues such as the conditioning paradigm. A Pubmed search, as of December 2008, was performed and supplemented by manual searches of bibliographies of key articles. Two independent reviewers made the final study selection and data extraction. A total of 46 studies on cued fear conditioning and/or extinction on healthy volunteers using positron emission tomography or functional magnetic resonance imaging were reviewed. The influence of specific experimental factors, such as contingency and timing parameters, assessment of conditioned responses, and characteristics of conditioned and unconditioned stimuli, on cerebral activation patterns was examined. Results were summarized descriptively. A network consisting of fear-related brain areas, such as amygdala, insula, and anterior cingulate cortex, is activated independently of design parameters. However, some neuroimaging studies do not report these findings in the presence of methodological heterogeneities. Furthermore, other brain areas are differentially activated, depending on specific design parameters. These include stronger hippocampal activation in trace conditioning and tactile stimulation. Furthermore, tactile unconditioned stimuli enhance activation of pain related, motor, and somatosensory areas. Differences concerning experimental factors may partly explain the variance

  3. Appetitive-aversive interactions in Pavlovian fear conditioning.

    Science.gov (United States)

    Nasser, Helen M; McNally, Gavan P

    2012-06-01

    The existence of value coding and salience coding neurons in the mammalian brain, including in habenula and ventral tegmental area, has sparked considerable interest in the interactions that occur between Pavlovian appetitive and aversive conditioning. Here we studied these appetitive-aversive interactions at the behavioral level by assessing the learning that occurs when a Pavlovian appetitive conditioned stimulus (conditional stimulus, CS) serves as a CS for shock in Pavlovian fear conditioning. A Pavlovian appetitive CS was retarded in the rate at which it could be transformed into a fear CS (counterconditioning), but the presence of the appetitive CS augmented fear learning to a concurrently presented neutral CS (superconditioning). Retardation of fear learning was not alleviated by manipulations designed to restore the associability of the appetitive CS before fear conditioning but was alleviated by manipulations designed to increase the aversive quality of the shock unconditioned stimulus (US). These findings are consistent with opponent interactions between the appetitive and aversive motivational systems and provide a behavioral approach for assessing the neural correlates of these appetitive-aversive interactions.

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

    Directory of Open Access Journals (Sweden)

    Lisa eBulganin

    2014-03-01

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

  5. Conditional reasoning and phobic fear : Evidence for a fear-confirming reasoning pattern

    NARCIS (Netherlands)

    de Jong, Peter; Mayer, B; vandenHout, M

    1997-01-01

    In two experiments we explored the role of subjects' reasoning performance in the persistence of phobic fear. More specifically, we investigated whether (phobic) subjects are prone to selectively search for danger-confirming information when asked to judge the validity of conditional rules in the co

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

    Science.gov (United States)

    Fullana, M A; Harrison, B J; Soriano-Mas, C; Vervliet, B; Cardoner, N; Àvila-Parcet, A; Radua, J

    2016-04-01

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

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

    Science.gov (United States)

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

    2015-11-01

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

  8. Fear conditioning, safety learning, and sleep in humans.

    Science.gov (United States)

    Marshall, Anisa J; Acheson, Dean T; Risbrough, Victoria B; Straus, Laura D; Drummond, Sean P A

    2014-08-27

    Fear conditioning is considered an animal model of post-traumatic stress disorder. Such models have shown fear conditioning disrupts subsequent rapid eye movement sleep (REM). Here, we provide a translation of these models into humans. Using the fear potentiated startle (FPS) procedure, we examined the effects of fear conditioning and safety signal learning on subsequent REM sleep in healthy adults. We also examined the effects of changes in REM sleep on retention of fear and safety learning. Participants (n = 42 normal controls) spent 3 consecutive nights in the laboratory. The first was an adaptation night. Following the second night, we administered a FPS procedure that included pairing a wrist shock with a threat signal and a safety signal never paired with a shock. The next day, we administered the FPS procedure again, with no wrist shocks to any stimulus, to measure retention of fear and safety. Canonical correlations assessed the relationship between FPS response and REM sleep. Results demonstrated that increased safety signal learning during the initial acquisition phase was associated with increased REM sleep consolidation that night, with 28.4% of the variance in increased REM sleep consolidation from baseline accounted for by safety signal learning. Overnight REM sleep was, in turn, related to overnight retention of fear and safety learning, with 22.5% of the variance in startle retention accounted for by REM sleep. These data suggest that sleep difficulties, specifically REM sleep fragmentation, may play a mechanistic role in post-traumatic stress disorder via an influence on safety signal learning and/or threat-safety discrimination.

  9. Contextual fear conditioning differs for infant, adolescent, and adult rats.

    Science.gov (United States)

    Esmorís-Arranz, Francisco J; Méndez, Cástor; Spear, Norman E

    2008-07-01

    Contextual fear conditioning was tested in infant, adolescent, and adult rats in terms of Pavlovian-conditioned suppression. When a discrete auditory-conditioned stimulus (CS) was paired with footshock (unconditioned stimulus, US) within the largely olfactory context, infants and adolescents conditioned to the context with substantial effectiveness, but adult rats did not. When unpaired presentations of the CS and US occurred within the context, contextual fear conditioning was strong for adults, weak for infants, but about as strong for adolescents as when pairings of CS and US occurred in the context. Nonreinforced presentations of either the CS or context markedly reduced contextual fear conditioning in infants, but, in adolescents, CS extinction had no effect on contextual fear conditioning, although context extinction significantly reduced it. Neither CS extinction nor context extinction affected responding to the CS-context compound in infants, suggesting striking discrimination between the compound and its components. Female adolescents showed the same lack of effect of component extinction on response to the compound as infants, but CS extinction reduced responding to the compound in adolescent males, a sex difference seen also in adults. Theoretical implications are discussed for the development of perceptual-cognitive processing and hippocampus role.

  10. Teens that fear screams: A comparison of fear conditioning, extinction, and reinstatement in adolescents and adults.

    Science.gov (United States)

    Den, Miriam Liora; Graham, Bronwyn M; Newall, Carol; Richardson, Rick

    2015-11-01

    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.

  11. Attitudes of Children Established by Classical Conditioning.

    Science.gov (United States)

    Barnabei, Fred; And Others

    This study examined the attitudes of children established by classical conditioning. Subjects were 4th graders (26 males and 31 females). Each child was randomly assigned to either an experimental or a control group. A posttest-only design was used with positive and negative word associations presented to the experimental group, and neutral word…

  12. Priority in the Classical Conditioning of Children.

    Science.gov (United States)

    Windholz, George; Lamal, P. A.

    1986-01-01

    Contrary to widely held belief, Watons and Rayner's (1920) experiment with Little Albert is not first reported case of classical conditioning of a child. Their work was preceded by that of Bogen and of Krasnogorskii. Mateer's work either preceded or coincided with Watons and Rayner's. This article clarifies chronology of these early studies of…

  13. Stimulus Configuration, Classical Conditioning, and Hippocampal Function.

    Science.gov (United States)

    Schmajuk, Nestor A.; DiCarlo, James J.

    1991-01-01

    The participation of the hippocampus in classical conditioning is described in terms of a multilayer network portraying stimulus configuration. A model of hippocampal function is presented, and computer simulations are used to study neural activity in the various brain areas mapped according to the model. (SLD)

  14. Don't fear 'fear conditioning': Methodological considerations for the design and analysis of studies on human fear acquisition, extinction, and return of fear.

    Science.gov (United States)

    Lonsdorf, Tina B; Menz, Mareike M; Andreatta, Marta; Fullana, Miguel A; Golkar, Armita; Haaker, Jan; Heitland, Ivo; Hermann, Andrea; Kuhn, Manuel; Kruse, Onno; Drexler, Shira Meir; Meulders, Ann; Nees, Frauke; Pittig, Andre; Richter, Jan; Römer, Sonja; Shiban, Youssef; Schmitz, Anja; Straube, Benjamin; Vervliet, Bram; Wendt, Julia; Baas, Johanna M P; Merz, Christian J

    2017-03-03

    The so-called 'replicability crisis' has sparked methodological discussions in many areas of science in general, and in psychology in particular. This has led to recent endeavours to promote the transparency, rigour, and ultimately, replicability of research. Originating from this zeitgeist, the challenge to discuss critical issues on terminology, design, methods, and analysis considerations in fear conditioning research is taken up by this work, which involved representatives from fourteen of the major human fear conditioning laboratories in Europe. This compendium is intended to provide a basis for the development of a common procedural and terminology framework for the field of human fear conditioning. Whenever possible, we give general recommendations. When this is not feasible, we provide evidence-based guidance for methodological decisions on study design, outcome measures, and analyses. Importantly, this work is also intended to raise awareness and initiate discussions on crucial questions with respect to data collection, processing, statistical analyses, the impact of subtle procedural changes, and data reporting specifically tailored to the research on fear conditioning.

  15. Secondary extinction in Pavlovian fear conditioning.

    Science.gov (United States)

    Vurbic, Drina; Bouton, Mark E

    2011-09-01

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

  16. Delayed effects of cortisol enhance fear memory of trace conditioning

    NARCIS (Netherlands)

    Cornelisse, S.; Ast, V.A. van; Joëls, M.; Kindt, M.

    2014-01-01

    Corticosteroids induce rapid non-genomic effects followed by slower genomic effects that are thought to modulate cognitive function in opposite and complementary ways. It is presently unknown how these time-dependent effects of cortisol affect fear memory of delay and trace conditioning. This distin

  17. High-dose corticosterone after fear conditioning selectively suppresses fear renewal by reducing anxiety-like response.

    Science.gov (United States)

    Wang, Hongbo; Xing, Xiaoli; Liang, Jing; Bai, Yunjing; Lui, Zhengkui; Zheng, Xigeng

    2014-09-01

    Exposure therapy is widely used to treat anxiety disorders, including posttraumatic stress disorder (PTSD). However, preventing the return of fear is still a major challenge after this behavioral treatment. An increasing number of studies suggest that high-dose glucocorticoid treatment immediately after trauma can alleviate the symptoms of PTSD in humans. Unknown is whether high-dose glucocorticoid treatment following fear conditioning suppresses the return of fear. In the present study, a typical fear renewal paradigm (AAB) was used, in which the fear response to an auditory cue can be restored in a novel context (context B) when both training and extinction occur in the same context (context A). We trained rats for auditory fear conditioning and administered corticosterone (CORT; 5 and 25mg/kg, i.p.) or vehicle with different delays (1 and 24h). Forty-eight hours after drug injection, extinction was conducted with no drug in the training context, followed by a test of tone-induced freezing behavior in the same (AAA) or a shifted (AAB) context. Both immediate and delayed administration of high-dose CORT after fear conditioning reduced fear renewal. To examine the anxiolytic effect of CORT, independent rats were trained for cued or contextual fear conditioning, followed by an injection of CORT (5 and 25mg/kg, i.p.) or vehicle at a 1 or 24h delay. One week later, anxiety-like behavior was assessed in the elevated plus maze (EPM) before and after fear expression. We found that high-dose CORT decreased anxiety-like behavior without changing tone- or context-induced freezing. These findings indicate that a single high-dose CORT administration given after fear conditioning may selectively suppress fear renewal by reducing anxiety-like behavior and not by altering the consolidation, retrieval, or extinction of fear memory.

  18. Adolescent traumatic stress experience results in less robust conditioned fear and post-extinction fear cue responses in adult rats.

    Science.gov (United States)

    Moore, Nicole L T; Gauchan, Sangeeta; Genovese, Raymond F

    2014-05-01

    Early exposure to a traumatic event may produce lasting effects throughout the lifespan. Traumatic stress during adolescence may deliver a distinct developmental insult compared with more-often studied neonatal or juvenile traumatic stress paradigms. The present study describes the lasting effects of adolescent traumatic stress upon adulthood fear conditioning. Adolescent rats were exposed to a traumatic stressor (underwater trauma, UWT), then underwent fear conditioning during adulthood. Fear extinction was tested over five conditioned suppression extinction sessions three weeks later. The efficacies of two potential extinction-enhancing compounds, endocannabinoid reuptake inhibitor AM404 (10mg/kg) and M1 muscarinic positive allosteric modulator BQCA (10mg/kg), were also assessed. Finally, post-extinction fear responses were examined using a fear cue (light) as a prepulse stimulus. Rats traumatically stressed during adolescence showed blunted conditioned suppression on day 1 of extinction training, and AM404 reversed this effect. Post-extinction startle testing showed that fear conditioning eliminates prepulse inhibition to the light cue. Startle potentiation was observed only in rats without adolescent UWT exposure. AM404 and BQCA both ameliorated this startle potentiation, while BQCA increased startle in the UWT group. These results suggest that exposure to a traumatic stressor during adolescence alters developmental outcomes related to stress response and fear extinction compared to rats without adolescent traumatic stress exposure, blunting the adulthood fear response and reducing residual post-extinction fear expression. Efficacy of pharmacological interventions may also vary as a factor of developmental traumatic stress exposure.

  19. Coantagonism of Glutamate Receptors and Nicotinic Acetylcholinergic Receptors Disrupts Fear Conditioning and Latent Inhibition of Fear Conditioning

    Science.gov (United States)

    Gould, Thomas J.; Lewis, Michael C.

    2005-01-01

    The present study investigated the hypothesis that both nicotinic acetylcholinergic receptors (nAChRs) and glutamate receptors ([alpha]-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors (AMPARs) and N-methyl-D-aspartate glutamate receptors (NMDARs)) are involved in fear conditioning, and may modulate similar processes. The effects of the…

  20. Dual functions of perirhinal cortex in fear conditioning.

    Science.gov (United States)

    Kent, Brianne A; Brown, Thomas H

    2012-10-01

    The present review examines the role of perirhinal cortex (PRC) in Pavlovian fear conditioning. The focus is on rats, partly because so much is known, behaviorally and neurobiologically, about fear conditioning in these animals. In addition, the neuroanatomy and neurophysiology of rat PRC have been described in considerable detail at the cellular and systems levels. The evidence suggests that PRC can serve at least two types of mnemonic functions in Pavlovian fear conditioning. The first function, termed "stimulus unitization," refers to the ability to treat two or more separate items or stimulus elements as a single entity. Supporting evidence for this perceptual function comes from studies of context conditioning as well as delay conditioning to discontinuous auditory cues. In a delay paradigm, the conditional stimulus (CS) and unconditional stimulus (US) overlap temporally and co-terminate. The second PRC function entails a type of "transient memory." Supporting evidence comes from studies of trace cue conditioning, where there is a temporal gap or trace interval between the CS offset and the US onset. For learning to occur, there must be a transient CS representation during the trace interval. We advance a novel neurophysiological mechanism for this transient representation. These two hypothesized functions of PRC are consistent with inferences based on non-aversive forms of learning.

  1. Better fear conditioning is associated with reduced symptom severity in autism spectrum disorders.

    Science.gov (United States)

    South, Mikle; Larson, Michael J; White, Sarah E; Dana, Julianne; Crowley, Michael J

    2011-12-01

    Evidence from behavioral and neuroimaging studies suggest that atypical amygdala function plays a critical role in the development of autism spectrum disorders (ASD). The handful of psychophysiological studies examining amygdala function in ASD using classical fear conditioning paradigms have yielded discordant results. We recorded skin conductance response (SCR) during a simple discrimination conditioning task in 30 children and adolescents (ages 8-18) diagnosed with high-functioning ASD and 30 age- and IQ-matched, typically developing controls. SCR response in the ASD group was uniquely and positively associated with social anxiety; and negatively correlated with autism symptom severity, in particular with social functioning. Fear conditioning studies have tremendous potential to aid understanding regarding the amygdale's role in the varied symptom profile of ASD. Our data demonstrate that such studies require careful attention to task-specific factors, including task complexity; and also to contributions of dimensional, within-group factors that contribute to ASD heterogeneity.

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

    Science.gov (United States)

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

    2016-07-15

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

  3. Bidirectional synaptic plasticity in intercalated amygdala neurons and the extinction of conditioned fear responses.

    Science.gov (United States)

    Royer, S; Paré, D

    2002-01-01

    Classical fear conditioning is believed to result from potentiation of conditioned synaptic inputs in the basolateral amygdala. That is, the conditioned stimulus would excite more neurons in the central nucleus and, via their projections to the brainstem and hypothalamus, evoke fear responses. However, much data suggests that extinction of fear responses does not depend on the reversal of these changes but on a parallel NMDA-dependent learning that competes with the first one. Because they control impulse traffic from the basolateral amygdala to the central nucleus, GABAergic neurons of the intercalated cell masses are ideally located to implement this second learning. Consistent with this hypothesis, the present study shows that low- and high-frequency stimulation of basolateral afferents respectively induce long-term depression (LTD) and potentiation (LTP) of responses in intercalated cells. Moreover, induction of LTP and LTD is prevented by application of an NMDA antagonist. To determine how these activity-dependent changes are expressed, we tested whether LTD and LTP induction are associated with modifications in paired-pulse facilitation, an index of transmitter release probability. Only LTP induction was associated with a change in paired-pulse facilitation. Depotentiation of previously potentiated synapses did not revert the modification in paired pulse facilitation, suggesting that LTP is associated with presynaptic alterations, but that LTD and depotentiation depend on postsynaptic changes. Taken together, our results suggest that basolateral synapses onto intercalated neurons can express NMDA-dependent LTP and LTD, consistent with the possibility that intercalated neurons are a critical locus of plasticity for the extinction of conditioned fear responses. Ultimately, these plastic events may prevent conditioned amygdala responses from exciting neurons of the central nucleus, and thus from evoking conditioned fear responses.

  4. Eyeblink classical conditioning in the preweanling lamb.

    Science.gov (United States)

    Johnson, Timothy B; Stanton, Mark E; Goodlett, Charles R; Cudd, Timothy A

    2008-06-01

    Classical conditioning of eyeblink responses has been one of the most important models for studying the neurobiology of learning, with many comparative, ontogenetic, and clinical applications. The current study reports the development of procedures to conduct eyeblink conditioning in preweanling lambs and demonstrates successful conditioning using these procedures. These methods will permit application of eyeblink conditioning procedures in the analysis of functional correlates of cerebellar damage in a sheep model of fetal alcohol spectrum disorders, which has significant advantages over more common laboratory rodent models. Because sheep have been widely used for studies of pathogenesis and mechanisms of injury with many different prenatal or perinatal physiological insults, eyeblink conditioning can provide a well-studied method to assess postnatal behavioral outcomes, which heretofore have not typically been pursued with ovine models of developmental insults.

  5. Demand Characteristics in Classical Verbal Conditioning and Attitude Conditioning Studies.

    Science.gov (United States)

    McGinley, Hugh

    This paper is a draft for the American Psychological Association Symposium on the conditioning of verbal behavior and attitudes. The author presents the results of several studies he conducted in the classical conditioning of meaning and attitude. These studies attempt to control the measurement effects created by extraneous variables operating on…

  6. Evaluating the TD model of classical conditioning.

    Science.gov (United States)

    Ludvig, Elliot A; Sutton, Richard S; Kehoe, E James

    2012-09-01

    The temporal-difference (TD) algorithm from reinforcement learning provides a simple method for incrementally learning predictions of upcoming events. Applied to classical conditioning, TD models suppose that animals learn a real-time prediction of the unconditioned stimulus (US) on the basis of all available conditioned stimuli (CSs). In the TD model, similar to other error-correction models, learning is driven by prediction errors--the difference between the change in US prediction and the actual US. With the TD model, however, learning occurs continuously from moment to moment and is not artificially constrained to occur in trials. Accordingly, a key feature of any TD model is the assumption about the representation of a CS on a moment-to-moment basis. Here, we evaluate the performance of the TD model with a heretofore unexplored range of classical conditioning tasks. To do so, we consider three stimulus representations that vary in their degree of temporal generalization and evaluate how the representation influences the performance of the TD model on these conditioning tasks.

  7. Spectral characteristics of the hippocampal LFP during contextual fear conditioning

    OpenAIRE

    2012-01-01

    OBJECTIVE: The hippocampus has an important role in the acquisition and recall of aversive memories. The objective of this study was to investigate the relationship among hippocampal rhythms. METHODS: Microeletrodes arrays were implanted in the hippocampus of Wistar rats. The animals were trained and tested in a contextual fear conditioning task. The training consisted in applying shocks in the legs. The memory test was performed 1 day (recent memory) or 18 days (remote memory) after training...

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

    NARCIS (Netherlands)

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

    1999-01-01

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

  9. Classical conditioned responses to absent tones

    Directory of Open Access Journals (Sweden)

    Häusler Udo

    2006-08-01

    Full Text Available Abstract Background Recent evidence for a tight coupling of sensorimotor processes in trained musicians led to the question of whether this coupling extends to preattentively mediated reflexes; particularly, whether a classically conditioned response in one of the domains (auditory is generalized to another (tactile/motor on the basis of a prior association in a second-order Pavlovian paradigm. An eyeblink conditioning procedure was performed in 17 pianists, serving as a model for overlearned audiomotor integration, and 14 non-musicians. Results: During the training session, subjects were conditioned to respond to auditory stimuli (piano tones. During a subsequent testing session, when subjects performed keystrokes on a silent piano, pianists showed significantly higher blink rates than non-musicians. Conclusion These findings suggest a tight coupling of the auditory and motor domains in musicians, pointing towards training-dependent mechanisms of strong cross-modal sensorimotor associations even on sub-cognitive processing levels.

  10. Classical eyeblink conditioning in Parkinson's disease.

    Science.gov (United States)

    Daum, I; Schugens, M M; Breitenstein, C; Topka, H; Spieker, S

    1996-11-01

    Patients with Parkinson's disease (PD) show impairments of a range of motor learning tasks, including tracking or serial reaction time task learning. Our study investigated whether such deficits would also be seen on a simple type of motor learning, classic conditioning of the eyeblink response. Medicated and unmediated patients with PD showed intact unconditioned eyeblink responses and significant learning across acquisition; the learning rates did not differ from those of healthy control subjects. The overall frequency of conditioned responses was significantly higher in the medicated patients with PD relative to control subjects, and there was also some evidence of facilitation in the unmedicated patients with PD. Conditioning of electrodermal and electrocortical responses was comparable in all groups. The findings are discussed in terms of enhanced excitability of brainstem pathways in PD and of the involvement of different neuronal circuits in different types of motor learning.

  11. Energy conditions and classical scalar fields

    CERN Document Server

    Bellucci, S

    2002-01-01

    Attention has been recently called upon the fact that the weak and null energy conditions and the second law of thermodynamics are violated in wormhole solutions of Einstein's theory with classical, nonminimally coupled, scalar fields as material source. It is shown that the discussion is only meaningful when ambiguities in the definitions of stress-energy tensor and energy density of a nonminimally coupled scalar are resolved. The three possible approaches are discussed with emphasis on the positivity of the respective energy densities and covariant conservation laws. The root of the ambiguities is traced to the energy localization problem for the gravitational field.

  12. A role for midline and intralaminar thalamus in the associative blocking of Pavlovian fear conditioning.

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    Sengupta, Auntora; McNally, Gavan P

    2014-01-01

    Fear learning occurs in response to positive prediction error, when the expected outcome of a conditioning trial exceeds that predicted by the conditioned stimuli present. This role for error in Pavlovian association formation is best exemplified by the phenomenon of associative blocking, whereby prior fear conditioning of conditioned stimulus (CS) A is able to prevent learning to CSB when they are conditioned in compound. The midline and intralaminar thalamic nuclei (MIT) are well-placed to contribute to fear prediction error because they receive extensive projections from the midbrain periaqueductal gray-which has a key role in fear prediction error-and project extensively to prefrontal cortex and amygdala. Here we used an associative blocking design to study the role of MIT in fear learning. In Stage I rats were trained to fear CSA via pairings with shock. In Stage II rats received compound fear conditioning of CSAB paired with shock. On test, rats that received Stage I training expressed less fear to CSB relative to control rats that did not receive this training. Microinjection of bupivacaine into MIT prior to Stage II training had no effect on the expression of fear during Stage II and had no effect on fear learning in controls, but prevented associative blocking and so enabled fear learning to CSB. These results show an important role for MIT in predictive fear learning and are discussed with reference to previous findings implicating the midline and posterior intralaminar thalamus in fear learning and fear responding.

  13. A role for midline and intralaminar thalamus in the associative blocking of Pavlovian fear conditioning

    Directory of Open Access Journals (Sweden)

    Auntora eSengupta

    2014-05-01

    Full Text Available Fear learning occurs in response to positive prediction error, when the expected outcome of a conditioning trial exceeds that predicted by the conditioned stimuli present. This role for error in Pavlovian association formation is best exemplified by the phenomenon of associative blocking, whereby prior fear conditioning of conditioned stimulus (CS A is able to prevent learning to CSB when they are conditioned in compound. The midline and intralaminar thalamic nuclei (MIT are well placed to contribute to fear prediction error because they receive extensive projections from the midbrain periaqueductal gray – which has a key role in fear prediction error – and project extensively to prefrontal cortex and amygdala. Here we used an associative blocking design to study the role of MIT in fear learning. In Stage I rats were trained to fear CSA via pairings with shock. In Stage II rats received compound fear conditioning of CSAB paired with shock. On test, rats that received Stage I training expressed less fear to CSB relative to control rats that did not receive this training. Microinjection of bupivacaine into MIT prior to Stage II training had no effect on the expression of fear during Stage II and had no effect on fear learning in controls, but prevented associative blocking and so enabled fear learning to CSB. These results show an important role for MIT in predictive fear learning and are discussed with reference to previous findings implicating the midline and posterior intralaminar thalamus in fear learning and fear responding.

  14. Opioid receptors regulate the extinction of Pavlovian fear conditioning.

    Science.gov (United States)

    McNally, Gavan P; Westbrook, R Frederick

    2003-12-01

    Rats received a single pairing of an auditory conditioned stimulus (CS) with a footshock unconditioned stimulus (US). The fear (freezing) that had accrued to the CS was then extinguished. Injection of naloxone prior to this extinction significantly impaired the development of extinction. This impairment was mediated by opioid receptors in the brain and was not observed when naloxone was injected after extinction training. Finally, an injection of naloxone on test failed to reinstate extinguished responding that had already accrued to the CS. These experiments show that opioid receptors regulate the development, but not the expression, of fear extinction and are discussed with reference to the roles of opioid receptors in US processing, memory, and appetitive motivation.

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

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    Meike Pappens

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

  16. Necessary and sufficient factors in classical conditioning.

    Science.gov (United States)

    Damianopoulos, E N

    1982-01-01

    The issue of necessary and sufficient factors (pairing-contiguity vs. contingency-correlation) in classical (Pavlovian) excitatory conditioning is examined: first, in terms of definitional (logical) and manipulational requirements of "necessary" and "sufficient"; second, in terms of Boolean logic test models indicating experimental and control manipulations in tests of pairing and contingency as necessary and sufficient factors; and, third, by a selective review of reference experiments showing appropriate experimental and control manipulations of pairing and contingency indicated in the Boolean logic test models. Results of examination show pairing-contiguity as the sole necessary and sufficient factor for excitatory conditioning, while contingency-correlation is conceptualized as a modulating factor controlling minimal-maximal effects of pairing-contiguity. Reservations and diagnostic experiments are indicated to assess effects of uncontrolled conditioned stimulus--unconditioned stimulus (--CS--US) probability characteristics (e.g., p (CS--US)/p (--CS--US) in truly random (TR) schedule manipulations). Similar analysis of conditioned inhibition reveals insufficient evidence to support a choice among current alternatives.

  17. Rating data are underrated: validity of US expectancy in human fear conditioning

    NARCIS (Netherlands)

    Y. Boddez; F. Baeyens; L. Luyten; D. Vansteenwegen; D. Hermans; T. Beckers

    2013-01-01

    Background and objectives: Human fear conditioning is widely regarded as one of the prime paradigms for the study of fear and anxiety disorders. We provide an evaluation of a commonly used subjective measure in the human fear conditioning paradigm, namely the US-expectancy measurement. Methods: We a

  18. Modafinil and memory: effects of modafinil on Morris water maze learning and Pavlovian fear conditioning.

    Science.gov (United States)

    Shuman, Tristan; Wood, Suzanne C; Anagnostaras, Stephan G

    2009-04-01

    Modafinil has been shown to promote wakefulness and some studies suggest the drug can improve cognitive function. Because of many similarities, the mechanism of action may be comparable to classical psychostimulants, although the exact mechanisms of modafinil's actions in wakefulness and cognitive enhancement are unknown. The current study aims to further examine the effects of modafinil as a cognitive enhancer on hippocampus-dependent memory in mice. A high dose of modafinil (75 mg/kg ip) given before training improved acquisition on a Morris water maze. When given only before testing, modafinil did not affect water maze performance. We also examined modafinil (0.075 to 75 mg/kg) on Pavlovian fear conditioning. A low dose of pretraining modafinil (0.75 mg/kg) enhanced memory of contextual fear conditioning (tested off-drug 1 week later) whereas a high dose (75 mg/kg) disrupted memory. Pretraining modafinil did not affect cued conditioning at any dose tested, and immediate posttraining modafinil had no effect on either cued or contextual fear. These results suggest that modafinil's effects of memory are more selective than amphetamine or cocaine and specific to hippocampus-dependent memory.

  19. Object-location training elicits an overlapping but temporally distinct transcriptional profile from contextual fear conditioning.

    Science.gov (United States)

    Poplawski, Shane G; Schoch, Hannah; Wimmer, Mathieu E; Hawk, Joshua D; Walsh, Jennifer L; Giese, Karl P; Abel, Ted

    2014-12-01

    Hippocampus-dependent learning is known to induce changes in gene expression, but information on gene expression differences between different learning paradigms that require the hippocampus is limited. The bulk of studies investigating RNA expression after learning use the contextual fear conditioning task, which couples a novel environment with a footshock. Although contextual fear conditioning has been useful in discovering gene targets, gene expression after spatial memory tasks has received less attention. In this study, we used the object-location memory task and studied gene expression at two time points after learning in a high-throughput manner using a microfluidic qPCR approach. We found that expression of the classic immediate-early genes changes after object-location training in a fashion similar to that observed after contextual fear conditioning. However, the temporal dynamics of gene expression are different between the two tasks, with object-location memory producing gene expression changes that last at least 2 hours. Our findings indicate that different training paradigms may give rise to distinct temporal dynamics of gene expression after learning.

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

    Directory of Open Access Journals (Sweden)

    Marco eCostanzi

    2014-08-01

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

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

    Science.gov (United States)

    Chang, Chun-hui; Maren, Stephen

    2009-01-01

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

  2. The contextual brain: implications for fear conditioning, extinction and psychopathology

    Science.gov (United States)

    Maren, Stephen; Phan, K. Luan; Liberzon, Israel

    2016-01-01

    Contexts surround and imbue meaning to events; they are essential for recollecting the past, interpreting the present and anticipating the future. Indeed, the brain’s capacity to contextualize information permits enormous cognitive and behavioural flexibility. Studies of Pavlovian fear conditioning and extinction in rodents and humans suggest that a neural circuit including the hippocampus, amygdala and medial prefrontal cortex is involved in the learning and memory processes that enable context-dependent behaviour. Dysfunction in this network may be involved in several forms of psychopathology, including post-traumatic stress disorder, schizophrenia and substance abuse disorders. PMID:23635870

  3. Pavlovian fear conditioning as a behavioral assay for hippocampus and amygdala function: cautions and caveats.

    Science.gov (United States)

    Maren, Stephen

    2008-10-01

    Pavlovian fear conditioning has become an important model for investigating the neural substrates of learning and memory in rats, mice and humans. The hippocampus and amygdala are widely believed to be essential for fear conditioning to contexts and discrete cues, respectively. Indeed, this parsing of function within the fear circuit has been used to leverage fear conditioning as a behavioral assay of hippocampal and amygdala function, particularly in transgenic mouse models. Recent work, however, blurs the anatomical segregation of cue and context conditioning and challenges the necessity for the hippocampus and amygdala in fear learning. Moreover, nonassociative factors may influence the performance of fear responses under a variety of conditions. Caution must therefore be exercised when using fear conditioning as a behavioral assay for hippocampal- and amygdala-dependent learning.

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  6. Acute and chronic effects of selective serotonin reuptake inhibitor treatment on fear conditioning: implications for underlying fear circuits.

    Science.gov (United States)

    Burghardt, N S; Bauer, E P

    2013-09-01

    Selective serotonin reuptake inhibitors (SSRIs) are widely used for the treatment of a spectrum of anxiety disorders, yet paradoxically they may increase symptoms of anxiety when treatment is first initiated. Despite extensive research over the past 30 years focused on SSRI treatment, the precise mechanisms by which SSRIs exert these opposing acute and chronic effects on anxiety remain unknown. By testing the behavioral effects of SSRI treatment on Pavlovian fear conditioning, a well characterized model of emotional learning, we have the opportunity to identify how SSRIs affect the functioning of specific brain regions, including the amygdala, bed nucleus of the stria terminalis (BNST) and hippocampus. In this review, we first define different stages of learning involved in cued and context fear conditioning and describe the neural circuits underlying these processes. We examine the results of numerous rodent studies investigating how acute SSRI treatment modulates fear learning and relate these effects to the known functions of serotonin in specific brain regions. With these findings, we propose a model by which acute SSRI administration, by altering neural activity in the extended amygdala and hippocampus, enhances both acquisition and expression of cued fear conditioning, but impairs the expression of contextual fear conditioning. Finally, we review the literature examining the effects of chronic SSRI treatment on fear conditioning in rodents and describe how downregulation of N-methyl-d-aspartate (NMDA) receptors in the amygdala and hippocampus may mediate the impairments in fear learning and memory that are reported. While long-term SSRI treatment effectively reduces symptoms of anxiety, their disruptive effects on fear learning should be kept in mind when combining chronic SSRI treatment and learning-based therapies, such as cognitive behavioral therapy.

  7. Physiological Consequences of Repeated Exposures to Conditioned Fear

    Directory of Open Access Journals (Sweden)

    Robert S. Thompson

    2012-05-01

    Full Text Available Activation of the stress response evokes a cascade of physiological reactions that may be detrimental when repeated or chronic, and when triggered after exposure to psychological/emotional stressors. Investigation of the physiological mechanisms responsible for the health damaging effects requires animal paradigms that repeatedly evoke a response to psychological/emotional stressors. To this end, adult male Sprague Dawley rats were repeatedly exposed (2X per day for 20 days to a context that they were conditioned to fear (conditioned fear test, CFT. Repeated exposure to CFT produced body weight loss, adrenal hypertrophy, thymic involution, and basal corticosterone elevation. In vivo biotelemetry measures revealed that CFT evokes sympathetic nervous system driven increases in heart rate (HR, mean arterial pressure (MAP, and core body temperature. Extinction of behavioral (freezing and physiological responses to CFT was prevented using minimal reinstatement footshock. MAP responses to the CFT did not diminish across 20 days of exposure. In contrast, HR and cardiac contractility responses declined by day 15, suggesting a shift toward vascular-dominated MAP (a pre-clinical marker of CV dysfunction. Flattened diurnal rhythms, common to stress-related mood/anxiety disorders, were found for most physiological measures. Thus, repeated CFT produces adaptations indicative of the health damaging effects of psychological/emotional stress.

  8. Classically conditioned postural reflex in cerebellar patients.

    Science.gov (United States)

    Kolb, F P; Lachauer, S; Maschke, M; Timmann, D

    2004-09-01

    The aim of the current study was to compare postural responses to repetitive platform-evoked perturbations in cerebellar patients with those of healthy subjects using a classical conditioning paradigm. The perturbations consisted of tilting of the platform (unconditioned stimulus: US) at random time intervals, preceded by an auditory signal that represented the conditioning stimulus (CS). Physiological reactions were recorded biomechanically by measuring the vertical ground forces, yielding the center of vertical pressure (CVP), and electrophysiologically by EMG measurements of the main muscle groups of both legs. The recording session consisted of a control section with US-alone trials, a testing section with paired stimuli and a brief final section with US-alone trials. Healthy control subjects were divided into those establishing conditioned responses (CR) in all muscles tested (strategy I) and those with CR in the gastrocnemius muscles only (strategy II), suggesting an associative motor-related process is involved. Patients with a diffuse, non-localized disease were almost unable to establish CR. This was also true for a patient with a focal surgical lesion with no CR on the affected side but who, simultaneously, showed an essentially normal CR incidence on the intact side. During US-alone trials healthy controls exhibited a remarkable decay of the UR amplitude due to a non-associative motor-related process such as habituation. The decay was most prominent in the paired trials section. In contrast, patients showed no significant differences in the UR amplitude throughout the entire recording session. Analysis of the CVP supported the electrophysiological findings, showing CR in the controls only. The differences between the responses of control subjects and those of the cerebellar patients imply strongly that the cerebellum is involved critically in controlling associative and non-associative motor-related processes.

  9. Fear-conditioning mechanisms associated with trait vulnerability to anxiety in humans.

    Science.gov (United States)

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

    2011-02-10

    Investigations of fear conditioning in rodents and humans have illuminated the neural mechanisms underlying cued and contextual fear. A critical question is how personality dimensions such as trait anxiety act through these mechanisms to confer vulnerability to anxiety disorders, and whether humans' ability to overcome acquired fears depends on regulatory skills not characterized in animal models. In a neuroimaging study of fear conditioning in humans, we found evidence for two independent dimensions of neurocognitive function associated with trait vulnerability to anxiety. The first entailed increased amygdala responsivity to phasic fear cues. The second involved impoverished ventral prefrontal cortical (vPFC) recruitment to downregulate both cued and contextual fear prior to omission (extinction) of the aversive unconditioned stimulus. These two dimensions may contribute to symptomatology differences across anxiety disorders; the amygdala mechanism affecting the development of phobic fear and the frontal mechanism influencing the maintenance of both specific fears and generalized anxiety.

  10. Striatal dopamine D1 receptor is essential for contextual fear conditioning.

    Science.gov (United States)

    Ikegami, Masaru; Uemura, Takeshi; Kishioka, Ayumi; Sakimura, Kenji; Mishina, Masayoshi

    2014-02-05

    Fear memory is critical for animals to trigger behavioural adaptive responses to potentially threatening stimuli, while too much or inappropriate fear may cause psychiatric problems. Numerous studies have shown that the amygdala, hippocampus and medial prefrontal cortex play important roles in Pavlovian fear conditioning. Recently, we showed that striatal neurons are required for the formation of the auditory fear memory when the unconditioned stimulus is weak. Here, we found that selective ablation of striatal neurons strongly diminished contextual fear conditioning irrespective of the intensity of footshock. Furthermore, contextual fear conditioning was strongly reduced in striatum-specific dopamine D1 receptor knockout mice. On the other hand, striatum-specific dopamine D2 receptor knockout mice showed freezing responses comparable to those of control mice. These results suggest that striatal D1 receptor is essential for contextual fear conditioning.

  11. Role of conceptual knowledge in learning and retention of conditioned fear.

    Science.gov (United States)

    Dunsmoor, Joseph E; Martin, Alex; LaBar, Kevin S

    2012-02-01

    Associating sensory cues with aversive outcomes is a relatively basic process shared across species. Yet higher-order cognitive processes likely contribute to associative fear learning in many circumstances, especially in humans. Here we ask whether fears can be acquired based on conceptual knowledge of object categories, and whether such concept-based fear conditioning leads to enhanced memory representations for conditioned objects. Participants were presented with a heterogeneous collection of images of animals and tools. Objects from one category were reinforced by an electrical shock, whereas the other category was never reinforced. Results confirmed concept-based fear learning through subjective report of shock expectancy, heightened skin conductance responses, and enhanced 24h recognition memory for items from the conditioned category. These results provide novel evidence that conditioned fear can generalize through knowledge of object concepts, and sheds light on the persistent nature of fear memories and category-based fear responses symptomatic of some anxiety disorders.

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

    Science.gov (United States)

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

    2012-06-01

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

  13. Opioid regulation of Pavlovian overshadowing in fear conditioning.

    Science.gov (United States)

    Zelikowsky, Moriel; Fanselow, Michael S

    2010-08-01

    In Pavlovian overshadowing, a stimulus that predicts a biologically important event reduces conditioning to another, equally predictive stimulus. We tested the effects of an opioid antagonist and dopamine agonist on the ability of a salient white noise to overshadow a less salient light. Rats were conditioned to fear a light or a noise-light compound using a mild footshock. Compound-conditioned rats trained under the saline vehicle revealed significant overshadowing of the light by the noise. This overshadowing effect was significantly attenuated in rats trained under the opioid antagonist naltrexone, consistent with an opioid-mediated negative feedback model of conditioning. In line with predictions made by negative feedback-type models, we failed to obtain overshadowing with few trials, suggesting that the processes underlying conditioning during initial trials do not contribute to the opioid-dependent Pavlovian overshadowing obtained in our preparation. Lastly, we compared the involvement of dopamine-mediated and opioid-mediated processes in overshadowing by conditioning rats under the partial dopamine D1 receptor agonist SKF 38393 or the opioid antagonist naltrexone. Both naltrexone and SKF 38393 were found to attenuate overshadowing; however, the behavioral profiles produced by each pharmacological manipulation were distinct. Collectively, these studies demonstrate an important role for both opioid- and dopamine-mediated processes in multiple-trial overshadowing.

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

    Science.gov (United States)

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

    2016-09-01

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

  15. Double dissociation of amygdala and hippocampal contributions to trace and delay fear conditioning.

    Science.gov (United States)

    Raybuck, Jonathan D; Lattal, K Matthew

    2011-01-19

    A key finding in studies of the neurobiology of learning memory is that the amygdala is critically involved in Pavlovian fear conditioning. This is well established in delay-cued and contextual fear conditioning; however, surprisingly little is known of the role of the amygdala in trace conditioning. Trace fear conditioning, in which the CS and US are separated in time by a trace interval, requires the hippocampus and prefrontal cortex. It is possible that recruitment of cortical structures by trace conditioning alters the role of the amygdala compared to delay fear conditioning, where the CS and US overlap. To investigate this, we inactivated the amygdala of male C57BL/6 mice with GABA (A) agonist muscimol prior to 2-pairing trace or delay fear conditioning. Amygdala inactivation produced deficits in contextual and delay conditioning, but had no effect on trace conditioning. As controls, we demonstrate that dorsal hippocampal inactivation produced deficits in trace and contextual, but not delay fear conditioning. Further, pre- and post-training amygdala inactivation disrupted the contextual but the not cued component of trace conditioning, as did muscimol infusion prior to 1- or 4-pairing trace conditioning. These findings demonstrate that insertion of a temporal gap between the CS and US can generate amygdala-independent fear conditioning. We discuss the implications of this surprising finding for current models of the neural circuitry involved in fear conditioning.

  16. Enhancement of acoustic prepulse inhibition by contextual fear conditioning in mice is maintained even after contextual fear extinction.

    Science.gov (United States)

    Ishii, Daisuke; Matsuzawa, Daisuke; Fujita, Yuko; Sutoh, Chihiro; Ohtsuka, Hiroyuki; Matsuda, Shingo; Kanahara, Nobuhisa; Hashimoto, Kenji; Iyo, Masaomi; Shimizu, Eiji

    2010-02-01

    Prepulse inhibition (PPI) of the acoustic startle response is one of the few and major paradigms for investigating sensorimotor gating systems in humans and rodents in a similar fashion. PPI deficits are observed not only in patients with schizophrenia, but also in patients with anxiety disorders. Previous studies have shown that PPI in rats can be enhanced by auditory fear conditioning. In this study, we evaluated the effects of contextual fear conditioning (FC) for six times a day and fear extinction (FE) for seven days on PPI in mice. C57BL/6J mice (male, 8-12 weeks) were divided into three groups; no-FC (control), FC and FC + FE. We measured PPI at the following three time points, (1) baseline before FC, (2) after FC, and (3) after FE. The results showed that PPI was increased after FC. Moreover, the enhanced PPI following FC was observed even after FE with decreased freezing behaviors. These results suggested contextual fear conditioning could enhance acoustic PPI, and that contextual fear extinction could decrease freezing behaviors, but not acoustic PPI.

  17. Effects of Recent Exposure to a Conditioned Stimulus on Extinction of Pavlovian Fear Conditioning

    Science.gov (United States)

    Chan, Wan Yee Macy; Leung, Hiu T.; Westbrook, R. Frederick; McNally, Gavan P.

    2010-01-01

    In six experiments we studied the effects of a single re-exposure to a conditioned stimulus (CS; "retrieval trial") prior to extinction training (extinction-reconsolidation boundary) on the development of and recovery from fear extinction. A single retrieval trial prior to extinction training significantly augmented the renewal and reinstatement…

  18. Olfactory Fear Conditioning Induces Field Potential Potentiation in Rat Olfactory Cortex and Amygdala

    Science.gov (United States)

    Messaoudi, Belkacem; Granjon, Lionel; Mouly, Anne-Marie; Sevelinges, Yannick; Gervais, Remi

    2004-01-01

    The widely used Pavlovian fear-conditioning paradigms used for studying the neurobiology of learning and memory have mainly used auditory cues as conditioned stimuli (CS). The present work assessed the neural network involved in olfactory fear conditioning, using olfactory bulb stimulation-induced field potential signal (EFP) as a marker of…

  19. Eye Movements Index Implicit Memory Expression in Fear Conditioning.

    Science.gov (United States)

    Hopkins, Lauren S; Schultz, Douglas H; Hannula, Deborah E; Helmstetter, Fred J

    2015-01-01

    The role of contingency awareness in simple associative learning experiments with human participants is currently debated. Since prior work suggests that eye movements can index mnemonic processes that occur without awareness, we used eye tracking to better understand the role of awareness in learning aversive Pavlovian conditioning. A complex real-world scene containing four embedded household items was presented to participants while skin conductance, eye movements, and pupil size were recorded. One item embedded in the scene served as the conditional stimulus (CS). One exemplar of that item (e.g. a white pot) was paired with shock 100 percent of the time (CS+) while a second exemplar (e.g. a gray pot) was never paired with shock (CS-). The remaining items were paired with shock on half of the trials. Participants rated their expectation of receiving a shock during each trial, and these expectancy ratings were used to identify when (i.e. on what trial) each participant became aware of the programmed contingencies. Disproportionate viewing of the CS was found both before and after explicit contingency awareness, and patterns of viewing distinguished the CS+ from the CS-. These observations are consistent with "dual process" models of fear conditioning, as they indicate that learning can be expressed in patterns of viewing prior to explicit contingency awareness.

  20. Eye Movements Index Implicit Memory Expression in Fear Conditioning.

    Directory of Open Access Journals (Sweden)

    Lauren S Hopkins

    Full Text Available The role of contingency awareness in simple associative learning experiments with human participants is currently debated. Since prior work suggests that eye movements can index mnemonic processes that occur without awareness, we used eye tracking to better understand the role of awareness in learning aversive Pavlovian conditioning. A complex real-world scene containing four embedded household items was presented to participants while skin conductance, eye movements, and pupil size were recorded. One item embedded in the scene served as the conditional stimulus (CS. One exemplar of that item (e.g. a white pot was paired with shock 100 percent of the time (CS+ while a second exemplar (e.g. a gray pot was never paired with shock (CS-. The remaining items were paired with shock on half of the trials. Participants rated their expectation of receiving a shock during each trial, and these expectancy ratings were used to identify when (i.e. on what trial each participant became aware of the programmed contingencies. Disproportionate viewing of the CS was found both before and after explicit contingency awareness, and patterns of viewing distinguished the CS+ from the CS-. These observations are consistent with "dual process" models of fear conditioning, as they indicate that learning can be expressed in patterns of viewing prior to explicit contingency awareness.

  1. Appetitive and aversive classical conditioning of female sexual response

    NARCIS (Netherlands)

    S. Both; E. Laan; M. Spiering; T. Nilsson; S. Oomens; W. Everaerd

    2008-01-01

    INTRODUCTION: There is only limited evidence for appetitive classical conditioning of female sexual response, and to date modulation of female sexual response by aversive conditioning has not been studied. AIM: The aim of this article is to study appetitive and aversive classical conditioning of sex

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

    Science.gov (United States)

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

    2014-07-01

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

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

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    Maria Anne Briscione

    2014-07-01

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

  4. Blood pressure variations real-time reflect the conditioned fear learning and memory.

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    Yuan-Chang Hsu

    Full Text Available The conditioned fear learning and memory occurs when a neutral conditioned stimulus (CS is paired with an aversive unconditioned stimulus (US. This process is critically dependent on the amygdala and inevitably involves blood pressure (BP alterations. We hypothesized that BP variations could instantaneously reveal individual steps during conditioned fear learning and memory. An implanted telemetric probe was used to monitor the BP real-time in rats during training and testing sessions of the fear-potentiated startle. Our results showed that (i the conditioned fear learning during the training sessions was reflected by light (CS-induced rapid BP elevations and by electric shock (US-evoked sympathetic tone elevations; (ii these two BP-related parameters were not only negatively correlated with each other but also coupled to each other in the training session trials; (iii both parameters closely predicted the performance of fear-potentiated startle on the next day; and (iv although local blocking of one of the two fear-conditioned pathways in the training session partially inhibited fear learning, the fear memory retrieval still used both pathways. Altogether, real-time blood pressure variations faithfully revealed the critical steps involved in conditioned fear learning and memory, and our results supported a coupling between the cued learning and the post-shock calmness.

  5. Conditioned fear associated phenotypes as robust, translational indices of trauma-, stressor-, and anxiety-related behaviors.

    Science.gov (United States)

    Briscione, Maria Anne; Jovanovic, Tanja; Norrholm, Seth Davin

    2014-01-01

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

  6. Imaging learning and memory: classical conditioning.

    Science.gov (United States)

    Schreurs, B G; Alkon, D L

    2001-12-15

    The search for the biological basis of learning and memory has, until recently, been constrained by the limits of technology to classic anatomic and electrophysiologic studies. With the advent of functional imaging, we have begun to delve into what, for many, was a "black box." We review several different types of imaging experiments, including steady state animal experiments that image the functional labeling of fixed tissues, and dynamic human studies based on functional imaging of the intact brain during learning. The data suggest that learning and memory involve a surprising conservation of mechanisms and the integrated networking of a number of structures and processes.

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

    Directory of Open Access Journals (Sweden)

    Nicole eHuff

    2011-11-01

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

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

    Science.gov (United States)

    Wilson, Yvette M.; Murphy, Mark

    2009-01-01

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

  9. Effects of Stress and Sex on Acquisition and Consolidation of Human Fear Conditioning

    Science.gov (United States)

    Kuhn, Cynthia M.; LaBar, Kevin S.; Zorawski, Michael; Blanding, Nineequa Q.

    2006-01-01

    We examined the relationship between stress hormone (cortisol) release and acquisition and consolidation of conditioned fear learning in healthy adults. Participants underwent acquisition of differential fear conditioning, and consolidation was assessed in a 24-h delayed extinction test. The acquisition phase was immediately followed by an 11-min…

  10. The Effect of Counterconditioning on Evaluative Responses and Harm Expectancy in a Fear Conditioning Paradigm

    NARCIS (Netherlands)

    A.K. Raes (Ann); R. de Raedt (Rudi)

    2012-01-01

    textabstractIn fear conditioning, extinction targets harm expectancy as well as the fear response, but it often fails to eradicate the negative affective value that is associated with the conditioned stimulus. In the present study, we examined whether counterconditioning can serve to reduce evaluati

  11. The Writer’s Condition and the Concept of Fear

    Directory of Open Access Journals (Sweden)

    Alina Beatrice Chesca

    2010-07-01

    Full Text Available This paper approaches Otto Rank’s theory according to which the main cause of anxiety is the individual’s separation from the loved beings and objects. Along one’s life, anxiety takes two forms: the fear of life and the fear of death. The fear of life is the anxiety which appears when the person becomes aware of his creative abilities which could separate him from the existing relationships. Writers like Emil Cioran, Mihail Sebastian, Octavian Paler, Yukio Mishima, Ernest Hemingway suffered from the fear of life, they were haunted by a tragic that brought about theloneliness of death. It is what Kierkegaard called: ”the fatal disease”, the sin of the artist’s existence. The artistic process implies an oscillation between acceptance and rejection, satisfaction and negation, life and death, loneliness and happiness.

  12. Systemic blockade of D2-like dopamine receptors facilitates extinction of conditioned fear in mice

    OpenAIRE

    Ponnusamy, Ravikumar; Nissim, Helen A.; Barad, Mark

    2005-01-01

    Extinction of conditioned fear in animals is the explicit model of behavior therapy for human anxiety disorders, including panic disorder, obsessive-compulsive disorder, and post-traumatic stress disorder. Based on previous data indicating that fear extinction in rats is blocked by quinpirole, an agonist of dopamine D2 receptors, we hypothesized that blockade of D2 receptors might facilitate extinction in mice, while agonists should block extinction, as they do in rats. One day after fear con...

  13. Postural responses explored through classical conditioning.

    Science.gov (United States)

    Campbell, A D; Dakin, C J; Carpenter, M G

    2009-12-15

    The purpose of the study was to determine whether the central nervous system (CNS) requires the sensory feedback generated by balance perturbations in order to trigger postural responses (PRs). In Experiment 1, twenty-one participants experienced toes-up support-surface tilts in two blocks. Control blocks involved unexpected balance perturbations whereas an auditory tone cued the onset of balance perturbations in Conditioning blocks. A single Cue-Only trial followed each block (Cue-Only(Control) and Cue-Only(Conditioning) trials) in the absence of balance perturbations. Cue-Only(Conditioning) trials were used to determine whether postural perturbations were required in order to trigger PRs. Counter-balancing the order of Control and Conditioning blocks allowed Cue-Only(Control) trials to examine both the audio-spinal/acoustic startle effects of the auditory cue and the carryover effects of the initial conditioning procedure. In Experiment 2, six participants first experienced five consecutive Tone-Only trials that were followed by twenty-five conditioning trials. After conditioning, five Tone-Only trials were again presented consecutively to first elicit and then extinguish the conditioned PRs. Surface electromyography (EMG) recorded muscle activity in soleus (SOL), tibialis anterior (TA) and rectus femoris (RF). EMG onset latencies and amplitudes were calculated together with the onset latency, peak and time-to-peak of shank angular accelerations. Results indicated that an auditory cue could be conditioned to initiate PRs in multiple muscles without balance-relevant sensory triggers generated by balance perturbations. Postural synergies involving excitation of TA and RF and inhibition of SOL were observed following the Cue-Only(Conditioning) trials that resulted in shank angular accelerations in the direction required to counter the expected toes-up tilt. Postural synergies were triggered in response to the auditory cue even 15 min post-conditioning. Furthermore

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

    Directory of Open Access Journals (Sweden)

    Bernard G Schreurs

    2015-04-01

    Full Text Available Not everyone exposed to trauma suffers flashbacks, bad dreams, numbing, fear, anxiety, sleeplessness, hyper-vigilance, hyperarousal, or an inability to cope, but those who do may suffer from post traumatic stress disorder (PTSD. PTSD is a major physical and mental health problem for military personnel and civilians exposed to trauma. There is still debate about the incidence and prevalence of PTSD especially among the military, but for those who are diagnosed, behavioral therapy and drug treatment strategies have proven to be less than effective. A number of these treatment strategies are based on rodent fear conditioning research and are capable of treating only some of the symptoms because the extinction of fear does not deal with the various forms of hyper-vigilance and hyperarousal experienced by people with PTSD. To help address this problem, we have developed a preclinical eyeblink classical conditioning model of PTSD in which conditioning and hyperarousal can both be extinguished. We review this model and discuss findings showing that unpaired stimulus presentations can be effective in reducing levels of conditioning and hyperarousal even when unconditioned stimulus intensity is reduced to the point where it is barely capable of eliciting a response. These procedures have direct implications for the treatment of PTSD and could be implemented in a virtual reality environment.

  15. Eyeblink classical conditioning and post-traumatic stress disorder - a model systems approach.

    Science.gov (United States)

    Schreurs, Bernard G; Burhans, Lauren B

    2015-01-01

    Not everyone exposed to trauma suffers flashbacks, bad dreams, numbing, fear, anxiety, sleeplessness, hyper-vigilance, hyperarousal, or an inability to cope, but those who do may suffer from post-traumatic stress disorder (PTSD). PTSD is a major physical and mental health problem for military personnel and civilians exposed to trauma. There is still debate about the incidence and prevalence of PTSD especially among the military, but for those who are diagnosed, behavioral therapy and drug treatment strategies have proven to be less than effective. A number of these treatment strategies are based on rodent fear conditioning research and are capable of treating only some of the symptoms because the extinction of fear does not deal with the various forms of hyper-vigilance and hyperarousal experienced by people with PTSD. To help address this problem, we have developed a preclinical eyeblink classical conditioning model of PTSD in which conditioning and hyperarousal can both be extinguished. We review this model and discuss findings showing that unpaired stimulus presentations can be effective in reducing levels of conditioning and hyperarousal even when unconditioned stimulus intensity is reduced to the point where it is barely capable of eliciting a response. These procedures have direct implications for the treatment of PTSD and could be implemented in a virtual reality environment.

  16. Learning and memory in conditioned fear extinction: effects of d-cycloserine

    NARCIS (Netherlands)

    B. Vervliet

    2008-01-01

    This review addresses the effects of the cognitive enhancer D-cycloserine (DCS) on the memory processes that occur in conditioned fear extinction, which is the experimental model for exposure techniques to reduce clinical anxiety. All reported rat studies show an enhanced fear extinction effect when

  17. Factors Regulating the Effects of Hippocampal Inactivation on Renewal of Conditional Fear after Extinction

    Science.gov (United States)

    Corcoran, Kevin A.; Maren, Stephen

    2004-01-01

    After extinction of fear to a Pavlovian conditional stimulus (CS), contextual stimuli come to regulate the expression of fear to that CS. There is growing evidence that the context dependence of memory retrieval after extinction involves the hippocampus. In the present experiment, we examine whether hippocampal involvement in memory retrieval…

  18. Electrolytic Lesions of the Dorsal Hippocampus Disrupt Renewal of Conditional Fear after Extinction

    Science.gov (United States)

    Ji, Jinzhao; Maren, Stephen

    2005-01-01

    There is a growing body of evidence that the hippocampus is critical for context-dependent memory retrieval. In the present study, we used Pavlovian fear conditioning in rats to examine the role of the dorsal hippocampus (DH) in the context-specific expression of fear memory after extinction (i.e., renewal). Pre-training electrolytic lesions of…

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

    Directory of Open Access Journals (Sweden)

    Thomas Francis Giustino

    2015-11-01

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

  20. Exposure to Novelty Weakens Conditioned Fear in Long-Evans Rats

    Science.gov (United States)

    Anderson, Matthew J.; Burpee, Tara E.; Wall, Matthew J.; McGraw, Justin J.

    2013-01-01

    The present study sought to determine whether post-training exposure to a novel or familiar object, encountered in either the location of the original fear conditioning (black compartment of a passive avoidance {PA} chamber) or in a neutral setting (open field where initial object training had occurred) would prove capable of reducing fear at…

  1. Blushing-Fearful Individuals' Judgmental Biases and Conditional Cognitions : An Internet Inquiry

    NARCIS (Netherlands)

    Dijk, Corine; de Jong, Peter J.; Muller, Elke; Boersma, Wietse

    2010-01-01

    The present study examines two mechanisms that might explain why blushing-fearful individuals fear blushing: Judgmental biases for blushing in ordinary social situations that usually do not elicit a blush, and negative conditional cognitions about blushing irrespective of situation. A web-based self

  2. Blushing-fearful individuals’ judgmental biases and conditional cognitions: an internet inquiry

    NARCIS (Netherlands)

    Dijk, C.; de Jong, P.J.; Müller, E.; Boersma, W.

    2010-01-01

    The present study examines two mechanisms that might explain why blushing-fearful individuals fear blushing: Judgmental biases for blushing in ordinary social situations that usually do not elicit a blush, and negative conditional cognitions about blushing irrespective of situation. A web-based self

  3. A Neuronal Model of Classical Conditioning.

    Science.gov (United States)

    1987-10-01

    cell firing. Evidence of conditioning was obtained in the form of enhanced EPSPs , with the enhancement being sustained for up to 41 minutes. The...test- EPSPs . Expericiental brain Research, 4i, 124-134. Barron, R. L. (1968). Self-organizing and kdrning control systei,,s. In 11. L. Ustreicher & D

  4. Cerebellar Secretin Modulates Eyeblink Classical Conditioning

    Science.gov (United States)

    Fuchs, Jason R.; Robinson, Gain M.; Dean, Aaron M.; Schoenberg, Heidi E.; Williams, Michael R.; Morielli, Anthony D.; Green, John T.

    2014-01-01

    We have previously shown that intracerebellar infusion of the neuropeptide secretin enhances the acquisition phase of eyeblink conditioning (EBC). Here, we sought to test whether endogenous secretin also regulates EBC and to test whether the effect of exogenous and endogenous secretin is specific to acquisition. In Experiment 1, rats received…

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

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    Sabiha K Barot

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

  6. Metabotropic glutamate subtype 5 receptors modulate fear-conditioning induced enhancement of prepulse inhibition in rats.

    Science.gov (United States)

    Zou, Dan; Huang, Juan; Wu, Xihong; Li, Liang

    2007-02-01

    Non-startling acoustic events presented shortly before an intense startling sound can inhibit the acoustic startle reflex. This phenomenon is called prepulse inhibition (PPI), and is widely used as a model of sensorimotor gating. The present study investigated whether PPI can be modulated by fear conditioning, whose acquisition can be blocked by the specific antagonist of metabotropic glutamate receptors subtype 5 (mGluR5), 2-methyl-6-(phenylethynyl)-pyridine (MPEP). The results show that a gap embedded in otherwise continuous noise sounds, which were delivered by two spatially separated loudspeakers, could inhibit the startle reflex induced by an intense sound that was presented 50 ms after the gap. The inhibitory effect depended on the duration of the gap, and was enhanced by fear conditioning that was introduced by temporally pairing the gap with footshock. Intraperitoneal injection of MPEP (0.5 or 5mg/kg) 30 min before fear conditioning blocked the enhancing effect of fear conditioning on PPI, but did not affect either the baseline startle magnitude or PPI if no fear conditioning was introduced. These results indicate that PPI is enhanced when the prepulse signifies an aversive event after fear conditioning. Also, mGlu5Rs play a role in preserving the fear-conditioning-induced enhancement of PPI.

  7. Cerebellar cortical inhibition and classical eyeblink conditioning.

    Science.gov (United States)

    Bao, Shaowen; Chen, Lu; Kim, Jeansok J; Thompson, Richard F

    2002-02-01

    The cerebellum is considered a brain structure in which memories for learned motor responses (e.g., conditioned eyeblink responses) are stored. Within the cerebellum, however, the relative importance of the cortex and the deep nuclei in motor learning/memory is not entirely clear. In this study, we show that the cerebellar cortex exerts both basal and stimulus-activated inhibition to the deep nuclei. Sequential application of a gamma-aminobutyric acid type A receptor (GABA(A)R) agonist and a noncompetitive GABA(A)R antagonist allows selective blockade of stimulus-activated inhibition. By using the same sequential agonist and antagonist methods in behaving animals, we demonstrate that the conditioned response (CR) expression and timing are completely dissociable and involve different inhibitory inputs; although the basal inhibition modulates CR expression, the conditioned stimulus-activated inhibition is required for the proper timing of the CR. In addition, complete blockade of cerebellar deep nuclear GABA(A)Rs prevents CR acquisition. Together, these results suggest that different aspects of the memories for eyeblink CRs are encoded in the cerebellar cortex and the cerebellar deep nuclei.

  8. Slow late component in conditioned stimulus-evoked potentials from the amygdala after fear conditioning in the rat

    NARCIS (Netherlands)

    Knippenberg, J.M.J.; Luijtelaar, E.L.J.M. van; Maes, J.H.R.

    2003-01-01

    Male Wistar rats were subjected to a differential Pavlovian fear conditioning procedure in which one of two tones (6 or 10 kHz) was followed by an electric shock (CS+) and the other was not (CS-). Before and after fear cnditioning, we recorded the evoked potentials elicited by CS+ and CS- from elect

  9. Temporary inhibition of dorsal or ventral hippocampus by muscimol: distinct effects on measures of innate anxiety on the elevated plus maze, but similar disruption of contextual fear conditioning.

    Science.gov (United States)

    Zhang, Wei-Ning; Bast, Tobias; Xu, Yan; Feldon, Joram

    2014-04-01

    Studies in rats, involving hippocampal lesions and hippocampal drug infusions, have implicated the hippocampus in the modulation of anxiety-related behaviors and conditioned fear. The ventral hippocampus is considered to be more important for anxiety- and fear-related behaviors than the dorsal hippocampus. In the present study, we compared the role of dorsal and ventral hippocampus in innate anxiety and classical fear conditioning in Wistar rats, examining the effects of temporary pharmacological inhibition by the GABA-A agonist muscimol (0.5 ug/0.5 ul/side) in the elevated plus maze and on fear conditioning to a tone and the conditioning context. In the elevated plus maze, dorsal and ventral hippocampal muscimol caused distinct behavioral changes. The effects of ventral hippocampal muscimol were consistent with suppression of locomotion, possibly accompanied by anxiolytic effects, whereas the pattern of changes caused by dorsal hippocampal muscimol was consistent with anxiogenic effects. In contrast, dorsal and ventral hippocampal muscimol caused similar effects in the fear conditioning experiments, disrupting contextual, but not tone, fear conditioning.

  10. Social fear conditioning as an animal model of social anxiety disorder.

    Science.gov (United States)

    Toth, Iulia; Neumann, Inga D; Slattery, David A

    2013-01-01

    Social fear and avoidance of social situations represent the main behavioral symptoms of social anxiety disorder (SAD), a disorder that is poorly elucidated and has rather unsatisfactory therapeutic options. Therefore, animal models are needed to study the underlying etiology of the disorder and possible novel treatment approaches. However, the current paradigms modeling SAD-like symptoms in rodents are not specific, as they induce numerous other behavioral deficits in addition to social fear and avoidance. Here, we describe the protocol for the social fear conditioning paradigm, an animal model of SAD that specifically induces social fear of unfamiliar con-specifics without potentially confounding alterations in other behavioral measures. Theoretical and practical considerations for performing the social fear conditioning paradigm in both rats and mice, as well as for the analysis and interpretation of the obtained data, are described in detail.

  11. An organization of visual and auditory fear conditioning in the lateral amygdala.

    Science.gov (United States)

    Bergstrom, Hadley C; Johnson, Luke R

    2014-12-01

    Pavlovian fear conditioning is an evolutionary conserved and extensively studied form of associative learning and memory. In mammals, the lateral amygdala (LA) is an essential locus for Pavlovian fear learning and memory. Despite significant progress unraveling the cellular mechanisms responsible for fear conditioning, very little is known about the anatomical organization of neurons encoding fear conditioning in the LA. One key question is how fear conditioning to different sensory stimuli is organized in LA neuronal ensembles. Here we show that Pavlovian fear conditioning, formed through either the auditory or visual sensory modality, activates a similar density of LA neurons expressing a learning-induced phosphorylated extracellular signal-regulated kinase (p-ERK1/2). While the size of the neuron population specific to either memory was similar, the anatomical distribution differed. Several discrete sites in the LA contained a small but significant number of p-ERK1/2-expressing neurons specific to either sensory modality. The sites were anatomically localized to different levels of the longitudinal plane and were independent of both memory strength and the relative size of the activated neuronal population, suggesting some portion of the memory trace for auditory and visually cued fear conditioning is allocated differently in the LA. Presenting the visual stimulus by itself did not activate the same p-ERK1/2 neuron density or pattern, confirming the novelty of light alone cannot account for the specific pattern of activated neurons after visual fear conditioning. Together, these findings reveal an anatomical distribution of visual and auditory fear conditioning at the level of neuronal ensembles in the LA.

  12. Acute withdrawal from repeated cocaine treatment enhances latent inhibition of a conditioned fear response.

    Science.gov (United States)

    Murphy, C A; Heidbreder, C; Feldon, J

    2001-02-01

    Psychostimulant-induced locomotor sensitization and disrupted latent inhibition (LI) of a classically conditioned association are two paradigms that have been widely studied as animal behavioural models of psychosis. In this study we assessed the effects of withdrawal from the repeated intermittent administration of cocaine on LI of a conditioned fear response. Animals which were either preexposed (PE) to a tone conditioned stimulus (CS) or naive to the tone (i.e. non-preexposed: NPE) subsequently experienced 10 pairings of the tone CS with footshock. Afterwards, both groups received five daily injections of cocaine (20 mg/kg, i.p.) or saline. After 3 days of withdrawal from drug treatment, animals were tested for conditioned freezing to the context of the footshock chamber, and 1 day later, for conditioned freezing to the tone CS. Cocaine-sensitized animals exhibited markedly enhanced LI compared to saline-treated animals, due to the fact that NPE-cocaine animals spent more time freezing during the tone CS than NPE-saline animals, whereas PE-cocaine animals showed a tendency toward reduced freezing compared to the saline groups. While these results suggest the presence of increased anxiety in cocaine-withdrawn NPE animals, the absence of this effect in cocaine-withdrawn PE rats indicates that cocaine withdrawal also influences the retrieval of previously learned information.

  13. PKMzeta maintains spatial, instrumental, and classically conditioned long-term memories.

    Directory of Open Access Journals (Sweden)

    Peter Serrano

    2008-12-01

    Full Text Available How long-term memories are stored is a fundamental question in neuroscience. The first molecular mechanism for long-term memory storage in the brain was recently identified as the persistent action of protein kinase Mzeta (PKMzeta, an autonomously active atypical protein kinase C (PKC isoform critical for the maintenance of long-term potentiation (LTP. PKMzeta maintains aversively conditioned associations, but what general form of information the kinase encodes in the brain is unknown. We first confirmed the specificity of the action of zeta inhibitory peptide (ZIP by disrupting long-term memory for active place avoidance with chelerythrine, a second inhibitor of PKMzeta activity. We then examined, using ZIP, the effect of PKMzeta inhibition in dorsal hippocampus (DH and basolateral amygdala (BLA on retention of 1-d-old information acquired in the radial arm maze, water maze, inhibitory avoidance, and contextual and cued fear conditioning paradigms. In the DH, PKMzeta inhibition selectively disrupted retention of information for spatial reference, but not spatial working memory in the radial arm maze, and precise, but not coarse spatial information in the water maze. Thus retention of accurate spatial, but not procedural and contextual information required PKMzeta activity. Similarly, PKMzeta inhibition in the hippocampus did not affect contextual information after fear conditioning. In contrast, PKMzeta inhibition in the BLA impaired retention of classical conditioned stimulus-unconditioned stimulus (CS-US associations for both contextual and auditory fear, as well as instrumentally conditioned inhibitory avoidance. PKMzeta inhibition had no effect on postshock freezing, indicating fear expression mediated by the BLA remained intact. Thus, persistent PKMzeta activity is a general mechanism for both appetitively and aversively motivated retention of specific, accurate learned information, but is not required for processing contextual, imprecise

  14. Amygdala upregulation of NCAM polysialylation induced by auditory fear conditioning is not required for memory formation, but plays a role in fear extinction.

    Science.gov (United States)

    Markram, Kamila; Lopez Fernandez, Miguel Angel; Abrous, Djoher Nora; Sandi, Carmen

    2007-05-01

    There is much interest to understand the mechanisms leading to the establishment, maintenance, and extinction of fear memories. The amygdala has been critically involved in the processing of fear memories and a number of molecular changes have been implicated in this brain region in relation to fear learning. Although neural cell adhesion molecules (NCAMs) have been hypothesized to play a role, information available about their contribution to fear memories is scarce. We investigate here whether polysialylated NCAM (PSA-NCAM) contributes to auditory fear conditioning in the amygdala. First, PSA-NCAM expression was evaluated in different amygdala nuclei after auditory fear conditioning at two different shock intensities. Results showed that PSA-NCAM expression was increased 24 h post-training only in animals subjected to the highest shock intensity (1mA). Second, PSA-NCAM was cleaved in the basolateral amygdaloid complex through micro-infusions of the enzyme endoneuraminidase N, and the consequences of such treatment were investigated on the acquisition, consolidation, remote memory expression, and extinction of conditioned fear memories. Intra-amygdaloid cleavage of PSA-NCAM did not affect acquisition, consolidation or expression of remote fear memories. However, intra-amygdaloid PSA-NCAM cleavage enhanced fear extinction processes. These results suggest that upregulation of PSA-NCAM is a correlate of fear conditioning that is not necessary for the establishment of fear memory in the amygdala, but participates in mechanisms precluding fear extinction. These findings point out PSA-NCAM as a potential target for the treatment of psychopathologies that involve impairment in fear extinction.

  15. Making Classical Conditioning Understandable through a Demonstration Technique.

    Science.gov (United States)

    Gibb, Gerald D.

    1983-01-01

    One lemon, an assortment of other fruits and vegetables, a tennis ball, and a Galvanic Skin Response meter are needed to implement this approach to teaching about classical conditioning in introductory psychology courses. (RM)

  16. Conditions of the Classical Transmission Line Equations at High Frequency

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    New transmission line equations are deduced applying Maxwell's equations in this paper. The conditions of the classical transmission line equations have been discussed, which is important to solve the EM problems in high frequency case.

  17. Identification of plasticity-associated genes regulated by Pavlovian fear conditioning in the lateral amygdala.

    Science.gov (United States)

    Ploski, Jonathan E; Park, Kevin W; Ping, Junli; Monsey, Melissa S; Schafe, Glenn E

    2010-02-01

    Most recent studies aimed at defining the cellular and molecular mechanisms of Pavlovian fear conditioning have focused on protein kinase signaling pathways and the transcription factor cAMP-response element binding protein (CREB) that promote fear memory consolidation in the lateral nucleus of the amygdala (LA). Despite this progress, there still remains a paucity of information regarding the genes downstream of CREB that are required for long-term fear memory formation in the LA. We have adopted a strategy of using microarray technology to initially identify genes induced within the dentate gyrus following in vivo long-term potentiation (LTP) followed by analysis of whether these same genes are also regulated by fear conditioning within the LA. In the present study, we first identified 34 plasticity-associated genes that are induced within 30 min following LTP induction utilizing a combination of DNA microarray, qRT-PCR, and in situ hybridization. To determine whether these genes are also induced in the LA following Pavlovian fear conditioning, we next exposed rats to an auditory fear conditioning protocol or to control conditions that do not support fear learning followed by qRT-PCR on mRNA from microdissected LA samples. Finally, we asked whether identified genes induced by fear learning in the LA are downstream of the extracellular-regulated kinase/mitogen-activated protein kinase signaling cascade. Collectively, our findings reveal a comprehensive list of genes that represent the first wave of transcription following both LTP induction and fear conditioning that largely belong to a class of genes referred to as 'neuronal activity dependent genes' that are likely calcium, extracellular-regulated kinase/mitogen-activated protein kinase, and CREB-dependent.

  18. Classical-Conditioning Demonstrations for Elementary and Advanced Courses.

    Science.gov (United States)

    Abramson, Charles I.; And Others

    1996-01-01

    Describes two new exercises in classical conditioning that use earthworms and houseflies. The animals are available year-round and pose no risk to the students or instructor. The conditioned stimuli are odorants. These elicit a conditioned response of contraction in worms or proboscis extension in flies. (MJP)

  19. Auditory Cortex is Important in the Extinction of Two Different Tone-Based Conditioned Fear Memories in Rats

    OpenAIRE

    Eun Young Song; Boatman, Jeffrey A; Jung, Min W.; Kim, Jeansok J.

    2010-01-01

    Extensive fear extinction research is guided by the view that there are structures in the brain that develop inhibitory control over the expression of conditioned fear memories. While the medial prefrontal cortex has recently captured attention as the locus of plasticity essential for extinction of conditioned fear, the auditory cortex is another plausible cortical area involved in extinction learning since it is considered a sufficient conditioned stimulus (CS) pathway in tone fear conditio...

  20. Fear conditioning enhances γ oscillations and their entrainment of neurons representing the conditioned stimulus.

    Science.gov (United States)

    Headley, Drew B; Weinberger, Norman M

    2013-03-27

    Learning alters the responses of neurons in the neocortex, typically strengthening their encoding of behaviorally relevant stimuli. These enhancements are studied extensively in the auditory cortex by characterizing changes in firing rates and evoked potentials. However, synchronous activity is also important for the processing of stimuli, especially the relationship between gamma oscillations in the local field potential and spiking. We investigated whether tone/shock fear conditioning in rats, a task known to alter responses in auditory cortex, also modified the relationship between gamma and unit activity. A boost in gamma oscillations developed, especially at sites tuned near the tone, and strengthened across multiple conditioning sessions. Unit activity became increasingly phase-locked to gamma, with sites tuned near the tone developing enhanced phase-locking during the tone, whereas those tuned away maintained a tendency to decrease their phase-locking. Enhancements in the coordination of spiking between sites tuned near the tone developed within the first conditioning session and remained throughout the rest of training. Enhanced cross-covariances in unit activity were strongest for subjects that exhibited robust conditioned fear. These results illustrate that changes in sensory cortex during associative learning extend to the coordination of neurons encoding the relevant stimulus, with implications for how it is processed downstream.

  1. Fear Conditioning Effects on Sensitivity to Drug Reward

    Science.gov (United States)

    2010-06-01

    interference. Behav Neural Biol 1989;51:108-13. Kamprath K, Marsicano G, Tang J, Monory K, Bisogno T, Di Marzo V, et al. Cannabinoid CB1 receptor mediates...RD, Pandolfo P, Takahashi RN. The cannabinoid receptor agonist WIN 55,212-2 facilitates the extinction of contextual fear memory and spatial memory...Kaplan GB, Leite-Morris KA, Klufas MA, Fan W (2009). Intra-VTA adenosine A1 receptor activation blocks morphine stimulation of motor behavior and

  2. Social fear conditioning: a novel and specific animal model to study social anxiety disorder.

    Science.gov (United States)

    Toth, Iulia; Neumann, Inga D; Slattery, David A

    2012-05-01

    Social anxiety disorder (SAD) is a major health concern with high lifetime prevalence. The current medication is rather unspecific and, despite considerable efforts, its efficacy is still unsatisfactory. However, there are no appropriate and specific animal models available to study the underlying etiology of the disorder. Therefore, we aimed to establish a model of specific social fear in mice and use this social fear conditioning (SFC) model to assess the therapeutic efficacy of the benzodiazepine diazepam and of the antidepressant paroxetine; treatments currently used for SAD patients. We show that by administering electric foot shocks (2-5, 1 s, 0.7 mA) during the investigation of a con-specific, the investigation of unfamiliar con-specifics was reduced for both the short- and long-term, indicating lasting social fear. The induced fear was specific to social stimuli and did not lead to other behavioral alterations, such as fear of novelty, general anxiety, depression, and impaired locomotion. We show that social fear was dose-dependently reversed by acute diazepam, at doses that were not anxiolytic in a non-social context, such as the elevated plus maze. Finally, we show that chronic paroxetine treatment reversed social fear. All in all, we demonstrated robust social fear after exposure to SFC in mice, which was reversed with both acute benzodiazepine and chronic antidepressant treatment. We propose the SFC model as an appropriate animal model to identify the underlying etiology of SAD and possible novel treatment approaches.

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

    Directory of Open Access Journals (Sweden)

    Candace M. Raio

    2015-01-01

    Full Text Available Fear learning and regulation is a prominent model for describing the pathogenesis of anxiety disorders and stress-related psychopathology. Fear expression can be modulated using a number of regulatory strategies, including extinction, cognitive emotion regulation, avoidance strategies and reconsolidation. In this review, we examine research investigating the effects of acute stress and stress hormones on these regulatory techniques. We focus on what is known about the impact of stress on the ability to flexibly regulate fear responses that are acquired through Pavlovian fear conditioning. Our primary aim is to explore the impact of stress on fear regulation in humans. Given this, we focus on techniques where stress has been linked to alterations of fear regulation in humans (extinction and emotion regulation, and briefly discuss other techniques (avoidance and reconsolidation where the impact of stress or stress hormones have been mainly explored in animal models. These investigations reveal that acute stress may impair the persistent inhibition of fear, presumably by altering prefrontal cortex function. Characterizing the effects of stress on fear regulation is critical for understanding the boundaries within which existing regulation strategies are viable in everyday life and can better inform treatment options for those who suffer from anxiety and stress-related psychopathology.

  4. Effects of stress and sex on acquisition and consolidation of human fear conditioning

    OpenAIRE

    Zorawski, Michael; Blanding, Nineequa Q.; Kuhn, Cynthia M.; LaBar, Kevin S.

    2006-01-01

    We examined the relationship between stress hormone (cortisol) release and acquisition and consolidation of conditioned fear learning in healthy adults. Participants underwent acquisition of differential fear conditioning, and consolidation was assessed in a 24-h delayed extinction test. The acquisition phase was immediately followed by an 11-min psychosocial stress period (arithmetic test combined with a public speech). Salivary cortisol was sampled at various time points before and after ac...

  5. A novel form of memory for auditory fear conditioning at a low-intensity unconditioned stimulus.

    Directory of Open Access Journals (Sweden)

    Ayumi Kishioka

    Full Text Available Fear is one of the most potent emotional experiences and is an adaptive component of response to potentially threatening stimuli. On the other hand, too much or inappropriate fear accounts for many common psychiatric problems. Cumulative evidence suggests that the amygdala plays a central role in the acquisition, storage and expression of fear memory. Here, we developed an inducible striatal neuron ablation system in transgenic mice. The ablation of striatal neurons in the adult brain hardly affected the auditory fear learning under the standard condition in agreement with previous studies. When conditioned with a low-intensity unconditioned stimulus, however, the formation of long-term fear memory but not short-tem memory was impaired in striatal neuron-ablated mice. Consistently, the ablation of striatal neurons 24 h after conditioning with the low-intensity unconditioned stimulus, when the long-term fear memory was formed, diminished the retention of the long-term memory. Our results reveal a novel form of the auditory fear memory depending on striatal neurons at the low-intensity unconditioned stimulus.

  6. Interplay between serotonin and cannabinoid function in the amygdala in fear conditioning.

    Science.gov (United States)

    Nasehi, Mohammad; Davoudi, Kamelia; Ebrahimi-Ghiri, Mohaddeseh; Zarrindast, Mohammad-Reza

    2016-04-01

    The possible interactions between the cannabinoid and serotonin systems in the regions of the brain involved in emotional learning and memory formation have been studied by some researchers. In view of the key role of the amygdala in the acquisition and expression of fear memory, we investigated the involvement of basolateral amygdala (BLA) serotonin 5-HT4 receptors in arachidonylcyclopropylamide (ACPA; selective CB1 cannabinoid receptor agonist)-induced fear memory consolidation impairment. In our study, a context and tone fear conditioning apparatus was used for testing fear conditioning in adult male NMRI mice. The results showed that intraperitoneal administration of ACPA 0.5 or 0.05, 0.1 and 0.5mg/kg immediately after training decreased the percentage of freezing time in context or tone fear conditioning respectively, suggesting a context- or tone-dependent fear memory consolidation impairment. Post-training intra-BLA microinjections of RS67333, as 5-HT4 serotonin receptor agonist, at doses of 0.025 and 0.05 µg/mouse also impaired context or tone memory consolidation, while RS23597, as 5-HT4 serotonin receptor antagonist, did not produce a marked difference in both fear memories as compared with the control group. Moreover, a subthreshold dose of RS67333 did not alter ACPA response in both fear conditionings. Interestingly, a subthreshold dose of RS23597 potentiated or reversed ACPA response at the dose of 0.01 or 0.05 respectively. It is concluded that BLA serotonin 5-HT4 receptors are involved in tone-dependent fear memory consolidation impairment induced by CB1 activation using ACPA, suggesting a modulatory role for serotonin 5-HT4 receptor.

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

    Science.gov (United States)

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

    2013-07-01

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

  8. S6-4: Visual Awareness Modulated by Conditioned Fear during Bistable Perception

    Directory of Open Access Journals (Sweden)

    Chai-Youn Kim

    2012-10-01

    Full Text Available Bistable perception has been considered as a useful means to study visual awareness since it induces spontaneous fluctuation in awareness despite constant physical stimulation. Whether visual awareness during bistable perception is modulated by emotional valence associated with one of the two visual interpretations has been of great interest. This talk will present results from a couple of recent studies in my lab to investigate this issue. By comparing bistable perception prior to and followed by Pavlovian fear conditioning using disambiguated versions of the ambiguous figure, I and my colleagues found that negative emotional valence associated with one of two interpretations significantly influences conscious visual awareness during bistable perception. Specifically after fear conditioning, participants tended to be consciously aware of the interpretation associated with the aversive stimulation (CS+ longer at a time compared to the other (CS-. This influence of fear conditioning on bistable perception occurs only when the fear conditioning was effective indicated by the participant's differential physiological response (heart rate to CS+ and CS-. Changes in bistable perception after fear conditioning were also found to be correlated positively with the State-Anxiety score. I will also discuss results from the follow-up study showing that visual awareness during bistable perception is also modulated “unconsciously” conditioned fear.

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

    Science.gov (United States)

    Bradfield, Laura A.; McNally, Gavan P.

    2010-01-01

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

  10. Acute Cognitive Impairment After Lateral Fluid Percussion Brain Injury Recovers by One Month: Evaluation by Conditioned Fear Response

    OpenAIRE

    2006-01-01

    Conditioned fear associates a contextual environment and cue stimulus to a foot shock in a single training trial, where fear expressed to the trained context or cue indicates cognitive performance. Lesion, aspiration or inactivation of the hippocampus and amygdala impair conditioned fear to the trained context and cue, respectively. Moreover, only bilateral experimental manipulations, in contrast to unilateral, abolish cognitive performance.

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

    Science.gov (United States)

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

    2013-11-01

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

  12. Unconditioned stimulus revaluation to promote conditioned fear extinction in the memory reconsolidation window.

    Directory of Open Access Journals (Sweden)

    Xiang-Xing Zeng

    Full Text Available The retrieval-extinction paradigm, which disrupts the reconsolidation of fear memories in humans, is a non-invasive technique that can be used to prevent the return of fear in humans. In the present study, unconditioned stimulus revaluation was applied in the retrieval-extinction paradigm to investigate its promotion of conditioned fear extinction in the memory reconsolidation window after participants acquired conditioned fear. This experiment comprised three stages (acquisition, unconditioned stimulus revaluation, retrieval-extinction and three methods for indexing fear (unconditioned stimulus expectancy, skin conductance response, conditioned stimulus pleasure rating. After the acquisition phase, we decreased the intensity of the unconditioned stimulus in one group (devaluation and maintained constant for the other group (control. The results indicated that both groups exhibited similar levels of unconditioned stimulus expectancy, but the devaluation group had significantly smaller skin conductance responses and exhibited a growth in conditioned stimulus + pleasure. Thus, our findings indicate unconditioned stimulus revaluation effectively promoted the extinction of conditioned fear within the memory reconsolidation window.

  13. Plasticity of inhibitory synaptic network interactions in the lateral amygdala upon fear conditioning in mice.

    Science.gov (United States)

    Szinyei, Csaba; Narayanan, Rajeevan T; Pape, Hans-Christian

    2007-02-01

    After fear conditioning, plastic changes of excitatory synaptic transmission occur in the amygdala. Fear-related memory also involves the GABAergic system, although no influence on inhibitory synaptic transmission is known. In the present study we assessed the influence of Pavlovian fear conditioning on the plasticity of GABAergic synaptic interactions in the lateral amygdala (LA) in brain slices prepared from fear-conditioned, pseudo-trained and naïve adult mice. Theta-burst tetanization of thalamic afferent inputs to the LA evoked an input-specific potentiation of inhibitory postsynaptic responses in projection neurons; the cortical input was unaffected. Philanthotoxin (10 microM), an antagonist of Ca2+-permeable AMPA receptors, disabled this plastic phenomenon. Surgical isolation of the LA, extracellular application of a GABA(B) receptor antagonist (CGP 55845A, 10 microM) or an NMDA receptor antagonist (APV, 50 microM), or intracellular application of BAPTA (10 mM), did not influence the plasticity. The plasticity also showed as a potentiation of monosynaptic excitatory responses in putative GABAergic interneurons. Pavlovian fear conditioning, but not pseudo-conditioning, resulted in a significant reduction in this potentiation that was evident 24 h after training. Two weeks after training, the potentiation returned to control levels. In conclusion, a reduction in potentiation of inhibitory synaptic interactions occurs in the LA and may contribute to a shift in synaptic balance towards excitatory signal flow during the processes of fear-memory acquisition or consolidation.

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

    Directory of Open Access Journals (Sweden)

    Martínez Karen G

    2012-09-01

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

  15. EXPATRIATES’ MULTIPLE FEARS, FROM TERRORISM TO WORKING CONDITIONS – DEVELOPMENT OF A MODEL

    Directory of Open Access Journals (Sweden)

    Gabriele Giorgi

    2016-10-01

    Full Text Available Companies’ internationalization appears to be fundamental in the current globalized and competitive environment and seems important not only for organizational success, but also for societal development and sustainability. On one hand, global business increases the demand for managers for international assignment. On the other hand, emergent fears, such as terrorism, seem to be developing around the world, enhancing the risk of expatriates’ potential health problems. The purpose of this paper is to examine the relationships between the emergent concept of fear of expatriation with further workplace fears (economic crisis and dangerous working conditions and with mental health problems. The study uses a quantitative design. Self-reported data were collected from 265 Italian expatriate workers assigned to both Italian and worldwide projects. Structural equation model analyses showed that fear of expatriation mediates the relationship of mental health with fear of economic crisis and with perceived dangerous working conditions. As expected, in addition to fear, worries of expatriation are also related to further fears. Although the study is based on self-reports and the cross-sectional study design limits the possibility of making causal inferences, the new constructs introduced add to previous research.

  16. Expatriates’ Multiple Fears, from Terrorism to Working Conditions: Development of a Model

    Science.gov (United States)

    Giorgi, Gabriele; Montani, Francesco; Fiz-Perez, Javier; Arcangeli, Giulio; Mucci, Nicola

    2016-01-01

    Companies’ internationalization appears to be fundamental in the current globalized and competitive environment and seems important not only for organizational success, but also for societal development and sustainability. On one hand, global business increases the demand for managers for international assignment. On the other hand, emergent fears, such as terrorism, seem to be developing around the world, enhancing the risk of expatriates’ potential health problems. The purpose of this paper is to examine the relationships between the emergent concept of fear of expatriation with further workplace fears (economic crisis and dangerous working conditions) and with mental health problems. The study uses a quantitative design. Self-reported data were collected from 265 Italian expatriate workers assigned to both Italian and worldwide projects. Structural equation model analyses showed that fear of expatriation mediates the relationship of mental health with fear of economic crisis and with perceived dangerous working conditions. As expected, in addition to fear, worries of expatriation are also related to further fears. Although, the study is based on self-reports and the cross-sectional study design limits the possibility of making causal inferences, the new constructs introduced add to previous research. PMID:27790173

  17. Classical conditioning and pain: conditioned analgesia and hyperalgesia.

    Science.gov (United States)

    Miguez, Gonzalo; Laborda, Mario A; Miller, Ralph R

    2014-01-01

    This article reviews situations in which stimuli produce an increase or a decrease in nociceptive responses through basic associative processes and provides an associative account of such changes. Specifically, the literature suggests that cues associated with stress can produce conditioned analgesia or conditioned hyperalgesia, depending on the properties of the conditioned stimulus (e.g., contextual cues and audiovisual cues vs. gustatory and olfactory cues, respectively) and the proprieties of the unconditioned stimulus (e.g., appetitive, aversive, or analgesic, respectively). When such cues are associated with reducers of exogenous pain (e.g., opiates), they typically increase sensitivity to pain. Overall, the evidence concerning conditioned stress-induced analgesia, conditioned hyperalagesia, conditioned tolerance to morphine, and conditioned reduction of morphine analgesia suggests that selective associations between stimuli underlie changes in pain sensitivity.

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

    NARCIS (Netherlands)

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

    2008-01-01

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

  19. Cerebellum lesion impairs eyeblink-like classical conditioning in goldfish.

    Science.gov (United States)

    Gómez, A; Durán, E; Salas, C; Rodríguez, F

    2010-03-10

    The cerebellum of mammals is an essential component of the neural circuitry underlying classical conditioning of eyeblink and other discrete responses. Although the neuroanatomical organization of the cerebellum is notably well conserved in vertebrates, little is actually known about the cerebellar learning functions in nonmammal vertebrate groups. In this work we studied whether the cerebellum of teleost fish plays a critical role in the classical conditioning of a motor response. In Experiment 1, we classically conditioned goldfish in a procedure analogous to the eyeblink conditioning paradigm commonly used in mammals. Goldfish were able to learn to express an eyeblink-like conditioned response to a predictive light (conditioned stimulus) that was paired with a mild electric shock (unconditioned stimulus). The application of unpaired and extinction control procedures demonstrated that also in teleosts the learning of this motor response depends on associative rules. In Experiment 2 we studied whether classical conditioning of this response is critically dependent on the cerebellum and independent of telencephalic structures as occurs in mammals. Cerebellum lesion prevented the acquisition of the eyeblink-like conditioned response whereas telencephalon ablation did not impair the learning of this response. No deficit was observed following lesions in the performance of the unconditioned response or in the percentage of spontaneous responses. These results suggest that cerebellum ablation in goldfish affects a critical component of the circuitry necessary for the acquisition of the conditioned response but does not interfere with the ability of the animal to perform the response itself. The striking similarity in the role of cerebellum in classical conditioning of a motor response between teleost fish and mammals suggests that this learning function of the cerebellum could be a primitive feature of the vertebrate brain that has been conserved through evolution.

  20. Signal transduction mechanisms within the entorhinal cortex that support latent inhibition of cued fear conditioning.

    Science.gov (United States)

    Lewis, Michael C; Gould, Thomas J

    2007-10-01

    Latent inhibition is a phenomenon by which pre-exposure to a conditioned-stimulus (CS), prior to subsequent pairings of that same CS with an unconditioned-stimulus (US), results in decreased conditioned responding to the CS. Previous work in our laboratory has suggested that the entorhinal cortex is critically involved in the establishment of latent inhibition of cued fear conditioning. Furthermore, utilizing systemic pharmacology, we have demonstrated a role for of NMDA receptors, protein kinase A (PKA), and mitogen activated protein kinase (MAPK, also known as ERK) in latent inhibition of cued fear conditioning, but until now, where these cell signaling cascades are critically activated during latent inhibition of cued fear was unknown. Here, we use direct drug infusion to demonstrate that cell signaling via NMDA receptors, the cAMP/PKA pathway, and the MAPK pathway within the entorhinal cortex are critically involved in latent inhibition of cued fear conditioning. In the present study, CS pre-exposed mice received 20 CS pre-exposures 24h prior to two pairings of the same CS with a 0.53 mA foot shock US, while control animals receive no pre-exposure to the CS. The NMDA antagonist APV (0.25 or 2.5 microg/side), the cAMP inhibitor Rp-cAMP (1.8 or 18.0 microg/side), or the MAPK inhibitor U0126 (0.1 or 1.0 microg/side) were directly infused into the entorhinal cortex prior to pre-exposure. All three drugs produced dose-dependent disruptions in latent inhibition of cued fear conditioning. Importantly, none of the drugs had any effect on cued fear conditioning when administered on training day, suggesting that the effects of each of the drugs were specific to CS pre-exposure. These results are discussed in relation to the potential mechanisms of plasticity that support latent inhibition of cued fear conditioning.

  1. Role of classical conditioning in learning gastrointestinal symptoms

    Institute of Scientific and Technical Information of China (English)

    Ursula Stockhorst; Paul Enck; Sibylle Klosterhalfen

    2007-01-01

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

  2. Role of classical conditioning in learning gastrointestinal symptoms.

    Science.gov (United States)

    Stockhorst, Ursula; Enck, Paul; Klosterhalfen, Sibylle

    2007-07-01

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

  3. P50 suppression in human discrimination fear conditioning paradigm using danger and safety signals.

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    Kurayama, Taichi; Matsuzawa, Daisuke; Komiya, Zen; Nakazawa, Ken; Yoshida, Susumu; Shimizu, Eiji

    2012-04-01

    Auditory P50 suppression, which is assessed using a paired auditory stimuli (S1 and S2) paradigm to record the P50 mid-latency evoked potential, is assumed to reflect sensory gating. Recently, P50 suppression deficits were observed in patients with anxiety disorders, including panic disorder, post-traumatic stress disorder and obsessive-compulsive disorder, as we previously reported. The processes of fear conditioning are thought to play a role in the pathophysiology of anxiety disorders. In addition, we found that the P50 sensory gating mechanism might be physiologically associated with fear conditioning and extinction in a simple human fear-conditioning paradigm that involved a light signal as a conditioned stimulus (CS+). Our objective was to investigate the different patterns of P50 suppression in a discrimination fear-conditioning paradigm with both a CS+ (danger signal) and a CS- (safety signal). Twenty healthy volunteers were recruited. We measured the auditory P50 suppression in the control (baseline) phase, in the fear-acquisition phase, and in the fear-extinction phase using a discrimination fear-conditioning paradigm. Two-way (CSs vs. phase) Analysis of variance with repeated measures demonstrated a significant interaction between the two factors. Post-hoc LSD analysis indicated that the P50 S2/S1 ratio in the CS+ acquisition phase was significantly higher than that in the CS- acquisition phase. These results suggest that the auditory P50 sensory gating might differ according to the cognition of the properties (potentially dangerous or safe) of the perceived signal.

  4. From Pavlov to PTSD: the extinction of conditioned fear in rodents, humans, and anxiety disorders.

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    VanElzakker, Michael B; Dahlgren, M Kathryn; Davis, F Caroline; Dubois, Stacey; Shin, Lisa M

    2014-09-01

    Nearly 100 years ago, Ivan Pavlov demonstrated that dogs could learn to use a neutral cue to predict a biologically relevant event: after repeated predictive pairings, Pavlov's dogs were conditioned to anticipate food at the sound of a bell, which caused them to salivate. Like sustenance, danger is biologically relevant, and neutral cues can take on great salience when they predict a threat to survival. In anxiety disorders such as posttraumatic stress disorder (PTSD), this type of conditioned fear fails to extinguish, and reminders of traumatic events can cause pathological conditioned fear responses for decades after danger has passed. In this review, we use fear conditioning and extinction studies to draw a direct line from Pavlov to PTSD and other anxiety disorders. We explain how rodent studies have informed neuroimaging studies of healthy humans and humans with PTSD. We describe several genes that have been linked to both PTSD and fear conditioning and extinction and explain how abnormalities in fear conditioning or extinction may reflect a general biomarker of anxiety disorders. Finally, we explore drug and neuromodulation treatments that may enhance therapeutic extinction in anxiety disorders.

  5. From Pavlov to PTSD: The extinction of conditioned fear in rodents, humans, and in anxiety disorders

    Science.gov (United States)

    VanElzakker, Michael B.; Dahlgren, M. Kathryn; Davis, F. Caroline; Dubois, Stacey; Shin, Lisa M.

    2014-01-01

    Nearly 100 years ago, Ivan Pavlov demonstrated that dogs could learn to use a neutral cue to predict a biologically relevant event: after repeated predictive pairings, Pavlov's dogs were conditioned to anticipate food at the sound of a bell, which caused them to salivate. Like sustenance, danger is biologically relevant, and neutral cues can take on great salience when they predict a threat to survival. In anxiety disorders such as posttraumatic stress disorder (PTSD), this type of conditioned fear fails to extinguish, and reminders of traumatic events can cause pathological conditioned fear responses for decades after danger has passed. In this review, we use fear conditioning and extinction studies to draw a direct line from Pavlov to PTSD and other anxiety disorders. We explain how rodent studies have informed neuroimaging studies of healthy humans and humans with PTSD. We describe several genes that have been linked to both PTSD and fear conditioning and extinction and explain how abnormalities in fear conditioning or extinction may reflect a general biomarker of anxiety disorders. Finally, we explore drug and neuromodulation treatments that may enhance therapeutic extinction in anxiety disorders. PMID:24321650

  6. Allocation of cognitive processing capacity during human autonomic classical conditioning.

    Science.gov (United States)

    Dawson, M E; Schell, A M; Beers, J R; Kelly, A

    1982-09-01

    In each of two experiments, allocation of cognitive processing capacity was measured in college-student subjects during autonomic discrimination classical conditioning. A 7.0-sec delay paradigm was used to establish classically conditioned responses to a reinforced visual conditioned stimulus (CS+). Electrodermal responses were the primary measures of autonomic classical conditioning. Allocation of processing capacity was measured by monitoring performance on a secondary reaction-time (RT) task. The auditory secondary-task RT signal was presented before, and 300, 500, 3500, 6500, and 7500 msec following CS onset. The RT signal was also presented following properly and improperly cued shock unconditioned stimuli (UCSs). Significant discrimination classical conditioning was obtained in both experiments. Comparison with control subjects who did not receive the RT signals indicated that the presence of the RT signals did not interfere with the development of classical conditioning. Four principal findings were obtained with the secondary-task RT measure. First, RTs to signals presented during CS+ were consistently slower than RTs to signals presented during CS-. This finding indicates that greater capacity allocation occurred during CS+ than CS- and is consistent with recent cognitive interpretations of classical conditioning. Second, the largest capacity allocation (i.e., slowing of RTs) occurred 300 msec following CS+ onset. This finding is consistent with the notion that subjects are actively processing the signal properties of the CS+ at 300 msec following CS+ onset. Third, presentation of the UCS when improperly cued (following CS-) significantly increased capacity allocation, whereas presentation of the same UCS when properly cued (following CS+) did not affect capacity allocation. These findings indicate that subjects were actively prepared for the UCS following CS+ but not following CS- and that a surprising UCS elicits greater capacity allocation than does an

  7. Pharmacological depletion of serotonin in the basolateral amygdala complex reduces anxiety and disrupts fear conditioning.

    Science.gov (United States)

    Johnson, Philip L; Molosh, Andrei; Fitz, Stephanie D; Arendt, Dave; Deehan, Gerald A; Federici, Lauren M; Bernabe, Cristian; Engleman, Eric A; Rodd, Zachary A; Lowry, Christopher A; Shekhar, Anantha

    2015-11-01

    The basolateral and lateral amygdala nuclei complex (BLC) is implicated in a number of emotional responses including conditioned fear and social anxiety. Based on previous studies demonstrating that enhanced serotonin release in the BLC leads to increased anxiety and fear responses, we hypothesized that pharmacologically depleting serotonin in the BLC using 5,7-dihydroxytryptamine (5,7-DHT) injections would lead to diminished anxiety and disrupted fear conditioning. To test this hypothesis, 5,7-DHT(a serotonin-depleting agent) was bilaterally injected into the BLC. Desipramine (a norepinephrine reuptake inhibitor) was systemically administered to prevent non-selective effects on norepinephrine. After 5days, 5-7-DHT-treated rats showed increases in the duration of social interaction (SI) time, suggestive of reduced anxiety-like behavior. We then used a cue-induced fear conditioning protocol with shock as the unconditioned stimulus and tone as the conditioned stimulus for rats pretreated with bilateral 5,7-DHT, or vehicle, injections into the BLC. Compared to vehicle-treated rats, 5,7-DHT rats had reduced acquisition of fear during conditioning (measured by freezing time during tone), also had reduced fear retrieval/recall on subsequent testing days. Ex vivo analyses revealed that 5,7-DHT reduced local 5-HT concentrations in the BLC by ~40% without altering local norepinephrine or dopamine concentrations. These data provide additional support for 5-HT playing a critical role in modulating anxiety-like behavior and fear-associated memories through its actions within the BLC.

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

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

    2004-08-01

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

  9. A Different Recruitment of the Lateral and Basolateral Amygdala Promotes Contextual or Elemental Conditioned Association in Pavlovian Fear Conditioning

    Science.gov (United States)

    Calandreau, Ludovic; Desmedt, Aline; Decorte, Laurence; Jaffard, Robert

    2005-01-01

    Convergent data suggest dissociated roles for the lateral (LA) and basolateral (BLA) amygdaloid nuclei in fear conditioning, depending on whether a discrete conditioned stimulus (CS)-unconditional stimulus (US) or context-US association is considered. Here, we show that pretraining inactivation of the BLA selectively impaired conditioning to…

  10. Normal eyeblink classical conditioning in patients with fixed dystonia

    NARCIS (Netherlands)

    Janssen, S.; Veugen, L.C.; Hoffland, B.S.; Kassavetis, P.; Rooijen, D.E. van; Stegeman, D.F.; Edwards, Mark J.; Hilten, J.J. van; Warrenburg, B.P.C. van de

    2014-01-01

    Fixed dystonia without evidence of basal ganglia lesions or neurodegeneration typically affects young women following minor peripheral trauma. We use eyeblink classical conditioning (EBCC) to study whether cerebellar functioning is abnormal in patients with fixed dystonia, since this is part of the

  11. [The Manifestation of the Anxiety during Fear Conditioning in Wistar Rats].

    Science.gov (United States)

    Pavlova, I V; Rysakova, M P

    2015-01-01

    In order to identify the correlation between anxiety and conditioned fear, the behavior of the same male Wistar rats was compared in three anxiety tests (open field, light-dark box and elevated plus-maze) and in Pavlovian auditory fear conditioning paradigm using correlation, factor and variance analyses. The correlation between anxiety/bravery and locomotion indexes in different tests was not revealed. Positive correlations between grooming, urinations and defecations, rearing in three tests were revealed. These data suggest that animals reacted to various tests differently, resulting, apparently in the emergence of different anxiety levels, specific for each test. Vegetative reactions, inclination to exploration and substituting behavior were more stable characteristics of rats. Anxiety behavior in elevated plus-maze correlated to freezing response to context after fear conditioning, while high-anxiety rats had higher level of freezing to context than low-anxiety rats. The higher freezing response to sound after fear conditioning was found in rats with middle locomotor activity in open field. Conditioned fear to the context and to the sound was associated with different forms of rat anxiety during different tests.

  12. The development of an attentional bias for angry faces following Pavlovian fear conditioning.

    Science.gov (United States)

    Pischek-Simpson, Leah K; Boschen, Mark J; Neumann, David L; Waters, Allison M

    2009-04-01

    Although it is well documented that fear responses develop following aversive Pavlovian conditioning, it is unclear whether fear learning also manifests in the form of attentional biases for fear-related stimuli. Boschen, Parker, and Neumann (Boschen, M. J., Parker, I., & Neumann, D. L. (2007). Changes in implicit associations do not occur simultaneously to Pavlovian conditioning of physiological anxiety responses. Journal of Anxiety Disorders, 21, 788-803.) showed that despite the acquisition of differential skin conductance conditioned responses to angry faces paired (CS+) and unpaired (CS-) with an aversive shock, development of implicit associations was not subsequently observed on the Implicit Association Test. In the present study, participants (N=76) were assigned either to a Shock or NoShock group and completed a similar aversive Pavlovian conditioning procedure with angry face CS+ and CS- stimuli. Participants next completed a visual probe task in which the angry face CS+ and CS- stimuli were paired with angry face control stimuli and neutral faces. Results confirmed that differential fear conditioning was observed in the Shock group but not in the NoShock group, and that the Shock group subsequently showed a selective attentional bias for the angry face CS+ compared with the CS- and control stimuli during the visual probe task. The findings confirm the interplay between learning-based mechanisms and cognitive processes, such as attentional biases, in models of fear acquisition and have implications for treatment of the anxiety disorders.

  13. Transference in view of a classical conditioning model.

    Science.gov (United States)

    Rabinovich, Merav; Kacen, Lea

    2012-01-01

    This article presents a qualitative metasynthetic study, addressing 33 transference case studies, that investigates the interrelationship of the transference concept from psychoanalysis and cognitive-behavioral concepts in an attempt to construct a theoretical platform for clinical integration. Relationship between categories analysis was used to compare Luborsky's (1998) transference components (wish, response from other, and response of self) and cognitive-behavioral ones. Results showed reciprocal relations between transference and classical conditioning. Furthermore, explicit occurrences of distorted thinking due to overgeneralization were found in more than 90% of the cases. A conceptual model describes transference as a conditioned response activated by thematic conditioning, a particular case of classical conditioning that repeatedly pairs a given interpersonal situation with internal thematic stimuli, thus shaping the person's narrative. Theoretical and practical implications are discussed as well.

  14. The role of the nucleus basalis magnocellularis in fear conditioning consolidation in the rat.

    Science.gov (United States)

    Baldi, Elisabetta; Mariottini, Chiara; Bucherelli, Corrado

    2007-12-01

    The nucleus basalis magnocellularis (NBM) is known to be involved in the memorization of several conditioned responses. To investigate the role of the NBM in fear conditioning memorization, this neural site was subjected to fully reversible tetrodotoxin (TTX) inactivation during consolidation in adult male Wistar rats that had undergone fear training to acoustic conditioned stimulus (CS) and context. TTX was stereotaxically administered to different groups of rats at increasing intervals after the acquisition session. Memory was assessed as the conditioned freezing duration measured during retention testing, always performed 72 and 96 h after TTX administration. In this way, there was no interference with normal NBM function during either acquisition or retrieval phases, allowing any amnesic effect to be due only to consolidation disruption. The results show that for contextual fear response memory consolidation, NBM functional integrity is necessary up to 24 h post-acquisition. On the other hand, NBM functional integrity was shown to be necessary for memory consolidation of the acoustic CS fear response only immediately after acquisition and not 24-h post-acquisition. The present findings help to elucidate the role of the NBM in memory consolidation and better define the neural circuits involved in fear memories.

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

    NARCIS (Netherlands)

    Kaag, A.M.; Levar, N.; Woutersen, K.; Homberg, J.R.; Brink, W. van den; Reneman, L.; Wingen, G. van

    2016-01-01

    OBJECTIVE: The authors investigated whether cocaine use disorder is associated with abnormalities in the neural underpinnings of aversive conditioning and extinction learning, as these processes may play an important role in the development and persistence of drug abuse. METHOD: Forty male regular c

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

    Directory of Open Access Journals (Sweden)

    Hidehiro Watanabe

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

  17. In vitro classical conditioning of abducens nerve discharge in turtles.

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    Keifer, J; Armstrong, K E; Houk, J C

    1995-07-01

    In vitro classical conditioning of abducens nerve activity was performed using an isolated turtle brainstem-cerebellum preparation by direct stimulation of the cranial nerves. Using a delayed training procedure, the in vitro preparation was presented with paired stimuli consisting of a 1 sec train stimulus applied to the auditory nerve (CS), which immediately preceded a single shock US applied to the trigeminal nerve. Conditioned and unconditioned responses were recorded in the ipsilateral abducens nerve. Acquisition exhibited a positive slope of conditioned responding in 60% of the preparations. Application of unpaired stimuli consisting of CS-alone, alternate CS and US, or backward conditioning failed to result in conditioning, or resulted in extinction of CRs. Latencies of CR onset were timed such that they occurred midway through the CS. Activity-dependent uptake of the dye sulforhodamine was used to examine the spatial distribution of neurons labeled during conditioning. These data showed label in the cerebellum and red nucleus during conditioning whereas these regions failed to label during unconditioned responses. Furthermore, the principal abducens nucleus labeled heavily during conditioning. These findings suggest the feasibility of examining classical conditioning in a vertebrate in vitro brainstem-cerebellum preparation. It is postulated that the abducens nerve CR represents a behavioral correlate of a blink-related eye movement. Multiple sites of conditioning are hypothesized, including the cerebellorubral circuitry and brainstem pathways that activate the principal abducens nucleus.

  18. Appetitive behavioral traits and stimulus intensity influence maintenance of conditioned fear

    Directory of Open Access Journals (Sweden)

    Megan eOlshavsky

    2013-12-01

    Full Text Available Individual differences in appetitive learning have long been reported, and generally divide into two classes of responses: cue- vs. reward-directed. The influence of cue- vs. reward-directed phenotypes on aversive cue processing, is less well understood. In the current study, we first categorized rats based on their predominant cue-directed orienting responses during appetitive Pavlovian conditioning. Then, we investigated the effect of phenotype on the latency to exit a familiar dark environment and enter an unfamiliar illuminated open field. Next, we examined whether the two phenotypes responded differently to a reconsolidation updating manipulation (retrieval+extinction after fear conditioning. We report that the rats with a cue-directed (orienting phenotype differentially respond to the open field, and also to fear conditioning, depending on US-intensity. In addition, our findings suggest that, regardless of appetitive phenotype or shock intensity, extinction within the reconsolidation window prevents spontaneous recovery of fear.

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

    Science.gov (United States)

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

    2009-01-01

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

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

    Science.gov (United States)

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

    2008-01-01

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

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

    Science.gov (United States)

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

    2012-01-18

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

  2. Mice selectively bred for High and Low fear behavior show differences in the number of pMAPK (p44/42 ERK) expressing neurons in lateral amygdala following Pavlovian fear conditioning.

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    Coyner, Jennifer; McGuire, Jennifer L; Parker, Clarissa C; Ursano, Robert J; Palmer, Abraham A; Johnson, Luke R

    2014-07-01

    Individual variability in the acquisition, consolidation and extinction of conditioned fear potentially contributes to the development of fear pathology including posttraumatic stress disorder (PTSD). Pavlovian fear conditioning is a key tool for the study of fundamental aspects of fear learning. Here, we used a selected mouse line of High and Low Pavlovian conditioned fear created from an advanced intercrossed line (AIL) in order to begin to identify the cellular basis of phenotypic divergence in Pavlovian fear conditioning. We investigated whether phosphorylated MAPK (p44/42 ERK/MAPK), a protein kinase required in the amygdala for the acquisition and consolidation of Pavlovian fear memory, is differentially expressed following Pavlovian fear learning in the High and Low fear lines. We found that following Pavlovian auditory fear conditioning, High and Low line mice differ in the number of pMAPK-expressing neurons in the dorsal sub nucleus of the lateral amygdala (LAd). In contrast, this difference was not detected in the ventral medial (LAvm) or ventral lateral (LAvl) amygdala sub nuclei or in control animals. We propose that this apparent increase in plasticity at a known locus of fear memory acquisition and consolidation relates to intrinsic differences between the two fear phenotypes. These data provide important insights into the micronetwork mechanisms encoding phenotypic differences in fear. Understanding the circuit level cellular and molecular mechanisms that underlie individual variability in fear learning is critical for the development of effective treatment of fear-related illnesses such as PTSD.

  3. The Role of Muscarinic and Nicotinic Cholinergic Neurotransmission in Aversive Conditioning: Comparing Pavlovian Fear Conditioning and Inhibitory Avoidance

    Science.gov (United States)

    Tinsley, Matthew R.; Quinn, Jennifer J.; Fanselow, Michael S.

    2004-01-01

    Aversive conditioning is an ideal model for studying cholinergic effects on the processes of learning and memory for several reasons. First, deficits produced by selective lesions of the anatomical structures shown to be critical for Pavlovian fear conditioning and inhibitory avoidance (such as the amygdala and hippocampus) resemble those deficits…

  4. The development of cued versus contextual conditioning in a predictable and an unpredictable human fear conditioning preparation

    NARCIS (Netherlands)

    C. Iberico; D. Vansteenwegen; B. Vervliet; T. Dirikx; V. Marescau; D. Hermans

    2008-01-01

    In this human fear conditioning study, the online development of conditioned US-expectancy to discrete cues and background contexts was measured in two groups. In the paired group (n = 30), the CS was systematically followed by an aversive shock (US). In the unpaired group (n = 30), CS and US were p

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

    Science.gov (United States)

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

    2016-09-01

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

  6. Pavlovian fear conditioning activates a common pattern of neurons in the lateral amygdala of individual brains.

    Directory of Open Access Journals (Sweden)

    Hadley C Bergstrom

    Full Text Available Understanding the physical encoding of a memory (the engram is a fundamental question in neuroscience. Although it has been established that the lateral amygdala is a key site for encoding associative fear memory, it is currently unclear whether the spatial distribution of neurons encoding a given memory is random or stable. Here we used spatial principal components analysis to quantify the topography of activated neurons, in a select region of the lateral amygdala, from rat brains encoding a Pavlovian conditioned fear memory. Our results demonstrate a stable, spatially patterned organization of amygdala neurons are activated during the formation of a Pavlovian conditioned fear memory. We suggest that this stable neuronal assembly constitutes a spatial dimension of the engram.

  7. Pavlovian fear conditioning activates a common pattern of neurons in the lateral amygdala of individual brains.

    Science.gov (United States)

    Bergstrom, Hadley C; McDonald, Craig G; Johnson, Luke R

    2011-01-12

    Understanding the physical encoding of a memory (the engram) is a fundamental question in neuroscience. Although it has been established that the lateral amygdala is a key site for encoding associative fear memory, it is currently unclear whether the spatial distribution of neurons encoding a given memory is random or stable. Here we used spatial principal components analysis to quantify the topography of activated neurons, in a select region of the lateral amygdala, from rat brains encoding a Pavlovian conditioned fear memory. Our results demonstrate a stable, spatially patterned organization of amygdala neurons are activated during the formation of a Pavlovian conditioned fear memory. We suggest that this stable neuronal assembly constitutes a spatial dimension of the engram.

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

    Science.gov (United States)

    Sevenster, Dieuwke; Beckers, Tom; Kindt, Merel

    2014-01-01

    There is conflicting evidence as to whether awareness is required for conditioning of the skin conductance response (SCR). Recently, Schultz and Helmstetter (2010) reported SCR conditioning in contingency unaware participants by using difficult to discriminate stimuli. These findings are in stark contrast with other observations in human fear conditioning research, showing that SCR predominantly reflects contingency learning. Therefore, we repeated the study by Schultz and Helmstetter and additionally measured conditioning of the startle response, which seems to be less sensitive to declarative knowledge than SCR. While we solely observed SCR conditioning in participants who reported awareness of the contingencies (n = 16) and not in the unaware participants (n = 18), we observed startle conditioning irrespective of awareness. We conclude that SCR but not startle conditioning depends on conscious discriminative fear learning.

  9. Classical olfactory conditioning in the oriental fruit fly, Bactrocera dorsalis.

    Science.gov (United States)

    Liu, Jia Li; Chen, Xiao Yan; Zeng, Xin Nian

    2015-01-01

    The oriental fruit fly, Bactrocera dorsalis, is a serious pest of fruits and vegetables. Methyl eugenol (ME), a male attractant, is used to against this fly by mass trapping. Control effect may be influenced by learning, which could modify the olfactory response of the fly to this attractant. To collect the behavioral evidence, studies on the capability of this fly for olfactory learning are necessary. We investigated olfactory learning in male flies with a classical olfactory conditioning procedure using restrained individuals under laboratory conditions. The acquisition of the proboscis extension reflex was used as the criterion for conditioning. A high conditioned response level was found in oriental fruit flies when an odor was presented in paired association with a sucrose reward but not when the odor and sucrose were presented unpaired. We also found that the conditioning performance was influenced by the odor concentration, intertrial interval, and starvation time. A slight sensitization elicited by imbibing sucrose was observed. These results indicate that oriental fruit flies have a high capacity to form an olfactory memory as a result of classical conditioning.

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

    Science.gov (United States)

    Nasser, Helen M.; McNally, Gavan P.

    2013-01-01

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

  11. Avoided by association: acquisition, extinction, and renewal of avoidance tendencies toward conditioned fear stimuli

    NARCIS (Netherlands)

    A.M. Krypotos; M. Effting; I. Arnaudova; M. Kindt; T. Beckers

    2013-01-01

    Traditional theoretical models hold that avoidance reflects the interplay of Pavlovian and instrumental learning. Here we suggest that avoidance tendencies to intrinsically neutral cues may be established by mere Pavlovian association. Following fear conditioning, in which pictures of one object wer

  12. Effects of Post-Training Hippocampal Injections of Midazolam on Fear Conditioning

    Science.gov (United States)

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

    2005-01-01

    Benzodiazepines have been useful tools for investigating mechanisms underlying learning and memory. The present set of experiments investigates the role of hippocampal GABA[subscript A]/benzodiazepine receptors in memory consolidation using Pavlovian fear conditioning. Rats were prepared with cannulae aimed at the dorsal hippocampus and trained…

  13. Fast, transient cardiac accelerations and decelerations during fear conditioning in rats

    NARCIS (Netherlands)

    Knippenberg, J.M.J.; Barry, R.J.; Kuniecki, M.J.; Luijtelaar, E.L.J.M. van

    2011-01-01

    The current study reports on a number of heart rate responses observed in rats subjected to a discriminatory Pavlovian fear conditioning procedure. Rats learned that a series of six auditory pips was followed by a footshock when presented alone, but not when the pip series was preceded by a visual s

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

    Science.gov (United States)

    Bredy, Timothy W.; Barad, Mark

    2008-01-01

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

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Science.gov (United States)

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

    2010-01-01

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

  17. Inhibition of prefrontal protein synthesis following recall does not disrupt memory for trace fear conditioning

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    Dash Pramod K

    2006-10-01

    Full Text Available Abstract Background The extent of similarity between consolidation and reconsolidation is not yet fully understood. One of the differences noted is that not every brain region involved in consolidation exhibits reconsolidation. In trace fear conditioning, the hippocampus and the medial prefrontal cortex (mPFC are required for consolidation of long-term memory. We have previously demonstrated that trace fear memory is susceptible to infusion of the protein synthesis inhibitor anisomycin into the hippocampus following recall. In the present study, we examine whether protein synthesis inhibition in the mPFC following recall similarly results in the observation of reconsolidation of trace fear memory. Results Targeted intra-mPFC infusions of anisomycin or vehicle were performed immediately following recall of trace fear memory at 24 hours, or at 30 days, following training in a one-day or a two-day protocol. The present study demonstrates three key findings: 1 trace fear memory does not undergo protein synthesis dependent reconsolidation in the PFC, regardless of the intensity of the training, and 2 regardless of whether the memory is recent or remote, and 3 intra-mPFC inhibition of protein synthesis immediately following training impaired remote (30 days memory. Conclusion These results suggest that not all structures that participate in memory storage are involved in reconsolidation. Alternatively, certain types of memory-related information may reconsolidate, while other components of memory may not.

  18. Rapid learning dynamics in individual honeybees during classical conditioning

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    Evren ePamir

    2014-09-01

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

  19. Oxytocin and Social Support as Synergistic Inhibitors of Aversive Fear Conditioning and Fear-Potentiated Startle in Male Rats

    Science.gov (United States)

    2011-05-01

    Davis M (1997). Evidence of contextual fear after lesions of the hippocampus : a disruption of freezing but not fear-potentiated startle. f Neurosci 17...monkeys by morphine , diazepam, and buspirone. Bioi Psychiatry 61: 389-395.     Appendix  2:     2009 MHRF Oral  presentation  #S3

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

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    Vervliet, Bram

    2008-03-01

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

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    A core feature of autism spectrum disorders is the impairment in social interactions. Among other brain regions, a deficit in amygdala processing has been suggested to underlie this impairment, but whether the amygdala is processing fear abnormally in autism, is yet not clear. We used the valproic......-treated animals displayed several symptoms common to autism, among them impaired social interactions and increased repetitive behaviors. Furthermore, VPA-treated rats were more anxious and exhibited abnormally high and longer lasting fear memories, which were overgeneralized and harder to extinguish....... On the cellular level, the amygdala was hyperreactive to electrical stimulation and displayed boosted synaptic plasticity as well as a deficit in inhibition. We show for the first time enhanced, overgeneralized and resistant conditioned fear memories in an animal model of autism. Such hyperfear could be caused...

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

    Science.gov (United States)

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

    2016-01-01

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

  3. Amygdala kindling disrupts trace and delay fear conditioning with parallel changes in Fos protein expression throughout the limbic brain.

    Science.gov (United States)

    Botterill, J J; Fournier, N M; Guskjolen, A J; Lussier, A L; Marks, W N; Kalynchuk, L E

    2014-04-18

    Amygdala kindling is well known to increase unconditioned fear and anxiety. However, relatively little is known about whether this form of kindling causes functional changes within the neural circuitry that mediates fear learning and the retrieval of fear memories. To address this issue, we examined the effect of short- (i.e., 30 stimulations) and long-term (i.e., 99 stimulations) amygdala kindling in rats on trace and delay fear conditioning, which are aversive learning tasks that rely predominantly on the hippocampus and amygdala, respectively. After memory retrieval, we analyzed the pattern of neural activity with Fos, the protein product of the immediate early gene c-fos. We found that kindling had no effect on acquisition of the trace fear conditioning task but it did selectively impair retrieval of this fear memory. In contrast, kindling disrupted both acquisition and retrieval of fear memory in the delay fear conditioning task. We also found that kindling-induced impairments in memory retrieval were accompanied by decreased Fos expression in several subregions of the hippocampus, parahippocampus, and amygdala. Interestingly, decreased freezing in the trace conditioning task was significantly correlated with dampened Fos expression in hippocampal and parahippocampal regions whereas decreased freezing in the delay conditioning task was significantly correlated with dampened Fos expression in hippocampal, parahippocampal, and amygdaloid circuits. Overall, these results suggest that amygdala kindling promotes functional changes in brain regions involved in specific types of fear learning and memory.

  4. Epigenetic modulation of Homer1a transcription regulation in amygdala and hippocampus with pavlovian fear conditioning.

    Science.gov (United States)

    Mahan, Amy L; Mou, Liping; Shah, Nirali; Hu, Jia-Hua; Worley, Paul F; Ressler, Kerry J

    2012-03-28

    The consolidation of conditioned fear involves upregulation of genes necessary for long-term memory formation. An important question remains as to whether this results in part from epigenetic regulation and chromatin modulation. We examined whether Homer1a, which is required for memory formation, is necessary for Pavlovian cued fear conditioning, whether it is downstream of BDNF-TrkB activation, and whether this pathway utilizes histone modifications for activity-dependent transcriptional regulation. We initially found that Homer1a knock-out mice exhibited deficits in cued fear conditioning (5 tone-shock presentations with 70 dB, 6 kHz tones and 0.5 s, 0.6 mA footshocks). We then demonstrated that: (1) Homer1a mRNA increases after fear conditioning in vivo within both amygdala and hippocampus of wild-type mice; (2) it increases after BDNF application to primary hippocampal and amygdala cultures in vitro; and (3) these increases are dependent on transcription and MAPK signaling. Furthermore, using chromatin immunoprecipitation we found that both in vitro and in vivo manipulations result in decreases in Homer1 promoter H3K9 methylation in amygdala cells but increases in Homer1 promoter H3 acetylation in hippocampal cells. However, no changes were observed in H4 acetylation or H3K27 dimethylation. Inhibition of histone deacetylation by sodium butyrate enhanced contextual but not cued fear conditioning and enhanced Homer1 H3 acetylation in the hippocampus. These data provide evidence for dynamic epigenetic regulation of Homer1a following BDNF-induced plasticity and during a BDNF-dependent learning process. Furthermore, upregulation of this gene may be regulated through distinct epigenetic modifications in the hippocampus and amygdala.

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

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    Ralf eVeit

    2013-10-01

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

  6. Resting-state connectivity of the amygdala is altered following Pavlovian fear conditioning.

    Science.gov (United States)

    Schultz, Douglas H; Balderston, Nicholas L; Helmstetter, Fred J

    2012-01-01

    Neural plasticity in the amygdala is necessary for the acquisition and storage of memory in Pavlovian fear conditioning, but most neuroimaging studies have focused only on stimulus-evoked responses during the conditioning session. This study examined changes in the resting-state functional connectivity (RSFC) of the amygdala before and after Pavlovian fear conditioning, an emotional learning task. Behavioral results from the conditioning session revealed that participants learned normally and fMRI data recorded during learning identified a number of stimulus-evoked changes that were consistent with previous work. A direct comparison between the pre- and post-conditioning amygdala connectivity revealed a region of dorsal prefrontal cortex (PFC) in the superior frontal gyrus that showed a significant increase in connectivity following the conditioning session. A behavioral measure of explicit memory performance was positively correlated with the change in amygdala connectivity within a neighboring region in the superior frontal gyrus. Additionally, an implicit autonomic measure of conditioning was positively correlated with the change in connectivity between the amygdala and the anterior cingulate cortex (ACC). The resting-state data show that amygdala connectivity is altered following Pavlovian fear conditioning and that these changes are also related to behavioral outcomes. These alterations may reflect the operation of a consolidation process that strengthens neural connections to support memory after the learning event.

  7. Resting-state connectivity of the amygdala is altered following Pavlovian fear conditioning

    Directory of Open Access Journals (Sweden)

    Douglas H Schultz

    2012-08-01

    Full Text Available Neural plasticity in the amygdala is necessary for the acquisition and storage of memory in Pavlovian fear conditioning, but most neuroimaging studies have focused only on stimulus-evoked responses during the conditioning session. This study examined changes in the resting-state functional connectivity (RSFC of the amygdala before and after Pavlovian fear conditioning, an emotional learning task. Behavioral results from the conditioning session revealed that participants learned normally and FMRI data recorded during learning identified a number of stimulus-evoked changes that were consistent with previous work. A direct comparison between the pre and post-conditioning amygdala connectivity revealed a region of dorsal prefrontal cortex (PFC in the superior frontal gyrus that showed a significant increase in connectivity following the conditioning session. A behavioral measure of explicit memory performance was positively correlated with the change in amygdala connectivity within a neighboring region in the superior frontal gyrus. Additionally, an implicit autonomic measure of conditioning was positively correlated with the change in connectivity between the amygdala and the anterior cingulate cortex. The resting-state data show that amygdala connectivity is altered following Pavlovian fear conditioning and that these changes are also related to behavioral outcomes. These alterations may reflect the operation of a consolidation process that strengthens neural connections to support memory after the learning event.

  8. Application of Pavlovian higher-order conditioning to the analysis of the neural substrates of fear conditioning.

    Science.gov (United States)

    Gewirtz, J C; Davis, M

    1998-01-01

    In Pavlovian first-order conditioning, a conditioned response is acquired by pairing a neutral stimulus (S1) with a stimulus that has innate motivational value. In higher-order conditioning, a neutral stimulus (S2) is paired with S1 either after (second-order conditioning) or before (sensory preconditioning) first-order conditioning has been acquired. Thus, in higher-order conditioning the motivational value of the reinforcer is acquired rather than innate. This review describes some of the potential uses of higher-order conditioning in investigating the neural substrates of fearful memories. First, because in second-order fear conditioning S2 is not paired directly with a painful stimulus, any effect of a treatment on the acquisition of fear cannot be attributed to the treatment's possible effects on transmission of nociceptive information. Second, higher-order conditioning provides opportunities for analyzing where and how different types of events, or different aspects of the same events, are represented in the brain.

  9. WIN 55212-2 impairs contextual fear conditioning through the activation of CB1 cannabinoid receptors.

    Science.gov (United States)

    Pamplona, Fabrício Alano; Takahashi, Reinaldo Naoto

    The memory deficits induced by cannabinoid agonists have been found in several behavioral paradigms. Nevertheless, there is evidence that not all types of memory are impaired after cannabinoid administration. The aim of this study was to investigate whether the cannabinoid agonist WIN 55212-2 (WIN) is able to influence the acquisition of fear conditioning using tone and contextual versions. For tone-fear conditioning, male Wistar rats were placed in the conditioning chamber and after 3 min, a sound (CS) was presented for 10s that terminated with a 1-s electric footshock (1.5 mA). For contextual-fear conditioning, a similar procedure was used but no sound was presented. Twenty-four hours after, the animals were re-exposed to the respective CS (tone or conditioning chamber) and the freezing behavior was registered. A subsequent experiment investigated a possible state-dependent effect of WIN by administering WIN or control solution 30 min before conditioning and before testing. WIN (2.5 and 5.0 mg/kg) administered i.p. 30 min before impaired contextual fear conditioning but did not modify the freezing behavior elicited by tone presentation. These animals did not show any state-dependent effects of WIN. Further, the impaired contextual conditioning was prevented by preadministration of SR141716A (1.0 mg/kg, i.p.) or SR147778 (1.0 mg/kg, i.p.), selective cannabinoid CB1 receptor antagonists. The present findings highlight that cannabinoid agonists effects are selective for the hippocampus-dependent aversive memories in rats. This effect appears to be related to the activation of CB1 cannabinoid receptors and confirms that cannabinoids might provide a novel approach for the treatment of unpleasant memories.

  10. Contributions of the amygdala central nucleus and ventrolateral periaqueductal grey to freezing and instrumental suppression in Pavlovian fear conditioning.

    Science.gov (United States)

    McDannald, Michael A

    2010-07-29

    In Pavlovian fear conditioning animals receive pairings of a neutral cue and an aversive stimulus such as an electric foot-shock. Through such pairings, the cue will come to elicit a central state of fear that produces a variety of autonomic and behavioral responses, among which are conditioned freezing and suppression of instrumental responding, termed conditioned suppression. The central nucleus of the amygdala (CeA) and the ventrolateral periaqueductal grey (vlPAG) has been strongly implicated in the acquisition and expression of conditioned fear. However, previous work suggests different roles for the CeA and vlPAG in fear learning maybe revealed when fear is assessed with conditioned freezing or conditioned suppression. To further explore this possibility we gave rats selective lesions of either the CeA or vlPAG and trained them in Pavlovian first-order fear conditioning as well as Pavlovian second-order fear conditioning. We concurrently assessed the acquisition of conditioned freezing and conditioned suppression. We found that vlPAG and CeA lesions impaired both first- and second-order conditioned freezing. VlPAG lesions did not impair, and CeA lesions only transiently impaired, first-order conditioned suppression. However, both vlPAG and CeA lesions impaired second-order conditioned suppression. These results suggest that the CeA and vlPAG are critically important to expressing fear through conditioned freezing but play different and less critical roles in expressing fear through conditioned suppression.

  11. Classic conditioning of the ventilatory responses in rats.

    Science.gov (United States)

    Nsegbe, E; Vardon, G; Perruchet, P; Gallego, J

    1997-10-01

    Recent authors have stressed the role of conditioning in the control of breathing, but experimental evidence of this role is still sparse and contradictory. To establish that classic conditioning of the ventilatory responses can occur in rats, we performed a controlled experiment in which a 1-min tone [conditioned stimulus (CS)] was paired with a hypercapnic stimulus [8.5% CO2, unconditioned stimulus (US)]. The experimental group (n = 9) received five paired CS-US presentations, followed by one CS alone to test conditioning. This sequence was repeated six times. The control group (n = 7) received the same number of CS and US, but each US was delivered 3 min after the CS. We observed that after the CS alone, breath duration was significantly longer in the experimental than in the control group and mean ventilation was significantly lower, thus showing inhibitory conditioning. This conditioning may have resulted from the association between the CS and the inhibitory and aversive effects of CO2. The present results confirmed the high sensitivity of the respiratory controller to conditioning processes.

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

    Science.gov (United States)

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

    2016-02-01

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

  13. Lifelong disturbance of serotonin transporter functioning results in fear learning deficits : Reversal by blockade of CRF1 receptors

    NARCIS (Netherlands)

    Bijlsma, Elisabeth Y; Hendriksen, Hendrikus; Baas, Johanna M P; Millan, Mark J; Groenink, Lucianne

    2015-01-01

    The inability to associate aversive events with relevant cues (i.e. fear learning) may lead to maladaptive anxiety. To further study the role of the serotonin transporter (SERT) in fear learning, classical fear conditioning was studied in SERT knockout rats (SERT(-/-)) using fear potentiation of the

  14. Classical and quantum initial conditions for Higgs inflation

    Directory of Open Access Journals (Sweden)

    Alberto Salvio

    2015-11-01

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

  15. Lack of predictive power of trait fear and anxiety for conditioned pain modulation (CPM).

    Science.gov (United States)

    Horn-Hofmann, Claudia; Priebe, Janosch A; Schaller, Jörg; Görlitz, Rüdiger; Lautenbacher, Stefan

    2016-12-01

    In recent years the association of conditioned pain modulation (CPM) with trait fear and anxiety has become a hot topic in pain research due to the assumption that such variables may explain the low CPM efficiency in some individuals. However, empirical evidence concerning this association is still equivocal. Our study is the first to investigate the predictive power of fear and anxiety for CPM by using a well-established psycho-physiological measure of trait fear, i.e. startle potentiation, in addition to two self-report measures of pain-related trait anxiety. Forty healthy, pain-free participants (female: N = 20; age: M = 23.62 years) underwent two experimental blocks in counter-balanced order: (1) a startle paradigm with affective picture presentation and (2) a CPM procedure with hot water as conditioning stimulus (CS) and contact heat as test stimulus (TS). At the end of the experimental session, pain catastrophizing (PCS) and pain anxiety (PASS) were assessed. PCS score, PASS score and startle potentiation to threatening pictures were entered as predictors in a linear regression model with CPM magnitude as criterion. We were able to show an inhibitory CPM effect in our sample: pain ratings of the heat stimuli were significantly reduced during hot water immersion. However, CPM was neither predicted by self-report of pain-related anxiety nor by startle potentiation as psycho-physiological measure of trait fear. These results corroborate previous negative findings concerning the association between trait fear/anxiety and CPM efficiency and suggest that shifting the focus from trait to state measures might be promising.

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

    Science.gov (United States)

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

    2015-01-01

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

  17. Gene networks associated with conditional fear in mice identified using a systems genetics approach

    Directory of Open Access Journals (Sweden)

    Eskin Eleazar

    2011-03-01

    Full Text Available Abstract Background Our understanding of the genetic basis of learning and memory remains shrouded in mystery. To explore the genetic networks governing the biology of conditional fear, we used a systems genetics approach to analyze a hybrid mouse diversity panel (HMDP with high mapping resolution. Results A total of 27 behavioral quantitative trait loci were mapped with a false discovery rate of 5%. By integrating fear phenotypes, transcript profiling data from hippocampus and striatum and also genotype information, two gene co-expression networks correlated with context-dependent immobility were identified. We prioritized the key markers and genes in these pathways using intramodular connectivity measures and structural equation modeling. Highly connected genes in the context fear modules included Psmd6, Ube2a and Usp33, suggesting an important role for ubiquitination in learning and memory. In addition, we surveyed the architecture of brain transcript regulation and demonstrated preservation of gene co-expression modules in hippocampus and striatum, while also highlighting important differences. Rps15a, Kif3a, Stard7, 6330503K22RIK, and Plvap were among the individual genes whose transcript abundance were strongly associated with fear phenotypes. Conclusion Application of our multi-faceted mapping strategy permits an increasingly detailed characterization of the genetic networks underlying behavior.

  18. Olfactory classical conditioning in neonatal mouse pups using thermal stimuli.

    Science.gov (United States)

    Bollen, Bieke; Matrot, Boris; Ramanantsoa, Nelina; Van den Bergh, Omer; D'Hooge, Rudi; Gallego, Jorge

    2012-04-01

    Mouse models are increasingly used to investigate genetic contributions to developmental disorders in children, especially newborns. In particular, early cognitive assessment in newborn mice is critical to evaluate pediatric drug efficacy and toxicity. Unfortunately, methods for behavioral tests in newborn mice are scarce. Therefore, developing such tests for newborn mice is a priority challenge for neurogenetics and pharmacological research. The aim of the present study was to develop a conditioning method well suited to high-throughput cognitive screening in newborn mice. To this end, we developed an odor-preference conditioning test using ambient temperature as an unconditioned stimulus (US) and artificial odors as conditioned stimuli (CS). First, we showed that mouse pups move toward the thermoneutral temperature when offered a choice between a thermoneutral and cold environment, thus showing thermotaxis. Second, we conducted a classical conditioning paradigm in pups aged six to ten days. In terms of central nervous system development, this period corresponds to extreme prematurity to early post-term period in humans. During acquisition, the pups were alternatively exposed to odor CS paired with either cold or warm temperatures. Immediately after acquisition, the pups underwent a two-odor choice test, which showed preference for the odor previously paired with the warm temperature, thus showing conditioning. The proposed paradigm is easy to conduct, and requires modest experimenter interference. The method is well suited for high-throughput screening of early associative disorders in newborn mice.

  19. An ERP study of the interaction between verbal information and conditioning pathways to fear.

    Science.gov (United States)

    Ugland, Carina C O; Dyson, Benjamin J; Field, Andy P

    2013-01-01

    Two experiments are described that explore the effects of verbal information and direct conditioning in the acquisition and extinction of fear responses. Participants were given verbal threat information about novel animals before conditioning trials in which the animals were presented alongside an aversive outcome (Experiment 1), or positive information about the animals before extinction trials (Experiment 2). Fear was measured using self-reported fear beliefs, expectancy of the unconditioned stimulus (US) and event-related brain potential (ERP). The results showed a direct effect of verbal information on acquisition (Experiment 1) and extinction (Experiment 2). There was a P2 peak latency shift at acquisition (Experiment 1) and P1 mean amplitude response at extinction (Experiment 2) based on the interaction between verbal information and US-contingency. However, the P2 response showed little evidence for an enhanced conditioned response (CR) when verbal threat information and direct conditioning combined: earlier P2 responses were found for all animals that had been associated with either threat information or the aversive US. Additionally, increase in P1 mean amplitude response (Experiment 2) seemed to stem from the conflict between verbal information and contingency information, rather than the predicted decrease in response where positive information and extinction training were combined. Future studies are suggested that might explore whether attention/arousal modulate the P1 response as a result of such expectation violations.

  20. Eyeblink classical conditioning differentiates normal aging from Alzheimer's disease.

    Science.gov (United States)

    Woodruff-Pak, D S

    2001-01-01

    Eyeblink classical conditioning is a useful paradigm for the study of the neurobiology of learning, memory, and aging, which also has application in the differential diagnosis of neurodegenerative diseases expressed in advancing age. Converging evidence from studies of eyeblink conditioning in neurological patients and brain imaging in normal adults document parallels in the neural substrates of this form of associative learning in humans and non-human mammals. Age differences in the short-delay procedure (400 ms CS-US interval) appear in middle age in humans and may be caused at least in part by cerebellar cortical changes such as loss of Purkinje cells. Whereas the hippocampus is not essential for conditioning in the delay procedure, disruption of hippocampal cholinergic neurotransmission impairs acquisition and slows the rate of learning. Alzheimer's disease (AD) profoundly disrupts the hippocampaL cholinergic system, and patients with AD consistently perform poorly in eyeblink conditioning. We hypothesize that disruption of hippocampal cholinergic pathways in AD in addition to age-associated Purkinje cell loss results in severely impaired eyeblink conditioning. The earliest pathology in AD occurs in entorhinal cortical input to hippocampus, and eyeblink conditioning may detect this early disruption before declarative learning and memory circuits become impaired. A case study is presented in which eyeblink conditioning detected impending dementia six years before changes on other screening tests indicated impairment. Because eyeblink conditioning is simple, non-threatening, and non-invasive, it may become a useful addition to test batteries designed to differentiate normal aging from mild cognitive impairment that progresses to AD and AD from other types of dementia.

  1. Role of the Ventral Medial Prefrontal Cortex in Mediating Behavioral Control-Induced Reduction of Later Conditioned Fear

    Science.gov (United States)

    Baratta, Michael V.; Lucero, Thomas R.; Amat, Jose; Watkins, Linda R.; Maier, Steven F.

    2008-01-01

    A prior experience of behavioral control over a stressor interferes with subsequent Pavlovian fear conditioning, and this effect is dependent on the activation of the ventral medial prefrontal cortex (mPFCv) at the time of the initial experience with control. It is unknown whether mPFCv activity is necessary during fear learning and/or testing for…

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

    Directory of Open Access Journals (Sweden)

    Vargas-Irwin, Cristina

    2010-06-01

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

  3. Post-Weaning, Forebrain-Specific Perturbation of the Oxytocin System Impairs Fear Conditioning

    OpenAIRE

    Pagani, Jerome H.; Lee, Heon-Jin; Young, W. Scott

    2011-01-01

    Oxytocin (Oxt) and vasopressin (Avp) are important for a wide variety of behaviors and the use of transgenic mice lacking the peptides or their receptors, particularly when their loss is spatially and temporally manipulated, offers an opportunity to closely examine their role in a particular behavior. We used a cued fear conditioning paradigm to examine associative learning in three lines of transgenic mice: mice that constitutively lack vasopressin 1a (Avpr1a−/−) or Oxt receptors (Oxtr−/−) a...

  4. Strain-dependent Effects of Acute, Chronic, and Withdrawal from Chronic Nicotine on Fear Conditioning

    OpenAIRE

    Portugal, George S.; Wilkinson, Derek S.; Kenney, Justin W.; Sullivan, Colleen; Gould, Thomas J.

    2011-01-01

    The effects of nicotine on cognitive processes such as learning and memory may play an important role in the addictive liability of tobacco. However, it remains unknown whether genetic variability modulates the effects of nicotine on learning and memory. The present study characterized the effects of acute, chronic, and withdrawal from chronic nicotine administration on fear conditioning, somatic signs, and the elevated plus maze in 8 strains of inbred mice. Strain-dependent effects of acute ...

  5. CLASSICAL CONDITIONING OF THREE KINDS OF HUMOR IN PUBLICITY

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    CAROLINA M. CIFUENTES

    2006-01-01

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

  6. Buchert coarse-graining and the classical energy conditions

    CERN Document Server

    Visser, Matt

    2015-01-01

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

  7. Differential effects of CB1 receptor agonism in behavioural tests of unconditioned and conditioned fear in adult male rats.

    Science.gov (United States)

    Simone, Jonathan J; Green, Matthew R; Hodges, Travis E; McCormick, Cheryl M

    2015-02-15

    We investigated the effects of the highly selective CB1 receptor agonist ACEA and the CB1 receptor antagonist/inverse agonist AM251 on two behavioural tests of unconditioned fear, the elevated plus maze (EPM) and open field test (OFT), as well as on the recall and extinction of a conditioned auditory fear. Both ACEA and AM251 increased anxiety-like behaviour in the EPM and OFT. There was no effect of either drug on recall of the conditioned fear, and ACEA enhanced and AM251 impaired fear extinction. Further, though both the low (0.1 mg/kg) and high (0.5 mg/kg) dose of ACEA facilitated fear extinction, the low dose attenuated, and the high dose potentiated, fear induced corticosterone release suggesting independent effects of the drug on fear and stress responses. Although the extent to which cannabinoids are anxiogenic or anxiolytic has been proposed to be dose-dependent, these results indicate that the same dose has differential effects across tasks, likely based in differences in sensitivities of CB1 receptors to the agonist in the neural regions subserving unconditioned and conditioned fear.

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

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    Rachel eSjouwerman

    2015-12-01

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

  9. Time course of dorsal and ventral hippocampal involvement in the expression of trace fear conditioning.

    Science.gov (United States)

    Cox, David; Czerniawski, Jennifer; Ree, Fredrick; Otto, Tim

    2013-11-01

    While a number of early studies demonstrated that hippocampal damage attenuates the expression of recent, but not remotely trained tasks, an emerging body of evidence has shown that damage to, or inactivation of, the hippocampus often impairs recall across a wide range of training-testing intervals. Collectively, these data suggest that the time course of hippocampal involvement in the storage or recall of previously-acquired memories may differ according to hippocampal subregion and the particular learning task under consideration. The present study examined the contributions of dorsal (DH) and ventral (VH) hippocampus to the expression of previously-acquired trace fear conditioning, a form of Pavlovian conditioning in which the offset of an initially neutral cue or cues and the onset of an aversive stimulus is separated by a temporal (trace) interval. Specifically, either saline or the GABA-A agonist muscimol was infused into DH or VH prior to testing either 1, 7, 28, or 42 days after trace fear conditioning. The results revealed a marked dissociation: pre-testing inactivation of DH failed to impair performance at any time-point, while pre-testing inactivation of VH impaired performance at all time-points. Importantly, pre-testing inactivation of VH had no effect on the performance of previously-acquired delay conditioning, suggesting that the deficits observed in trace conditioning cannot be attributed to a deficit in performance of the freezing response. Collectively, these data suggest that VH, but not DH, remains a neuroanatomical locus critical to the recall or expression of trace fear conditioning over an extended period of time.

  10. Preparing for an Important Event: Demonstrating the Modern View of Classical Conditioning.

    Science.gov (United States)

    Kohn, Art; Kalat, James W.

    1992-01-01

    Explains a simple classroom demonstration of the modern view of classical conditioning. Suggests that the exercise is a useful demonstration of the view that classical conditioning helps prepare an organism for an upcoming event. Argues that the demonstration can show students that classical conditioning is broader and more intriguing than…

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

    Science.gov (United States)

    Bowers, Mallory E; Ressler, Kerry J

    2015-09-01

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

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

    Science.gov (United States)

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

    2014-12-01

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

  13. Classic conditioning in aged rabbits: delay, trace, and long-delay conditioning.

    Science.gov (United States)

    Solomon, P R; Groccia-Ellison, M E

    1996-06-01

    Young (0.5 years) and aged (2+, 3+, and 4+ years) rabbits underwent acquisition of the classically conditioned nictitating membrane response in a delay (500-ms conditioned stimulus [CS], 400-ms interstimulus interval [ISI]), long-delay (1,000-ms CS, 900-ms ISI), or trace (500-ms CS, 400-ms stimulus-free period) paradigm. Collapsing across age groups, there is a general tendency for animals to acquire trace conditioning more slowly than delay conditioning. Collapsing across conditioning paradigms, there is a general tendency for aged animals to acquire more slowly than younger animals. Of greater significance, however, are the age differences in the different conditioning paradigms. In the delay and long-delay paradigms, significant conditioning deficits first appeared in the 4(+)-year-old group. In the trace conditioning paradigm, significant conditioning deficits became apparent in the 2(+)-year-old animals.

  14. Rapid changes in the light/dark cycle disrupt memory of conditioned fear in mice.

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    Dawn H Loh

    Full Text Available BACKGROUND: Circadian rhythms govern many aspects of physiology and behavior including cognitive processes. Components of neural circuits involved in learning and memory, e.g., the amygdala and the hippocampus, exhibit circadian rhythms in gene expression and signaling pathways. The functional significance of these rhythms is still not understood. In the present study, we sought to determine the impact of transiently disrupting the circadian system by shifting the light/dark (LD cycle. Such "jet lag" treatments alter daily rhythms of gene expression that underlie circadian oscillations as well as disrupt the synchrony between the multiple oscillators found within the body. METHODOLOGY/PRINCIPAL FINDINGS: We subjected adult male C57Bl/6 mice to a contextual fear conditioning protocol either before or after acute phase shifts of the LD cycle. As part of this study, we examined the impact of phase advances and phase delays, and the effects of different magnitudes of phase shifts. Under all conditions tested, we found that recall of fear conditioned behavior was specifically affected by the jet lag. We found that phase shifts potentiated the stress-evoked corticosterone response without altering baseline levels of this hormone. The jet lag treatment did not result in overall sleep deprivation, but altered the temporal distribution of sleep. Finally, we found that prior experience of jet lag helps to compensate for the reduced recall due to acute phase shifts. CONCLUSIONS/SIGNIFICANCE: Acute changes to the LD cycle affect the recall of fear-conditioned behavior. This suggests that a synchronized circadian system may be broadly important for normal cognition and that the consolidation of memories may be particularly sensitive to disruptions of circadian timing.

  15. Auditory Cortex is Important in the Extinction of Two Different Tone-Based Conditioned Fear Memories in Rats.

    Science.gov (United States)

    Song, Eun Young; Boatman, Jeffrey A; Jung, Min Whan; Kim, Jeansok J

    2010-01-01

    Extensive fear extinction research is guided by the view that there are structures in the brain that develop inhibitory control over the expression of conditioned fear memories. While the medial prefrontal cortex has recently captured attention as the locus of plasticity essential for extinction of conditioned fear, the auditory cortex is another plausible cortical area involved in extinction learning since it is considered a sufficient conditioned stimulus (CS) pathway in tone fear conditioning. We examined the role of auditory cortex in extinction of auditory-based fear memories with a standard tone-on conditioning, wherein a tone CS predicted a footshock unconditioned stimulus (US), or a novel tone-off conditioning, in which the tone was continually present and the offset of the tone was the CS predicting the US. Rats with bilateral auditory cortex lesions were trained in either paradigm and subsequently trained in extinction to the CS. Auditory cortex lesions had no effect on acquisition but impaired extinction to both CSs. These findings indicate that the auditory cortex contributes to extinction of wide-ranging auditory fear memories, as evidenced by deficits in both tone-on CS and tone-off CS extinction training.

  16. 5-HT7 receptor-mediated fear conditioning and possible involvement of extracellular signal-regulated kinase.

    Science.gov (United States)

    Takeda, Kotaro; Tsuji, Minoru; Miyagawa, Kazuya; Takeda, Hiroshi

    2017-01-18

    Fear conditioning is a valuable behavioral paradigm for studying the neural basis of emotional learning and memory. The present study examined the involvement of extracellular signal-regulated kinase 1/2 (ERK) signaling on the serotonin (5-HT)7 receptor-mediated fear conditioning. Conditioning was performed in a trial in which a tone was followed by an electrical foot-shock. Context- and tone-dependent fear were examined in tests conducted 24 and 48h after conditioning, respectively. The selective 5-HT7 receptor antagonist 2a-[4-(4-phenyl-1,2,3,6-tetrahydropyridyl)butyl]-2a,3,4,-tetrahydrobenzo(c,d)indol-2-(1H)-one (DR4004) (5mg/kg), when administered intraperitoneally (i.p.) immediately after conditioning, caused a significant decrease in both context- and tone-dependent fear responses (freezing behavior). A significant increase in ERK activity was observed in the amygdala of mice that displayed context- or tone-dependent fear responses, and these changes were also inhibited by the administration of DR4004 (5mg/kg, i.p.) immediately after conditioning. In contrast, the increase in hippocampal ERK activity in mice that displayed context-dependent fear responses was further enhanced by the administration of DR4004 (5mg/kg, i.p.). These results suggest that 5-HT7 receptor-mediated ERK signaling may play a significant role in the processes of emotional learning and memory.

  17. Reciprocal Patterns of c-Fos Expression in the Medial Prefrontal Cortex and Amygdala after Extinction and Renewal of Conditioned Fear

    Science.gov (United States)

    Knapska, Ewelina; Maren, Stephen

    2009-01-01

    After extinction of conditioned fear, memory for the conditioning and extinction experiences becomes context dependent. Fear is suppressed in the extinction context, but renews in other contexts. This study characterizes the neural circuitry underlying the context-dependent retrieval of extinguished fear memories using c-Fos immunohistochemistry.…

  18. Systemic or Intra-Amygdala Injection of a Benzodiazepine (Midazolam) Impairs Extinction but Spares Re-Extinction of Conditioned Fear Responses

    Science.gov (United States)

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

    2009-01-01

    Rats were subjected to one or two cycles of fear conditioning and extinction, injected with a benzodiazepine, midazolam, before the first or second extinction, and tested for long-term inhibition of fear responses (freezing). In Experiment 1, inhibition of context-conditioned fear was spared when midazolam was injected before the second…

  19. Eyeblink Classical Conditioning in Alcoholism and Fetal Alcohol Spectrum Disorders.

    Science.gov (United States)

    Cheng, Dominic T; Jacobson, Sandra W; Jacobson, Joseph L; Molteno, Christopher D; Stanton, Mark E; Desmond, John E

    2015-01-01

    Alcoholism is a debilitating disorder that can take a significant toll on health and professional and personal relationships. Excessive alcohol consumption can have a serious impact on both drinkers and developing fetuses, leading to long-term learning impairments. Decades of research in laboratory animals and humans have demonstrated the value of eyeblink classical conditioning (EBC) as a well-characterized model system to study the neural mechanisms underlying associative learning. Behavioral EBC studies in adults with alcohol use disorders and in children with fetal alcohol spectrum disorders report a clear learning deficit in these two patient populations, suggesting alcohol-related damage to the cerebellum and associated structures. Insight into the neural mechanisms underlying these learning impairments has largely stemmed from laboratory animal studies. In this mini-review, we present and discuss exemplary animal findings and data from patient and neuroimaging studies. An improved understanding of the neural mechanisms underlying learning deficits in EBC related to alcoholism and prenatal alcohol exposure has the potential to advance the diagnoses, treatment, and prevention of these and other pediatric and adult disorders.

  20. A risk variant for alcoholism in the NMDA receptor affects amygdala activity during fear conditioning in humans.

    Science.gov (United States)

    Cacciaglia, Raffaele; Nees, Frauke; Pohlack, Sebastian T; Ruttorf, Michaela; Winkelmann, Tobias; Witt, Stephanie H; Nieratschker, Vanessa; Rietschel, Marcella; Flor, Herta

    2013-09-01

    People at high risk for alcoholism show deficits in aversive learning, as indicated by impaired electrodermal responses during fear conditioning, a basic form of associative learning that depends on the amygdala. A positive family history of alcohol dependence has also been related to decreased amygdala responses during emotional processing. In the present study we report reduced amygdala activity during the acquisition of conditioned fear in healthy carriers of a risk variant for alcoholism (rs2072450) in the NR2A subunit-containing N-methyl-d-aspartate (NMDA)-receptor. These results indicate that rs2072450 might confer risk for alcohol dependence through deficient fear acquisition indexed by a diminished amygdala response during aversive learning, and provide a neural basis for a weak behavioral inhibition previously documented in individuals at high risk for alcohol dependence. Carriers of the risk variant additionally exhibit dampened insula activation, a finding that further strengthens our data, given the importance of this brain region in fear conditioning.

  1. Differential roles of the basolateral amygdala and nucleus basalis magnocellularis during post-reactivation contextual fear conditioning reconsolidation in rats.

    Science.gov (United States)

    Baldi, Elisabetta; Mariottini, Chiara; Bucherelli, Corrado

    2008-11-01

    The roles of the basolateral amygdala and nucleus basalis magnocellularis in fear conditioning reconsolidation were investigated by means of tetrodotoxin bilateral inactivation performed 96 h after conditioning, immediately after reactivation training. Footshocks of 1.2 mA intensity were employed to induce the generalization phenomenon. Basolateral amygdala inactivation disrupts the contextual fear response and its generalization but not acoustic CS trace retention, when measured 72 and 96 h after tetrodotoxin administration. Nucleus basalis magnocellularis functional inactivation does not affect memory post-reactivation phase of any of the three conditioned fear responses. The present findings show a differential role of the two structures in fear memory reconsolidation and can be a starting point for future investigation of the neural circuits subserving generalization.

  2. Fimbria-fornix and entorhinal cortex differential contribution to contextual and cued fear conditioning consolidation in rats.

    Science.gov (United States)

    Baldi, Elisabetta; Liuzzo, Antonino; Bucherelli, Corrado

    2013-04-10

    The Fimbria-Fornix (FF) and Entorhinal Cortex (EC) are the primary interfaces between the hippocampus and, respectively, subcortical structures and cortical areas. Their mnemonic role has been repeatedly proposed. In order to investigate their role in fear conditioning, FF and EC were subjected to bilateral fully reversible tetrodotoxin (TTX) inactivation during consolidation in adult male Wistar rats that had undergone training for fear conditioning to an acoustic stimulus (CS) and context. TTX was stereotaxically injected into animals of different groups at increasing post-acquisition delays. Memory was assessed as conditioned freezing duration measured during retention testing, performed 72 and 96 h after TTX administration in a counterbalanced manner. The results showed that FF inactivation, performed immediately after conditioning, did not disrupt consolidation of either contextual or auditory fear memory. On the contrary, EC inactivation performed at the same time was followed by both contextual and CS fear response retention impairment. EC inactivation performed 1.5h post-acquisition impaired only contextual fear response retention. EC inactivation performed 24h after acquisition training had no effect on the consolidation process. The present findings show a clearly different role of FF and EC in fear conditioning consolidation in the rat. The results are discussed in relation to their known connections with the hippocampus.

  3. Do panic patients process unconditioned fear vs. conditioned anxiety differently than normal subjects?

    Science.gov (United States)

    Del-Ben, C M; Vilela, J A; Hetem, L A; Guimarães, F S; Graeff, F G; Zuardi, A W

    2001-11-30

    Panic patients were evaluated with two models of experimental anxiety that are believed to generate distinct emotional states: (1) a stimulated public speaking test (SPS), a presumed indicator of unconditioned fear, and (2) conditioning of skin conductance responses (CSCR) to a tone associated with an aversive white noise, an index of conditioned anxiety. Subjective states were evaluated through the visual analogue mood scale (VAMS) and a bodily symptoms scale (BSS). In the SPS test, panic patients showed higher baseline levels of VAMS-measured anxiety than controls. Unlike controls, panic patients failed to show increased anxiety before and during speech. Although baseline levels of arousal were similar in both groups, VAMS mental sedation decreased in controls, but not in panic patients during the SPS. Panic patients showed more discontent than controls throughout the whole experimental session. They also scored higher than controls on several items of the BSS. In the CSCR test, panic patients showed more spontaneous fluctuations of skin conductance than controls. Nevertheless, conditioning of skin conductance responses to the tone was similar in both groups. Therefore, panic patients seemed to process unconditioned fear abnormally.

  4. Cannabinoid modulation of chronic mild stress-induced selective enhancement of trace fear conditioning in adolescent rats.

    Science.gov (United States)

    Reich, Christian G; Iskander, Anthony N; Weiss, Michael S

    2013-10-01

    History of stress is considered a major risk factor for the development of major depression and posttraumatic stress disorder (PTSD). Elucidating the neurobiological mechanisms of Pavlovian fear conditioning may provide insight into the etiology of PTSD. In the current study, adolescent male Sprague-Dawley rats were exposed to 3 weeks of a chronic-mild-unpredictable stress (CMS) protocol. Immediately following the CMS, the animals were subjected to hippocampal-dependent (trace and contextual) and hippocampal-independent (delay) fear conditioning. CMS exposure enhanced trace freezing behavior compared to non-stress controls. This effect was not observed in contextual or delay conditioned animals. Given that the endocannabinoid system is negatively affected by CMS procedures, separate groups of stressed rats were administered the CB1 receptor agonist, ACEA (0.1 mg/kg), prior to trace fear conditioning or a memory-recall test. Regardless of administration time, ACEA significantly reduced freezing behavior in stressed animals. Furthermore, when administered during the first memory recall test, ACEA enhanced long-term extinction in both stress and non-stress groups. The results demonstrate that chronic unpredictable stress selectively enhances hippocampal-dependent episodic fear memories. Pathologies of the episodic memory and fear response may increase the susceptibility of developing PTSD. Reduction in fear responses via exogenous activation of the CB1 receptor suggests that a deficiency in the endocannabinoid system contributes to this pathology.

  5. Fear-potentiated startle processing in humans: Parallel fMRI and orbicularis EMG assessment during cue conditioning and extinction.

    Science.gov (United States)

    Lindner, Katja; Neubert, Jörg; Pfannmöller, Jörg; Lotze, Martin; Hamm, Alfons O; Wendt, Julia

    2015-12-01

    Studying neural networks and behavioral indices such as potentiated startle responses during fear conditioning has a long tradition in both animal and human research. However, most of the studies in humans do not link startle potentiation and neural activity during fear acquisition and extinction. Therefore, we examined startle blink responses measured with electromyography (EMG) and brain activity measured with functional MRI simultaneously during differential conditioning. Furthermore, we combined these behavioral fear indices with brain network activity by analyzing the brain activity evoked by the startle probe stimulus presented during conditioned visual threat and safety cues as well as in the absence of visual stimulation. In line with previous research, we found a fear-induced potentiation of the startle blink responses when elicited during a conditioned threat stimulus and a rapid decline of amygdala activity after an initial differentiation of threat and safety cues in early acquisition trials. Increased activation during processing of threat cues was also found in the anterior insula, the anterior cingulate cortex (ACC), and the periaqueductal gray (PAG). More importantly, our results depict an increase of brain activity to probes presented during threatening in comparison to safety cues indicating an involvement of the anterior insula, the ACC, the thalamus, and the PAG in fear-potentiated startle processing during early extinction trials. Our study underlines that parallel assessment of fear-potentiated startle in fMRI paradigms can provide a helpful method to investigate common and distinct processing pathways in humans and animals and, thus, contributes to translational research.

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

    Directory of Open Access Journals (Sweden)

    Jonathan P Fadok

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

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

    Science.gov (United States)

    Hunter, Amy Silvestri

    2015-07-01

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

  8. Reinstatement of Extinguished Conditioned Responses and Negative Stimulus Valence as a Pathway to Return of Fear in Humans

    Science.gov (United States)

    Dirikx, Trinette; Hermans, Dirk; Vansteenwegen, Debora; Baeyens, Frank; Eelen, Paul

    2004-01-01

    The present study investigated reinstatement of conditioned responses in humans by using a differential Pavlovian conditioning procedure. Evidence for reinstatement was established in a direct (fear rating) and in an indirect measure (secondary reaction time task) of conditioning. Moreover, the amount of reinstatement in the secondary reaction…

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

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    Woods, Amanda M.; Bouton, Mark E.

    2008-01-01

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

  10. Pre-Training Reversible Inactivation of the Basal Amygdala (BA Disrupts Contextual, but Not Auditory, Fear Conditioning, in Rats.

    Directory of Open Access Journals (Sweden)

    Elisa Mari Akagi Jordão

    Full Text Available The basolateral amygdala complex (BLA, including the lateral (LA, basal (BA and accessory basal (AB nuclei, is involved in acquisition of contextual and auditory fear conditioning. The BA is one of the main targets for hippocampal information, a brain structure critical for contextual learning, which integrates several discrete stimuli into a single configural representation. Congruent with the hodology, selective neurotoxic damage to the BA results in impairments in contextual, but not auditory, fear conditioning, similarly to the behavioral impairments found after hippocampal damage. This study evaluated the effects of muscimol-induced reversible inactivation of the BA during a simultaneous contextual and auditory fear conditioning training on later fear responses to both the context and the tone, tested separately, without muscimol administration. As compared to control rats micro-infused with vehicle, subjects micro-infused with muscimol before training exhibited, during testing without muscimol, significant reduction of freezing responses to the conditioned context, but not to the conditioned tone. Therefore, reversible inactivation of the BA during training impaired contextual, but not auditory fear conditioning, thus confirming and extending similar behavioral observations following selective neurotoxic damage to the BA and, in addition, revealing that this effect is not related to the lack of a functional BA during testing.

  11. A pragmatic comparison of noise burst and electric shock unconditioned stimuli for fear conditioning research with many trials.

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    Sperl, Matthias F J; Panitz, Christian; Hermann, Christiane; Mueller, Erik M

    2016-09-01

    Several methods that are promising for studying the neurophysiology of fear conditioning (e.g., EEG, MEG) require a high number of trials to achieve an adequate signal-to-noise ratio. While electric shock and white noise burst are among the most commonly used unconditioned stimuli (US) in conventional fear conditioning studies with few trials, it is unknown whether these stimuli are equally well suited for paradigms with many trials. Here, N = 32 participants underwent a 260-trial differential fear conditioning and extinction paradigm with a 240-trial recall test 24 h later and neutral faces as conditioned stimuli. In a between-subjects design, either white noise bursts (n = 16) or electric shocks (n = 16) served as US, and intensities were determined using the most common procedure for each US (i.e., a fixed 95 dB noise burst and a work-up procedure for electric shocks, respectively). In addition to differing US types, groups also differed in closely linked US-associated characteristics (e.g., calibration methods, stimulus intensities, timing). Subjective ratings (arousal/valence), skin conductance, and evoked heart period changes (i.e., fear bradycardia) indicated more reliable, extinction-resistant, and stable conditioning in the white noise burst versus electric shock group. In fear conditioning experiments where many trials are presented, white noise burst should serve as US.

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

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    Jun-Li Liu

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

  13. Investigating the impact of sex and cortisol on implicit fear conditioning with fMRI.

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    Merz, Christian J; Tabbert, Katharina; Schweckendiek, Jan; Klucken, Tim; Vaitl, Dieter; Stark, Rudolf; Wolf, Oliver T

    2010-01-01

    Fear conditioning is influenced by stress but opposing effects in males and females have often been reported. In a previous human functional magnetic resonance imaging (fMRI) study, we observed acute effects of the stress hormone cortisol on prefrontal structures. Men showed evidence for impaired fear conditioning after cortisol treatment, while the opposite pattern was found for women. In the current experiment, we tested whether similar sex-dependent effects would occur on the neural level if contingency awareness was prevented experimentally to investigate implicit learning processes. A differential fear conditioning experiment with transcutaneous electrical stimulation as unconditioned stimulus and geometric figures as conditioned stimuli (CS) was conducted. One figure was always paired (CS+), whereas the other (CS-) was never paired with the UCS. Thirty-nine (19 female) subjects participated in this fMRI study, receiving either placebo or 30 mg cortisol (hydrocortisone) before conditioning. Dependent variables were skin conductance responses (SCRs) and neural activity (BOLD signal). In line with prior findings in unaware participants, no differential learning could be observed for the SCRs. However, a sex x cortisol interaction was detected with a reduced mean response to the CS after cortisol treatment in men, while the opposite pattern was observed in women (enhanced mean SCR under cortisol). In the contrast CS+ minus CS-, neural activity showed a sex x cortisol interaction in the insula and further trends in the hippocampus and the thalamus. In these regions, cortisol reduced the CS+/CS- differentiation in men but enhanced it in women. In contrast to these sex specific effects, differential amygdala activation was found in the placebo group but not in the cortisol group, irrespective of sex. Further, differential neural activity in the amygdala and thalamus were positively correlated with the SCRs in the placebo group only. The present study in contingency

  14. Acute Cognitive Impairment After Lateral Fluid Percussion Brain Injury Recovers by One Month: Evaluation by Conditioned Fear Response

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    Lifshitz, Jonathan; Witgen, Brent M.; Grady, M. Sean

    2007-01-01

    Conditioned fear associates a contextual environment and cue stimulus to a foot shock in a single training trial, where fear expressed to the trained context or cue indicates cognitive performance. Lesion, aspiration or inactivation of the hippocampus and amygdala impair conditioned fear to the trained context and cue, respectively. Moreover, only bilateral experimental manipulations, in contrast to unilateral, abolish cognitive performance. In a model of unilateral brain injury, we sought to test whether a single lateral fluid percussion brain injury impairs cognitive performance in conditioned fear. Brain-injured mice were evaluated for anterograde cognitive deficits, with the hypothesis that acute injury-induced impairments improve over time. Male C57BL/6J mice were brain-injured, trained at five or 27 days post-injury, and tested 48 hours later for recall of the association between the conditioned stimuli (trained context or cue) and the unconditioned stimulus (foot shock) by quantifying fear-associated freezing behavior. A significant anterograde hippocampal-dependent cognitive deficit was observed at seven days in brain-injured compared to sham. Cued fear conditioning could not detect amygdala-dependent cognitive deficits after injury and stereological estimation of amygdala neuron number corroborated this finding. The absence of injury-related freezing in a novel context substantiated injury-induced hippocampal-dependent cognitive dysfunction, rather than generalized fear. Variations in the training and testing paradigms demonstrated a cognitive deficit in consolidation, rather than acquisition or recall. By one month post-injury, cognitive function recovered in brain-injured mice. Hence, the acute injury-induced cognitive impairment may persist while transient pathophysiological sequelae are underway, and improve as global dysfunction subsides. PMID:17169443

  15. Acute cognitive impairment after lateral fluid percussion brain injury recovers by 1 month: evaluation by conditioned fear response.

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    Lifshitz, Jonathan; Witgen, Brent M; Grady, M Sean

    2007-02-27

    Conditioned fear associates a contextual environment and cue stimulus to a foot shock in a single training trial, where fear expressed to the trained context or cue indicates cognitive performance. Lesion, aspiration or inactivation of the hippocampus and amygdala impair conditioned fear to the trained context and cue, respectively. Moreover, only bilateral experimental manipulations, in contrast to unilateral, abolish cognitive performance. In a model of unilateral brain injury, we sought to test whether a single lateral fluid percussion brain injury impairs cognitive performance in conditioned fear. Brain-injured mice were evaluated for anterograde cognitive deficits, with the hypothesis that acute injury-induced impairments improve over time. Male C57BL/6J mice were brain-injured, trained at 5 or 27 days post-injury, and tested 48h later for recall of the association between the conditioned stimuli (trained context or cue) and the unconditioned stimulus (foot shock) by quantifying fear-associated freezing behavior. A significant anterograde hippocampal-dependent cognitive deficit was observed at 7 days in brain-injured compared to sham. Cued fear conditioning could not detect amygdala-dependent cognitive deficits after injury and stereological estimation of amygdala neuron number corroborated this finding. The absence of injury-related freezing in a novel context substantiated injury-induced hippocampal-dependent cognitive dysfunction, rather than generalized fear. Variations in the training and testing paradigms demonstrated a cognitive deficit in consolidation, rather than acquisition or recall. By 1-month post-injury, cognitive function recovered in brain-injured mice. Hence, the acute injury-induced cognitive impairment may persist while transient pathophysiological sequelae are underway, and improve as global dysfunction subsides.

  16. Maladaptive behavioral consequences of conditioned fear-generalization: a pronounced, yet sparsely studied, feature of anxiety pathology.

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    van Meurs, Brian; Wiggert, Nicole; Wicker, Isaac; Lissek, Shmuel

    2014-06-01

    Fear-conditioning experiments in the anxiety disorders focus almost exclusively on passive-emotional, Pavlovian conditioning, rather than active-behavioral, instrumental conditioning. Paradigms eliciting both types of conditioning are needed to study maladaptive, instrumental behaviors resulting from Pavlovian abnormalities found in clinical anxiety. One such Pavlovian abnormality is generalization of fear from a conditioned danger-cue (CS+) to resembling stimuli. Though lab-based findings repeatedly link overgeneralized Pavlovian-fear to clinical anxiety, no study assesses the degree to which Pavlovian overgeneralization corresponds with maladaptive, overgeneralized instrumental-avoidance. The current effort fills this gap by validating a novel fear-potentiated startle paradigm including Pavlovian and instrumental components. The paradigm is embedded in a computer game during which shapes appear on the screen. One shape paired with electric-shock serves as CS+, and other resembling shapes, presented in the absence of shock, serve as generalization stimuli (GSs). During the game, participants choose whether to behaviorally avoid shock at the cost of poorer performance. Avoidance during CS+ is considered adaptive because shock is a real possibility. By contrast, avoidance during GSs is considered maladaptive because shock is not a realistic prospect and thus unnecessarily compromises performance. Results indicate significant Pavlovian-instrumental relations, with greater generalization of Pavlovian fear associated with overgeneralization of maladaptive instrumental-avoidance.

  17. Activation of ERK/MAP kinase in the amygdala is required for memory consolidation of pavlovian fear conditioning.

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    Schafe, G E; Atkins, C M; Swank, M W; Bauer, E P; Sweatt, J D; LeDoux, J E

    2000-11-01

    Although much has been learned about the neurobiological mechanisms underlying Pavlovian fear conditioning at the systems and cellular levels, relatively little is known about the molecular mechanisms underlying fear memory consolidation. The present experiments evaluated the role of the extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) signaling cascade in the amygdala during Pavlovian fear conditioning. We first show that ERK/MAPK is transiently activated-phosphorylated in the amygdala, specifically the lateral nucleus (LA), at 60 min, but not 15, 30, or 180 min, after conditioning, and that this activation is attributable to paired presentations of tone and shock rather than to nonassociative auditory stimulation, foot shock sensitization, or unpaired tone-shock presentations. We next show that infusions of U0126, an inhibitor of ERK/MAPK activation, aimed at the LA, dose-dependently impair long-term memory of Pavlovian fear conditioning but leaves short-term memory intact. Finally, we show that bath application of U0126 impairs long-term potentiation in the LA in vitro. Collectively, these results demonstrate that ERK/MAPK activation is necessary for both memory consolidation of Pavlovian fear conditioning and synaptic plasticity in the amygdala.

  18. Inactivation of the central nucleus of the amygdala blocks classical conditioning but not conditioning-specific reflex modification of rabbit heart rate.

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    Burhans, Lauren B; Schreurs, Bernard G

    2013-02-01

    Heart rate (HR) conditioning in rabbits is a widely used model of classical conditioning of autonomic responding that is noted for being similar to the development of conditioned heart rate slowing (bradycardia) in humans. We have shown previously that in addition to HR changes to a tone conditioned stimulus (CS), the HR reflex itself can undergo associative change called conditioning-specific reflex modification (CRM) that manifests when tested in the absence of the CS. Because CRM resembles the conditioned bradycardic response to the CS, we sought to determine if HR conditioning and CRM share a common neural substrate. The central nucleus of the amygdala (CeA) is a critical part of the pathway through which conditioned bradycardia is established. To test whether the CeA is also involved in the acquisition and/or expression of CRM, we inactivated the CeA with muscimol during HR conditioning or CRM testing. CeA inactivation blocked HR conditioning without completely preventing CRM acquisition or expression. These results suggest that the CeA may therefore only play a modulatory role in CRM. Theories on the biological significance of conditioned bradycardia suggest that it may represent a state of hypervigilance that facilitates the detection of new and changing contingencies in the environment. We relate these ideas to our results and discuss how they may be relevant to the hypersensitivity observed in fear conditioning disorders like post-traumatic stress.

  19. A Classical Conditioning Procedure for the Hearing Assessment of Multiply Handicapped Persons.

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    Lancioni, Giulio E.; And Others

    1989-01-01

    Hearing assessments of multiply handicapped children/adolescents were conducted using classical conditioning (with an air puff as unconditioned stimulus) and operant conditioning (with a modified visual reinforcement audiometry procedure or edible reinforcement). Findings indicate that classical conditioning was successful with 21 of the 23…

  20. Exploratory studies of classical conditioning of the preoral cavity in harnessed carpenter ants (Camponotus pennsylvanicus).

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    Sauer, Dustin L; Abramson, Charles I; Lawson, Adam L

    2002-06-01

    An attempt was made to classically condition the mouthparts of harnessed worker ants (Camponotus pennsylvanicus) in anticipation of feeding. Experiments were designed to investigate classical conditioning with one CS, discrimination between two CSs, and pseudoconditioning. Analysis indicated a small acquisition effect that could be accounted for by pseudoconditioning. The preparation can be used to study nonassociative learning and some instrumental conditioning situations.

  1. Extending In Vitro Conditioning in "Aplysia" to Analyze Operant and Classical Processes in the Same Preparation

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    Brembs, Bjorn; Baxter, Douglas A.; Byrne, John H.

    2004-01-01

    Operant and classical conditioning are major processes shaping behavioral responses in all animals. Although the understanding of the mechanisms of classical conditioning has expanded significantly, the understanding of the mechanisms of operant conditioning is more limited. Recent developments in "Aplysia" are helping to narrow the gap in the…

  2. Differences in extinction of conditioned fear in C57BL/6 substrains are unrelated to expression of alpha-synuclein.

    Science.gov (United States)

    Siegmund, Anja; Langnaese, Kristina; Wotjak, Carsten T

    2005-02-28

    C57BL/6 mice are commonly used as background strains for genetically modified mice, and little attention is usually paid to the notification of the specific substrain. However, it is known that C57BL/6NCrl (B6N) and C57BL/6JOlaHsd (B6JOla) mice differ in the course of extinction of conditioned fear (Stiedl O, Radulovic J, Lohmann R, Birkenfeld K, Palve M, Kammermeier J, et al. Strain and substrain differences in context- and tone-dependent fear conditioning of inbred mice. Behav Brain Res 1999;104:1-12), as well as in the expression of alpha-synuclein (Specht CG, Schoepfer R. Deletion of the alpha-synuclein locus in a subpopulation of C57BL/6J inbred mice. BMC Neurosci 2001;2:11). We tested for a causal relationship between the two findings by employing B6N (expressing alpha-synuclein), B6JOla (not expressing alpha-syn) and the third strain C57BL/6JCrl (B6Jax, expressing alpha-syn). We show that alpha-syn does not account for differences in extinction in a fear conditioning task, as its expression did not covary with the decrease of freezing on repeated non-reinforced tone and context exposure in the three strains: B6Jax exhibited fastest extinction followed by B6JOla. In contrast, B6N showed persistent fear over the course of extinction training. The differences in extinction between B6JOla and B6N were unrelated to sensorimotor processing (pain threshold and basal tone reaction) and innate fear (light-dark test). However, B6Jax displayed less innate fear than B6JOla and B6N. Our results of marked differences in innate and conditioned fear in three B6 substrains illustrate the necessity of a strict adherence to an exact mouse strain nomenclature.

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

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    Herry, Cyril; Johansen, Joshua P

    2014-12-01

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

  4. Effect of the NMDA antagonist MK-801 on latent inhibition of fear conditioning.

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    Traverso, Luis M; Ruiz, Gabriel; De la Casa, Luis G

    2012-10-01

    N-methyl-D-aspartate (NMDA) receptors seem to play a central role in learning and memory processes involved in Latent Inhibition (LI). In fact, MK-801, a non-competitive NMDA receptor antagonist, has proved its effectiveness as a drug for attenuating LI when administered before or after stimulus preexposure and conditioning stages. This paper presents three experiments designed to analyze the effect of MK-801 on LI when the drug is administered before (Experiment 1A) or after (Experiment 1B) preexposure and conditioning stages with a conditioned emotional response procedure. Additionally, we analyze the effect of the drug when it was administered before preexposure, before conditioning or before both phases (Experiment 2). The results show that the effect of the drug varied as a function of the dose (with only the highest dose being effective), the moment of administration (with only the drug administered before the experimental treatments being effective), and the phase of procedure (reducing LI when the drug was administered only at preexposure, and disrupting fear conditioning when administered at conditioning). These differences may be due to several factors ranging from the role played by NMDA receptors in the processing of stimuli of different sensorial modalities to the molecular processes triggered by drug administration.

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

    Science.gov (United States)

    Broadwater, Margaret A.

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

  6. Fear conditioning and early life vulnerabilities: two distinct pathways of emotional dysregulation and brain dysfunction in PTSD

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    Ruth A. Lanius

    2010-12-01

    Full Text Available The newly proposed criteria for posttraumatic stress disorder (PTSD in the Diagnostic and Statistical Manual (DSM-V include dysregulation of a variety of emotional states including fear, anger, guilt, and shame, in addition to dissociation and numbing. Consistent with these revisions, we postulate two models of emotion dysregulation in PTSD in which fear is not the prevailing emotion but is only one of several components implicated in a dysregulated emotional system that also mediates problems regulating anger, guilt, shame, dissociation, and numbing.We discuss whether there is a relationship between fear and other emotion regulation systems that may help further our understanding of PTSD and its underlying neurocircuitry. Two pathways describing the relationship between fear and other emotion regulation systems in PTSD are proposed. The first pathway describes emotion dysregulation as an outcome of fear conditioning through stress sensitization and kindling. The second pathway views emotion dysregulation as a distal vulnerability factor and hypothesizes a further exacerbation of fear and other emotion regulatory problems, including the development of PTSD after exposure to one or several traumatic event(s later in life. Future research and treatment implications are discussed.

  7. Cholinergic modulation of Pavlovian fear conditioning in rats: differential effects of intrahippocampal infusion of mecamylamine and methyllycaconitine.

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    Vago, David R; Kesner, Raymond P

    2007-03-01

    The cholinergic system has consistently been implicated in Pavlovian fear conditioning. Considerable work has been done to localize specific nicotinic receptor subtypes in the hippocampus and determine their functional importance; however, the specific function of many of these subtypes has yet to be determined. An alpha7 nicotinic antagonist methyllycaconitine (MLA) (35 microg), and a broad spectrum non-alpha7 nicotinic antagonist mecamylamine (35 microg) was injected directly into the dorsal hippocampus or overlying cortex either 15 min pre-, 1 min post-, or 6h post-fear conditioning. One week after conditioning, retention of contextual and cue (tone) conditioning were assessed. A significant impairment in retention of contextual fear was observed when mecamylamine was injected 15 min pre- and 1 min post-conditioning. No significant impairment was observed when mecamylamine was injected 6h post-conditioning. Likewise, a significant impairment in retention of contextual fear was observed when MLA was injected 1 min post-conditioning; however, in contrast, MLA did not show any significant impairments when injected 15 min pre-conditioning, but did show a significant impairment when injected 6h post-conditioning. There were no significant impairments observed when either drug was injected into overlying cortex. No significant impairments were observed in cue conditioning for either drug. In general, specific temporal dynamics involved in nicotinic receptor function were found relative to time of receptor dysfunction. The results indicate that the greatest deficits in long-term retention (1 week) of contextual fear are produced by central infusion of MLA minutes to hours post-conditioning or mecamylamine within minutes of conditioning.

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

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

    2010-01-01

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

  9. Effect of circadian phase on memory acquisition and recall: operant conditioning vs. classical conditioning.

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    Madeleine V Garren

    Full Text Available There have been several studies on the role of circadian clocks in the regulation of associative learning and memory processes in both vertebrate and invertebrate species. The results have been quite variable and at present it is unclear to what extent the variability observed reflects species differences or differences in methodology. Previous results have shown that following differential classical conditioning in the cockroach, Rhyparobia maderae, in an olfactory discrimination task, formation of the short-term and long-term memory is under strict circadian control. In contrast, there appeared to be no circadian regulation of the ability to recall established memories. In the present study, we show that following operant conditioning of the same species in a very similar olfactory discrimination task, there is no impact of the circadian system on either short-term or long-term memory formation. On the other hand, ability to recall established memories is strongly tied to the circadian phase of training. On the basis of these data and those previously reported for phylogenetically diverse species, it is suggested that there may be fundamental differences in the way the circadian system regulates learning and memory in classical and operant conditioning.

  10. Unconscious classical conditioning of sexual arousal: Evidence for the conditioning of female genital arousal to subliminally presented sexual stimuli

    NARCIS (Netherlands)

    S. Both; M. Spiering; E. Laan; S. Balcome; B. van den Heuvel; W. Everaerd

    2008-01-01

    Introduction. Although the assumption that sexual behavior is at least partly learned is common across theories of sexual behavior, classical conditioning of sexual response in women has been seldom studied. Aim. The study of unconscious classical conditioning of appetitive sexual responses in women

  11. Dietary-induced obesity disrupts trace fear conditioning and decreases hippocampal reelin expression.

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    Reichelt, Amy C; Maniam, Jayanthi; Westbrook, R Frederick; Morris, Margaret J

    2015-01-01

    Both obesity and over-consumption of palatable high fat/high sugar "cafeteria" diets in rats has been shown to induce cognitive deficits in executive function, attention and spatial memory. Adult male Sprague-Dawley rats were fed a diet that supplemented standard lab chow with a range of palatable foods eaten by people for 8 weeks, or regular lab chow. Memory was assessed using a trace fear conditioning procedure, whereby a conditioned stimulus (CS) is presented for 10s and then 30s after its termination a foot shock (US) is delivered. We assessed freezing to the CS (flashing light) in a neutral context, and freezing in the context associated with footshock. A dissociation was observed between levels of freezing in the context and to the CS associated with footshock. Cafeteria diet fed rats froze less than control chow fed rats in the context associated with footshock (P<0.01), indicating that encoding of a hippocampus-dependent context representation was impaired in these rats. Conversely, cafeteria diet fed rats froze more (P<0.05) to the CS than chow fed rats, suggesting that when hippocampal function was compromised the cue was the best predictor of footshock, as contextual information was not encoded. Dorsal hippocampal mRNA expression of inflammatory and neuroplasticity markers was analysed at the end of the experiment, 10 weeks of diet. Of these, mRNA expression of reelin, which is known to be important in long term potentiation and neuronal plasticity, was significantly reduced in cafeteria diet fed rats (P=0.003). This implicates reductions in hippocampal plasticity in the contextual fear memory deficits seen in the cafeteria diet fed rats.

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

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    Evans S

    2013-03-01

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

  13. Effects of sleep deprivation on different phases of memory in the rat: dissociation between contextual and tone fear conditioning tasks

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    Vanessa C Rossi

    2014-11-01

    Full Text Available Numerous studies show that sleep deprivation (SD impacts negatively on cognitive processes, including learning and memory. Memory formation encompasses distinct phases of which acquisition, consolidation and retrieval are better known. Previous studies with pre-training SD induced by the platform method have shown impairment in fear conditioning tasks. Nonetheless, pre-training manipulations do not allow the distinction between effects on acquisition and/or consolidation, interfering, ultimately, on recall of/performance in the task. In the present study, animals were first trained in contextual and tone fear conditioning tasks and then submitted to SD with the purpose to evaluate the effect of this manipulation on different stages of the learning process, e.g. in the uptake of (new information during learning, its encoding and stabilization, and the recall of stored memories. Besides, we also investigated the effect of SD in the extinction of fear memory and a possible state-dependent learning induced by this manipulation. For each task (contextual or tone fear conditioning, animals were trained and then distributed into control, not sleep-deprived (CTL and SD groups, the latter being submitted to the modified multiple platform paradigm for 96 h. Subsets of eight rats in each group/experiment were submitted to the test of the tasks, either immediately or at different time intervals after SD. The results indicated that a pre-, but not post-training SD impaired recall in the contextual and tone fear conditioning; b this impairment was not state-dependent; c in the contextual fear conditioning, pre-test SD prevented extinction of the learned task. Overall, these results suggest that SD interferes with acquisition, recall and extinction, but not necessarily with consolidation of emotional memory.

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

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    Julie eBoulanger Bertolus

    2014-05-01

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

  15. Hemodynamic responses in amygdala and hippocampus distinguish between aversive and neutral cues during Pavlovian fear conditioning in behaving rats.

    Science.gov (United States)

    McHugh, Stephen B; Marques-Smith, Andre; Li, Jennifer; Rawlins, J N P; Lowry, John; Conway, Michael; Gilmour, Gary; Tricklebank, Mark; Bannerman, David M

    2013-02-01

    Lesion and electrophysiological studies in rodents have identified the amygdala and hippocampus (HPC) as key structures for Pavlovian fear conditioning, but human functional neuroimaging studies have not consistently found activation of these structures. This could be because hemodynamic responses cannot detect the sparse neuronal activity proposed to underlie conditioned fear. Alternatively, differences in experimental design or fear levels could account for the discrepant findings between rodents and humans. To help distinguish between these alternatives, we used tissue oxygen amperometry to record hemodynamic responses from the basolateral amygdala (BLA), dorsal HPC (dHPC) and ventral HPC (vHPC) in freely-moving rats during the acquisition and extinction of conditioned fear. To enable specific comparison with human studies we used a discriminative paradigm, with one auditory cue [conditioned stimulus (CS)+] that was always followed by footshock, and another auditory cue (CS-) that was never followed by footshock. BLA tissue oxygen signals were significantly higher during CS+ than CS- trials during training and early extinction. In contrast, they were lower during CS+ than CS- trials by the end of extinction. dHPC and vHPC tissue oxygen signals were significantly lower during CS+ than CS- trials throughout extinction. Thus, hemodynamic signals in the amygdala and HPC can detect the different patterns of neuronal activity evoked by threatening vs. neutral stimuli during fear conditioning. Discrepant neuroimaging findings may be due to differences in experimental design and/or fear levels evoked in participants. Our methodology offers a way to improve translation between rodent models and human neuroimaging.

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

    Directory of Open Access Journals (Sweden)

    Tim eKlucken

    2015-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Benjamin N Greenwood

    2014-10-01

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

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

    OpenAIRE

    Woods, Amanda M.; Bouton, Mark E.

    2008-01-01

    Five experiments with rat subjects compared the effects of immediate and delayed extinction on the durability of extinction learning. Three experiments examined extinction of fear conditioning (using the conditioned emotional response method), and two experiments examined extinction of appetitive conditioning (using the food-cup entry method). In all experiments, conditioning and extinction were accomplished in single sessions, and retention testing took place 24 h after extinction. In both f...

  19. Using powerpoint to demonstrate human classical salivary conditioning in a classroom situation.

    Science.gov (United States)

    Abramson, Charles I; Brown, Erika A; Langley, Dillon

    2011-02-01

    Classical conditioning is one of the most fundamental types of learning, yet demonstrating its principles in a classroom setting can be challenging. This study introduces using PowerPoint as a new, practical technique that can be used in a classroom setting to demonstrate classical conditioning. The PowerPoint file is flexible and easy to adapt for demonstrating various aspects of classical conditioning (including higher order conditioning) in a concrete manner. Moreover, this study was designed to measure salivation in a more objective and valid way which could be used by student researchers interested in measuring salivation as a conditioned response.

  20. Demonstrating Classical Conditioning in Introductory Psychology: Needles Do Not Always Make Balloons Pop!

    Science.gov (United States)

    Vernoy, Mark W.

    1987-01-01

    Describes a method of teaching classical conditioning to an introductory psychology class which involves demonstrating the conditioned response that occurs when a needle pierces, but does not pop, a balloon. (GEA)

  1. Fast, transient cardiac accelerations and decelerations during fear conditioning in rats.

    Science.gov (United States)

    Knippenberg, J M J; Barry, R J; Kuniecki, M J; van Luijtelaar, G

    2012-02-01

    The current study reports on a number of heart rate responses observed in rats subjected to a discriminatory Pavlovian fear conditioning procedure. Rats learned that a series of six auditory pips was followed by a footshock when presented alone, but not when the pip series was preceded by a visual safety signal. Each auditory pip in the series evoked a fast transient (transient decelerations are similar to the human Evoked Cardiac Response 1 (ECR1), a brief modest deceleration evoked by simple sensory stimuli that is thought to reflect an early process of stimulus registration. Immediately following these pip-evoked decelerations, modest fast accelerations were observed. These accelerations were larger when the pip series was followed by shock than when it was not followed by shock. We propose a potential linkage between these accelerations and the human acceleratory ECR2 component, which is associated with more elaborate processing following stimulus registration; something likely to take place when the pip series predicts an aversive event. Both the ECR1- and ECR2-like responses were embedded within a slow, gradual heart rate increase across the entire pip series. This tonic increase was significantly larger on trials with footshock and is therefore probably associated with anticipatory fear of the upcoming shock. An additional special type of cardiac response was found to the first pip in the series not preceded by the safety signal; here, a much larger and more sustained deceleration was apparent. This response appears relatable to the prolonged deceleration reported in humans in response to aversive picture content. We discuss the cardiac responses found in rats in the current study in the context of heart rate responses known in the human literature.

  2. Juvenile stress potentiates aversive 22-kHz ultrasonic vocalizations and freezing during auditory fear conditioning in adult male rats.

    Science.gov (United States)

    Yee, Nicole; Schwarting, Rainer K W; Fuchs, Eberhard; Wöhr, Markus

    2012-09-01

    Traumatic experiences that occur during adolescence can render individuals vulnerable to mood and anxiety disorders. A model in juvenile rats (age: 27-29 days) was developed previously to study the long-term effects of adolescent stress exposure on behaviour and physiology. This paradigm, termed juvenile stress, involves subjecting juvenile rats to different stressors on consecutive days over a 3-day period. Here, we investigated the effects of the juvenile stress paradigm on freezing behaviour and aversive 22-kHz ultrasonic vocalizations (USVs) during auditory fear conditioning in adult male rats (age: 68-90 days). We found that rats previously subjected to juvenile stress increased aversive 22-kHz USVs (total calls and time spent calling) compared with controls during fear-conditioning training. The acoustic USV parameters between control and juvenile stress rats were largely equivalent, including duration, peak frequency and amplitude. While rats did not differ in freezing behaviour during fear conditioning, juvenile stress rats exhibited greater cue-conditioned freezing upon testing 24 h later. Our results show that juvenile stress elicited different long-term changes in freezing and aversive USVs during fear conditioning. Furthermore, they highlight the importance of assessing USVs to detect experience-dependent differences between control and stress-exposed animals which are not detectable by measuring visible behaviour.

  3. Modulation of gene expression in contextual fear conditioning in the rat.

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    Giuseppe Federighi

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

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

    Science.gov (United States)

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

    2013-01-01

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

  5. Benzodiazepine-induced anxiolysis and reduction of conditioned fear are mediated by distinct GABAA receptor subtypes in mice.

    Science.gov (United States)

    Smith, Kiersten S; Engin, Elif; Meloni, Edward G; Rudolph, Uwe

    2012-08-01

    GABA(A) receptor modulating drugs such as benzodiazepines (BZs) have been used to treat anxiety disorders for over five decades. In order to determine whether the same or different GABA(A) receptor subtypes are necessary for the anxiolytic-like action of BZs in unconditioned anxiety and conditioned fear models, we investigated the role of different GABA(A) receptor subtypes by challenging wild type, α1(H101R), α2(H101R) and α3(H126R) mice bred on the C57BL/6J background with diazepam or chlordiazepoxide in the elevated plus maze and the fear-potentiated startle paradigms. Both drugs significantly increased open arm exploration in the elevated plus maze in wild type, α1(H101R) and α3(H126R), but this effect was abolished in α2(H101R) mice; these were expected results based on previous published results. In contrast, while administration of diazepam and chlordiazepoxide significantly attenuated fear-potentiated startle (FPS) in wild type mice and α3(H126R) mice, the fear-reducing effects of these drugs were absent in both α1(H101R) and α2(H101R) point mutants, indicating that both α1- and α2-containing GABA(A) receptors are necessary for BZs to exert their effects on conditioned fear responses. Our findings illustrate both an overlap and a divergence between the GABA(A) receptor subtype requirements for the impact of BZs, specifically that both α1- and α2-containing GABA(A) receptors are necessary for BZs to reduce conditioned fear whereas only α2-containing GABA(A) receptors are needed for BZ-induced anxiolysis in unconditioned tests of anxiety. This raises the possibility that GABAergic pharmacological interventions for specific anxiety disorders can be differentially tailored.

  6. Hippocampal unit activity during classical aversive and appetitive conditioning.

    Science.gov (United States)

    Segal, M; Disterhoft, J F; Olds, J

    1972-02-18

    Rats were trained with a tone being followed by either food or electric shock, on alternate days. Unit activity during application of the conditioned stimulus was recorded from the dorsal hippocampus. The results indicate differentiation of the hippocampal system. Dentate units respond by augmentation to a conditioned stimulus which leads to food and by inhibition to the same stimulus when it precedes electric shock. The hippocampus proper responds by augmentation in both situations. The intensity of the hippocampal response to the conditioned stimulus on the first day of training is higher if the unconditioned stimulus is food than if it is electric shock. These data cast light on the functions of the dorsal dentate-hippocampal connections and the hippocampus proper during aversive and appetitive conditioning.

  7. Role of L-Type Ca[superscript 2+] Channel Isoforms in the Extinction of Conditioned Fear

    Science.gov (United States)

    Busquet, Perrine; Hetzenauer, Alfred; Sinnegger-Brauns, Martina J.; Striessnig, Jorg; Singewald, Nicolas

    2008-01-01

    Dihydropyridine (DHP) L-type Ca[superscript 2+] channel (LTCC) antagonists, such as nifedipine, have been reported to impair the extinction of conditioned fear without interfering with its acquisition. Identification of the LTCC isoforms mediating this DHP effect is an essential basis to reveal their role as potential drug targets for the…

  8. Fear conditioning and shock intensity : the choice between minimizing the stress induced and reducing the number of animals used

    NARCIS (Netherlands)

    Pietersen, CY; Bosker, FJ; Posterna, F; den Boer, JA

    2006-01-01

    Many fear conditioning studies use electric shock as the aversive stimulus. The intensity of shocks varies throughout the literature. In this study, shock intensities ranging from 0 to 1.5 mA were used, and the effects on the rats assessed by both behavioural and biochemical stress parameters. Resul

  9. Fear conditioning and shock intensity: the choice between minimizing the stress induced and reducing the number of animals used

    NARCIS (Netherlands)

    Pietersen, C.Y.; Bosker, F.J; Posterna, F.; Den Boer, J.A.

    2006-01-01

    Many fear conditioning studies use electric shock as the aversive stimulus. The intensity of shocks varies throughout the literature. In this study, shock intensities ranging from 0 to 1.5 mA were used, and the effects on the rats assessed by both behavioural and biochemical stress parameters. Resul

  10. Pavlovian fear conditioning regulates Thr286 autophosphorylation of Ca2+/calmodulin-dependent protein kinase II at lateral amygdala synapses.

    Science.gov (United States)

    Rodrigues, Sarina M; Farb, Claudia R; Bauer, Elizabeth P; LeDoux, Joseph E; Schafe, Glenn E

    2004-03-31

    Ca2+/calmodulin-dependent protein kinase II (CaMKII) plays a critical role in synaptic plasticity and memory formation in a variety of learning systems and species. The present experiments examined the role of CaMKII in the circuitry underlying pavlovian fear conditioning. First, we reveal by immunocytochemical and tract-tracing methods that alphaCaMKII is postsynaptic to auditory thalamic inputs and colocalized with the NR2B subunit of the NMDA receptor. Furthermore, we show that fear conditioning results in an increase of the autophosphorylated (active) form of alphaCaMKII in lateral amygdala (LA) spines. Next, we demonstrate that intra-amygdala infusion of a CaMK inhibitor, 1-[NO-bis-1,5-isoquinolinesulfonyl]-N-methyl-l-tyrosyl-4-phenylpiperazine, KN-62, dose-dependently impairs the acquisition, but not the expression, of auditory and contextual fear conditioning. Finally, in electrophysiological experiments, we demonstrate that an NMDA receptor-dependent form of long-term potentiation at thalamic input synapses to the LA is impaired by bath application of KN-62 in vitro. Together, the results of these experiments provide the first comprehensive view of the role of CaMKII in the amygdala during fear conditioning.

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

    Science.gov (United States)

    Laurent, Vincent; Westbrook, R. Frederick

    2008-01-01

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

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

    Science.gov (United States)

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

    2007-01-01

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

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

    Science.gov (United States)

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

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Jan Haaker

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

  15. Behavioral determination of stimulus pair discrimination of auditory acoustic and electrical stimuli using a classical conditioning and heart-rate approach.

    Science.gov (United States)

    Morgan, Simeon J; Paolini, Antonio G

    2012-06-06

    Acute animal preparations have been used in research prospectively investigating electrode designs and stimulation techniques for integration into neural auditory prostheses, such as auditory brainstem implants and auditory midbrain implants. While acute experiments can give initial insight to the effectiveness of the implant, testing the chronically implanted and awake animals provides the advantage of examining the psychophysical properties of the sensations induced using implanted devices. Several techniques such as reward-based operant conditioning, conditioned avoidance, or classical fear conditioning have been used to provide behavioral confirmation of detection of a relevant stimulus attribute. Selection of a technique involves balancing aspects including time efficiency (often poor in reward-based approaches), the ability to test a plurality of stimulus attributes simultaneously (limited in conditioned avoidance), and measure reliability of repeated stimuli (a potential constraint when physiological measures are employed). Here, a classical fear conditioning behavioral method is presented which may be used to simultaneously test both detection of a stimulus, and discrimination between two stimuli. Heart-rate is used as a measure of fear response, which reduces or eliminates the requirement for time-consuming video coding for freeze behaviour or other such measures (although such measures could be included to provide convergent evidence). Animals were conditioned using these techniques in three 2-hour conditioning sessions, each providing 48 stimulus trials. Subsequent 48-trial testing sessions were then used to test for detection of each stimulus in presented pairs, and test discrimination between the member stimuli of each pair. This behavioral method is presented in the context of its utilisation in auditory prosthetic research. The implantation of electrocardiogram telemetry devices is shown. Subsequent implantation of brain electrodes into the Cochlear

  16. Classical Conditioning of Hippocampal Theta Patterns in the Rat.

    Science.gov (United States)

    1976-08-01

    associated with changes in performance of learned tasks , 1,4,5, 8,9 there have been very few studies of neurona l plasticity of the hippocampus It self...rapid development of a conditioned hippocampal theta response to a visual sti mulus demonstrates tha t there is considerable neurona l plasticity in the

  17. Extinction and retrieval+extinction of conditioned fear differentially activate medial prefrontal cortex and amygdala in rats

    Directory of Open Access Journals (Sweden)

    Hongjoo Joanne Lee

    2016-01-01

    Full Text Available 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 2 approaches using Arc catFISH (cellular compartment analysis of temporal activity using fluorescence in situ hybridization. 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 rats.

  18. Conditional Similarity Reductions of Jimbo-Miwa Equation via the Classical Lie Group Approach

    Institute of Scientific and Technical Information of China (English)

    TANG Xiao-Yan; LIN Ji

    2003-01-01

    Recently, the Clarkson and Kruskal direct method has been modified to find new similarity reductions (conditional similarity reductions) of nonlinear systems and the results obtained by the modified direct method cannot be obtained by the current classical and/or non-classical Lie group approach. In this paper, we show that the conditional similarity reductions of the Jimbo-Miwa equation can be reobtained by adding an additional constraint equation to the original model to form a conditional equation system first and then solving the model system by means of the classical Lie group approach.

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

    Science.gov (United States)

    McKinney, Brandon C.; Murphy, Geoffrey G.

    2006-01-01

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

  20. The Operant and the Classical in Conditioned Orientation of Drosophila melanogaster at the Flight Simulator

    Science.gov (United States)

    Brembs, Björn; Heisenberg, Martin

    2000-01-01

    Ever since learning and memory have been studied experimentally, the relationship between operant and classical conditioning has been controversial. Operant conditioning is any form of conditioning that essentially depends on the animal's behavior. It relies on operant behavior. A motor output is called operant if it controls a sensory variable. The Drosophila flight simulator, in which the relevant behavior is a single motor variable (yaw torque), fully separates the operant and classical components of a complex conditioning task. In this paradigm a tethered fly learns, operantly or classically, to prefer and avoid certain flight orientations in relation to the surrounding panorama. Yaw torque is recorded and, in the operant mode, controls the panorama. Using a yoked control, we show that classical pattern learning necessitates more extensive training than operant pattern learning. We compare in detail the microstructure of yaw torque after classical and operant training but find no evidence for acquired behavioral traits after operant conditioning that might explain this difference. We therefore conclude that the operant behavior has a facilitating effect on the classical training. In addition, we show that an operantly learned stimulus is successfully transferred from the behavior of the training to a different behavior. This result unequivocally demonstrates that during operant conditioning classical associations can be formed. PMID:10753977

  1. Age differences in fear retention and extinction in male Sprague-Dawley rats: effects of ethanol challenge during conditioning.

    Science.gov (United States)

    Broadwater, Margaret; Spear, Linda P

    2013-09-01

    Pavlovian fear conditioning is an ideal model to investigate how learning and memory are influenced by alcohol use during adolescence because the neural mechanisms involved have been studied extensively. In Exp 1, adolescent and adult male Sprague-Dawley rats were non-injected or injected with saline, 1 or 1.5 g/kg ethanol intraperitoneally 10 min prior to tone or context conditioning. Twenty-four hours later, animals were tested for tone or context retention and extinction, with examination of extinction retention conducted 24h thereafter. In Exp 2, a context extinction session was inserted between the tone conditioning and the tone fear retention/extinction days to reduce pre-CS baseline freezing levels at test. Basal levels of acquisition, fear retention, extinction, and extinction retention after tone conditioning were similar between adolescent and adult rats. In contrast adolescents showed faster context extinction than adults, while again not differing from adults during context acquisition, retention or extinction retention. In terms of ethanol effects, adolescents were less sensitive to ethanol-induced context retention deficits than adults. No age differences emerged in terms of tone fear retention, with ethanol disrupting tone fear retention at both ages in Exp 1, but at neither age in Exp 2, a difference seemingly due to group differences in pre-CS freezing during tone testing in Exp 1, but not Exp 2. These results suggest that age differences in the acute effects of ethanol on cognitive function are task-specific, and provide further evidence for age differences cognitive functioning in a task thought to be hippocampally related.

  2. Testicular hormones do not regulate sexually dimorphic Pavlovian fear conditioning or perforant-path long-term potentiation in adult male rats.

    Science.gov (United States)

    Anagnostaras, S G; Maren, S; DeCola, J P; Lane, N I; Gale, G D; Schlinger, B A; Fanselow, M S

    1998-04-01

    We recently reported that Pavlovian fear conditioning and hippocampal perforant-path long-term potentiation (LTP) are sexually dimorphic in rats. Males show greater contextual fear conditioning, which depends on the hippocampus, as well as greater hippocampal LTP. In order to examine the role of circulating gonadal hormones in adult male rats, animals were castrated in two experiments, and Pavlovian fear conditioning and in vivo perforant-path LTP were examined. It was found that sexually-dimorphic LTP and fear conditioning are not regulated by the activational effects of testicular hormones in adult male rats. That is, in every respect, castrated male rats were similar to intact male rats in Pavlovian fear conditioning and hippocampal LTP. It is likely that sexual dimorphism in this system is established earlier in development by the organizational effects of gonadal hormones.

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

    Directory of Open Access Journals (Sweden)

    Valérie Manceau

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

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

    Directory of Open Access Journals (Sweden)

    Matthew Valley

    2009-11-01

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

  5. PACAP modulates the consolidation and extinction of the contextual fear conditioning through NMDA receptors.

    Science.gov (United States)

    Schmidt, S D; Myskiw, J C; Furini, C R G; Schmidt, B E; Cavalcante, L E; Izquierdo, I

    2015-02-01

    Pituitary adenylate cyclase-activating polypeptide (PACAP) has a broad spectrum of biological functions including neurotransmitter, neurotrophic and neuroprotective. Moreover, it has been suggested that PACAP plays a role in the modulation of learning and memory as well as on the modulation of glutamate signaling. Thus, in the current study we investigated in the CA1 region of hippocampus and in the basolateral amygdala (BLA) the role of PACAP in the consolidation and extinction of contextual fear conditioning (CFC) and the interaction between PACAP and NMDA receptors. Male rats with cannulae implanted in the CA1 region of the hippocampus or in the BLA received immediately after the training or extinction training of the CFC infusions of the Vehicle, PACAP-38 (40 pg/side), PACAP 6-38 (40 pg/side) or PACAP 6-38 plus D-serine (50 μg/side). After 24h, the animals were subjected to a 3-min retention test. The results indicated that in the CA1 region of hippocampus, PACAP participates in the consolidation and extinction of the CFC, and in the BLA, PACAP participates only in the consolidation of the CFC. Additionally, the results suggest that the action of PACAP on the consolidation and extinction of the CFC is mediated by the glutamate NMDA receptors.

  6. Acquisition of contextual Pavlovian fear conditioning is blocked by application of an NMDA receptor antagonist D,L-2-amino-5-phosphonovaleric acid to the basolateral amygdala.

    Science.gov (United States)

    Fanselow, M S; Kim, J J

    1994-02-01

    Rats, with chronic cannula placed bilaterally in the amygdala, received infusions of the N-methyl-D-aspartate (NMDA) receptor antagonist D,L-2-amino-5-phosphonovaleric acid (APV) before contextual Pavlovian fear conditioning. Administration of APV to the basolateral nucleus prevented acquisition of fear. Central nucleus infusions had no effect. It is concluded that an NMDA-mediated process near the basolateral region of the amygdala (e.g., lateral or basolateral nucleus) is essential for the learning of fear.

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

    Directory of Open Access Journals (Sweden)

    Maria Toledo-Rodriguez

    2007-01-01

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

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

    Science.gov (United States)

    Careaga, Mariella B. L.; Tiba, Paula A.; Ota, Simone M.; Suchecki, Deborah

    2015-01-01

    Cognitive processes, such as learning and memory, are essential for our adaptation to environmental changes and consequently for survival. Numerous studies indicate that hormones secreted during stressful situations, such as glucocorticoids (GCs), adrenaline and noradrenaline, regulate memory functions, modulating aversive memory consolidation and retrieval, in an interactive and complementary way. Thus, the facilitatory effects of GCs on memory consolidation as well as their suppressive effects on retrieval are substantially explained by this interaction. On the other hand, low levels of GCs are also associated with negative effects on memory consolidation and retrieval and the mechanisms involved are not well understood. The present study sought to investigate the consequences of blocking the rise of GCs on fear memory retrieval in multiple tests, assessing the participation of β-adrenergic signaling on this effect. Metyrapone (GCs synthesis inhibitor; 75 mg/kg), administered 90 min before the first test of contextual or tone fear conditioning (TFC), negatively affected animals’ performances, but this effect did not persist on a subsequent test, when the conditioned response was again expressed. This result suggested that the treatment impaired fear memory retrieval during the first evaluation. The administration immediately after the first test did not affect the animals’ performances in contextual fear conditioning (CFC), suggesting that the drug did not interfere with processes triggered by memory reactivation. Moreover, metyrapone effects were independent of β-adrenergic signaling, since concurrent administration with propranolol (2 mg/kg), a β-adrenergic antagonist, did not modify the effects induced by metyrapone alone. These results demonstrate that pre-test metyrapone administration led to negative effects on fear memory retrieval and this action was independent of a β-adrenergic signaling. PMID:25784866

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

    Directory of Open Access Journals (Sweden)

    Mariella B.L. Careaga

    2015-03-01

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

  10. Differential modulation of changes in hippocampal-septal synaptic excitability by the amygdala as a function of either elemental or contextual fear conditioning in mice.

    Science.gov (United States)

    Desmedt, A; Garcia, R; Jaffard, R

    1998-01-01

    Recent data obtained using a classic fear conditioning paradigm showed a dissociation between the retention of associations relative to contextual information (dependent on the hippocampal formation) and the retention of elemental associations (dependent on the amygdala). Furthermore, it was reported that conditioned emotional responses (CERs) could be dissociated from the recollection of the learning experience (declarative memory) in humans and from modifications of the hippocampal-septal excitability in animals. Our aim was to determine whether these two systems ("behavioral expression" system and "factual memory" system) interact by examining the consequences of amygdalar lesions (1) on the modifications of hippocampal-septal excitability and (2) on the behavioral expression of fear (freezing) resulting from an aversive conditioning during reexposure to conditional stimuli (CSs). During conditioning, to modulate the predictive nature of the context and of a discrete stimulus (tone) on the unconditional stimulus (US) occurrence, the phasic discrete CS was paired with the US or randomly distributed with regard to the US. After the lesion, the CER was dramatically reduced during reexposure to the CSs, whatever the type of acquisition. However, the changes in hippocampal-septal excitability persisted but were altered. For controls, a decrease in septal excitability was observed during reexposure to the conditioning context only for the "unpaired group" (predictive context case). Conversely, among lesioned subjects this decrease was observed in the "paired group" (predictive discrete CS case), whereas this decrease was significantly reduced in the unpaired group with respect to the matched control group. The amplitude and the direction of these modifications suggest a differential modulation of hippocampal-septal excitability by the amygdala to amplify the contribution of the more predictive association signaling the occurrence of the aversive event.

  11. The role of dopamine in Drosophila larval classical olfactory conditioning.

    Directory of Open Access Journals (Sweden)

    Mareike Selcho

    Full Text Available Learning and memory is not an attribute of higher animals. Even Drosophila larvae are able to form and recall an association of a given odor with an aversive or appetitive gustatory reinforcer. As the Drosophila larva has turned into a particularly simple model for studying odor processing, a detailed neuronal and functional map of the olfactory pathway is available up to the third order neurons in the mushroom bodies. At this point, a convergence of olfactory processing and gustatory reinforcement is suggested to underlie associative memory formation. The dopaminergic system was shown to be involved in mammalian and insect olfactory conditioning. To analyze the anatomy and function of the larval dopaminergic system, we first characterize dopaminergic neurons immunohistochemically up to the single cell level and subsequent test for the effects of distortions in the dopamine system upon aversive (odor-salt as well as appetitive (odor-sugar associative learning. Single cell analysis suggests that dopaminergic neurons do not directly connect gustatory input in the larval suboesophageal ganglion to olfactory information in the mushroom bodies. However, a number of dopaminergic neurons innervate different regions of the brain, including protocerebra, mushroom bodies and suboesophageal ganglion. We found that dopamine receptors are highly enriched in the mushroom bodies and that aversive and appetitive olfactory learning is strongly impaired in dopamine receptor mutants. Genetically interfering with dopaminergic signaling supports this finding, although our data do not exclude on naïve odor and sugar preferences of the larvae. Our data suggest that dopaminergic neurons provide input to different brain regions including protocerebra, suboesophageal ganglion and mushroom bodies by more than one route. We therefore propose that different types of dopaminergic neurons might be involved in different types of signaling necessary for aversive and appetitive

  12. Classical Conditioning of Eyelid and Mystacial Vibrissae Responses in Conscious Mice

    Science.gov (United States)

    Delgado-Garcia, Jose Maria; Troncoso, Julieta; Munera, Alejandro

    2004-01-01

    The murine vibrissae sensorimotor system has been scrutinized as a target of motor learning through trace classical conditioning. Conditioned eyelid responses were acquired by using weak electrical whisker-pad stimulation as conditioned stimulus (CS) and strong electrical periorbital stimulation as unconditioned stimulus (US). In addition,…

  13. Oxytocin Signaling in Basolateral and Central Amygdala Nuclei Differentially Regulates the Acquisition, Expression, and Extinction of Context-Conditioned Fear in Rats

    Science.gov (United States)

    Campbell-Smith, Emma J.; Holmes, Nathan M.; Lingawi, Nura W.; Panayi, Marios C.; Westbrook, R. Frederick

    2015-01-01

    The present study investigated how oxytocin (OT) signaling in the central (CeA) and basolateral (BLA) amygdala affects acquisition, expression, and extinction of context-conditioned fear (freezing) in rats. In the first set of experiments, acquisition of fear to a shocked context was impaired by a preconditioning infusion of synthetic OT into the…

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

    Science.gov (United States)

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

    2004-01-01

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

  15. Cat odor causes long-lasting contextual fear conditioning and increased pituitary-adrenal activation, without modifying anxiety.

    Science.gov (United States)

    Muñoz-Abellán, Cristina; Daviu, Nuria; Rabasa, Cristina; Nadal, Roser; Armario, Antonio

    2009-10-01

    A single exposure to a cat or cat odors has been reported by some groups to induce contextual and auditory fear conditioning and long-lasting changes in anxiety-like behaviour, but there is no evidence for parallel changes in biological stress markers. In the present study we demonstrated in male rats that exposure to a novel environment containing a cloth impregnated with cat fur odor resulted in avoidance of the odor, lower levels of activity and higher pituitary-adrenal (PA) response as compared to those exposed to the novel environment containing a clean cloth, suggesting increased levels of stress in the former animals. When re-exposed 9 days later to the same environment with a clean cloth, previously cat fur exposed rats again showed avoidance of the cloth area and lower levels of activity, suggesting development of contextual fear conditioning, which again was associated with a higher PA activation. In contrast, unaltered both anxiety-like behaviour and PA responsiveness to an elevated plus-maze were found 7 days after cat odor exposure. It is concluded that: (i) PA activation is able to reflect both the stressful properties of cat fur odor and odor-induced contextual fear conditioning; (ii) development of cat odor-induced contextual fear conditioning is independent of the induction of long-lasting changes in anxiety-like behaviour; and (iii) greater PA activation during exposure to the odor context is not explained by non-specific sensitization of the PA axis caused by previous exposure to cat fur odor.

  16. Rethinking the fear circuit: the central nucleus of the amygdala is required for the acquisition, consolidation, and expression of Pavlovian fear conditioning

    DEFF Research Database (Denmark)

    Wilensky, Ann E; Schafe, Glenn E; Kristensen, Morten Pilgaard;

    2006-01-01

    In the standard model of pavlovian fear learning, sensory input from neutral and aversive stimuli converge in the lateral nucleus of the amygdala (LA), in which alterations in synaptic transmission encode the association. During fear expression, the LA is thought to engage the central nucleus...

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

    Directory of Open Access Journals (Sweden)

    Xinwen eDong

    2015-06-01

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

  18. A review on experimental and clinical genetic associations studies on fear conditioning, extinction and cognitive-behavioral treatment.

    Science.gov (United States)

    Lonsdorf, T B; Kalisch, R

    2011-09-20

    Fear conditioning and extinction represent basic forms of associative learning with considerable clinical relevance and have been implicated in the pathogenesis of anxiety disorders. There is considerable inter-individual variation in the ability to acquire and extinguish conditioned fear reactions and the study of genetic variants has recently become a focus of research. In this review, we give an overview of the existing genetic association studies on human fear conditioning and extinction in healthy individuals and of related studies on cognitive-behavioral treatment (CBT) and exposure, as well as pathology development after trauma. Variation in the serotonin transporter (5HTT) and the catechol-o-methyltransferase (COMT) genes has consistently been associated with effects in pre-clinical and clinical studies. Interesting new findings, which however require further replication, have been reported for genetic variation in the dopamine transporter (DAT1) and the pituitary adenylate cyclase 1 receptor (ADCYAP1R1) genes, whereas the current picture is inconsistent for variation in the brain-derived neurotrophic factor (BDNF) gene. We end with a discussion of the findings and their limitations, as well as future directions that we hope will aid the field to develop further.

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

    NARCIS (Netherlands)

    Kindt, M.; Soeter, M.

    2013-01-01

    Disrupting reconsolidation seems to be a promising approach to dampen the expression of fear memory. Recently, we demonstrated that disrupting reconsolidation by a pharmacological manipulation specifically targeted the emotional expression of memory (i.e., startle response). Here we test in a human

  20. Sleep deprivation impairs contextual fear conditioning and attenuates subsequent behavioural, endocrine and neuronal responses

    NARCIS (Netherlands)

    Hagewoud, Roelina; Bultsma, Lillian J.; Barf, R. Paulien; Koolhaas, Jaap M.; Meerlo, Peter

    2011-01-01

    Sleep deprivation (SD) affects hippocampus-dependent memory formation. Several studies in rodents have shown that brief SD immediately following a mild foot shock impairs consolidation of contextual fear memory as reflected in a reduced behavioural freezing response during re-exposure to the shock c

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Science.gov (United States)

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

    2004-01-01

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

  3. Studies in Early Infant Learning: Classical Conditioning of the Neonatal Heart Rate

    Science.gov (United States)

    Crowell, David H.; And Others

    1976-01-01

    In three experiments, it was demonstrated that human newborn heart rate level can be reliably modified through classical conditioning procedures. Findings support the idea that early learning may occur under a variety of conditions and different theories may account for the results. (Author/SB)

  4. Classical Conditioning and Retention of the Infant's Eyelid Response: Effects of Age and Interstimulus Interval.

    Science.gov (United States)

    Little, Arlene H.; And Others

    1984-01-01

    Reports that lengthy interstimulus interval facilitates classical conditioning in very young infants. Infants trained in a single session at 20 days of age exhibited reliable retention of the conditioned eyelid reflex 10 days later, but infants 10 days of age did not. (Author)

  5. Feeding Behavior of Aplysia: A Model System for Comparing Cellular Mechanisms of Classical and Operant Conditioning

    Science.gov (United States)

    Baxter, Douglas A.; Byrne, John H.

    2006-01-01

    Feeding behavior of Aplysia provides an excellent model system for analyzing and comparing mechanisms underlying appetitive classical conditioning and reward operant conditioning. Behavioral protocols have been developed for both forms of associative learning, both of which increase the occurrence of biting following training. Because the neural…

  6. Agoraphobia: Fear of Fear.

    Science.gov (United States)

    Musetto, Andrew P.

    1984-01-01

    Agoraphobia is a complex phobia in which individuals react with intense anxiety to certain stress situations. Basically, agoraphobics live in fear of becoming afraid. Describes the psychotherapeutic treatment that helps agoraphobics to become more self-sufficient and to face their fears by understanding themselves better. (CS)

  7. Viral delivery of shRNA to amygdala neurons leads to neurotoxicity and deficits in Pavlovian fear conditioning.

    Science.gov (United States)

    de Solis, Christopher A; Holehonnur, Roopashri; Banerjee, Anwesha; Luong, Jonathan A; Lella, Srihari K; Ho, Anthony; Pahlavan, Bahram; Ploski, Jonathan E

    2015-10-01

    The use of viral vector technology to deliver short hairpin RNAs (shRNAs) to cells of the nervous system of many model organisms has been widely utilized by neuroscientists to study the influence of genes on behavior. However, there have been numerous reports that delivering shRNAs to the nervous system can lead to neurotoxicity. Here we report the results of a series of experiments where adeno-associated viruses (AAV), that were engineered to express shRNAs designed to target known plasticity associated genes (i.e. Arc, Egr1 and GluN2A) or control shRNAs that were designed not to target any rat gene product for depletion, were delivered to the rat basal and lateral nuclei of the amygdala (BLA), and auditory Pavlovian fear conditioning was examined. In our first set of experiments we found that animals that received AAV (3.16E13-1E13 GC/mL; 1 μl/side), designed to knockdown Arc (shArc), or control shRNAs targeting either luciferase (shLuc), or nothing (shCntrl), exhibited impaired fear conditioning compared to animals that received viruses that did not express shRNAs. Notably, animals that received shArc did not exhibit differences in fear conditioning compared to animals that received control shRNAs despite gene knockdown of Arc. Viruses designed to harbor shRNAs did not induce obvious morphological changes to the cells/tissue of the BLA at any dose of virus tested, but at the highest dose of shRNA virus examined (3.16E13 GC/mL; 1 μl/side), a significant increase in microglia activation occurred as measured by an increase in IBA1 immunoreactivity. In our final set of experiments we infused viruses into the BLA at a titer of (1.60E+12 GC/mL; 1 μl/side), designed to express shArc, shLuc, shCntrl or shRNAs designed to target Egr1 (shEgr1), or GluN2A (shGluN2A), or no shRNA, and found that all groups exhibited impaired fear conditioning compared to the group which received a virus that did not express an shRNA. The shEgr1 and shGluN2A groups exhibited gene

  8. Vagus nerve stimulation enhances extinction of conditioned fear and modulates plasticity in the pathway from the infralimbic prefrontal cortex to the amygdala.

    Directory of Open Access Journals (Sweden)

    David Frausto Peña

    2014-09-01

    Full Text Available Fearful experiences can produce long-lasting and debilitating memories. Extinction of the fear response requires consolidation of new memories that compete with fearful associations. Subjects with posttraumatic stress disorder (PTSD show impaired extinction of conditioned fear, which is associated with decreased ventromedial prefrontal cortex (vmPFC control over amygdala activity. Vagus nerve stimulation (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 investigated whether pairing VNS with extinction learning facilitates plasticity between the infralimbic (IL medial prefrontal cortex and the basolateral complex of the amygdala (BLA. Rats were trained on an auditory fear conditioning task, which was followed by a retention test and one day of extinction training. Vagus nerve stimulation or sham-stimulation was administered concurrently with exposure to the fear-conditioned stimulus and retention of fear conditioning was tested again 24 hours later. VNS-treated rats demonstrated a significant reduction in freezing after a single extinction training session similar to animals that received 5x the number of extinction pairings. To study plasticity in the IL-BLA pathway, we recorded evoked field potentials in the BLA in anesthetized animals 24 h after retention testing. Brief burst stimulation in the IL produced LTD in the BLA field response in fear-conditioned and sham-treated animals. In contrast, the same stimulation resulted in potentiation of the IL-BLA pathway in the VNS-treated group. The present findings suggest that VNS promotes plasticity in the IL-BLA pathway to facilitate extinction of conditioned fear responses.

  9. Quantum versus classical foundation of statistical mechanics under experimentally realistic conditions.

    Science.gov (United States)

    Reimann, Peter; Evstigneev, Mykhaylo

    2013-11-01

    Focusing on isolated macroscopic systems, described in terms of either a quantum mechanical or a classical model, our two key questions are how far does an initial ensemble (usually far from equilibrium and largely unknown in detail) evolve towards a stationary long-time behavior (equilibration) and how far is this steady state in agreement with the microcanonical ensemble as predicted by statistical mechanics (thermalization). A recently developed quantum mechanical treatment of the problem is briefly summarized, putting particular emphasis on the realistic modeling of experimental measurements and nonequilibrium initial conditions. Within this framework, equilibration can be proven under very weak assumptions about those measurements and initial conditions, while thermalization still requires quite strong additional hypotheses. An analogous approach within the framework of classical mechanics is developed and compared with the quantum case. In particular, the assumptions to guarantee classical equilibration are now rather strong, while thermalization then follows under relatively weak additional conditions.

  10. Special issue on computational models of classical conditioning guest editors' introduction.

    Science.gov (United States)

    Alonso, Eduardo; Schmajuk, Nestor

    2012-09-01

    In the present special issue, the performance of current computational models of classical conditioning was evaluated under three requirements: (1) Models were to be tested against a list of previously agreed-upon phenomena; (2) the parameters were fixed across simulations; and (3) the simulations used to test the models had to be made available. These requirements resulted in three major products: (a) a list of fundamental classical-conditioning results for which there is a consensus about their reliability; (b) the necessary information to evaluate each of the models on the basis of its ordinal successes in accounting for the experimental data; and (c) a repository of computational models ready to generate simulations. We believe that the contents of this issue represent the 2012 state of the art in computational modeling of classical conditioning and provide a way to find promising avenues for future model development.

  11. Sea slugs, subliminal pictures and vegetative state patients: Boundaries of consciousness in classical conditioning.

    Directory of Open Access Journals (Sweden)

    Tristan A Bekinschtein

    2011-12-01

    Full Text Available Classical (trace conditioning is a specific variant of associative learning in which a neutral stimulus leads to the subsequent prediction of an emotionally charged or noxious stimulus after a temporal gap. When conditioning is concurrent with a distraction task, only participants who can report the relationship (the contingency between stimuli explicitly show associative learning. This suggests that consciousness is a prerequisite for trace conditioning. We review and question three main controversies concerning this view. Firstly, virtually all animals, even invertebrate sea slugs, show this type of learning; secondly, unconsciously perceived stimuli may elicit trace conditioning; and thirdly, some vegetative state patients show trace learning. We discuss and analyze these seemingly contradictory arguments to find the theoretical boundaries of consciousness in classical conditioning. We conclude that trace conditioning remains one of the best measures to test conscious processing in the absence of explicit reports.

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

    Science.gov (United States)

    Ledgerwood, Lana; Richardson, Rick; Cranney, Jacquelyn

    2004-06-01

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

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

    Science.gov (United States)

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

    2006-08-15

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

  14. Role of Sleep Deprivation in Fear Conditioning and Extinction: Implications for Treatment of PTSD

    Science.gov (United States)

    2015-12-01

    and distressing symptoms of PTSD are insomnia and nightmares. The resultant sleep deprivation may actually serve to perpetuate the disorder by... accounted for by safety signal learning. Overnight REM sleep was, in turn, related to overnight retention of fear and safety learning, with 6 22.5% of the...variance in startle retention accounted for by REM sleep. These data suggest sleep difficulties, specifically REM sleep fragmentation, may play a

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

    Directory of Open Access Journals (Sweden)

    Ewa Siucinska

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

  16. Lifelong disturbance of serotonin transporter functioning results in fear learning deficits: Reversal by blockade of CRF1 receptors.

    Science.gov (United States)

    Bijlsma, Elisabeth Y; Hendriksen, Hendrikus; Baas, Johanna M P; Millan, Mark J; Groenink, Lucianne

    2015-10-01

    The inability to associate aversive events with relevant cues (i.e. fear learning) may lead to maladaptive anxiety. To further study the role of the serotonin transporter (SERT) in fear learning, classical fear conditioning was studied in SERT knockout rats (SERT(-/-)) using fear potentiation of the startle reflex. Next, fear acquisition and concomitant development of contextual conditioned fear were monitored during training. To differentiate between developmental and direct effects of reduced SERT functioning, effects of acute and chronic SSRI treatment were studied in adult rats. Considering the known interactions between serotonin and corticotropin-releasing factor (CRF), we studied the effect of the CRFR1 antagonist CP154,526 on behavioral changes observed and determined CRF1 receptor levels in SERT(-/-) rats. SERT(-/-) showed blunted fear potentiation and enhanced contextual fear, which resulted from a deficit in fear acquisition. Paroxetine treatment did not affect acquisition or expression of fear-potentiated startle, suggesting that disturbed fear learning in SERT(-/-) results from developmental changes and not from reduced SERT functioning. Although CRF1 receptor levels did not differ significantly between genotypes, CP154,526 treatment normalized both cue- and contextual fear in SERT(-/-) during acquisition, but not expression of fear-potentiated startle. The disrupted fear acquisition and concomitant increase in contextual conditioned fear-potentiated startle fear in SERT(-/-) resembles the associative learning deficit seen in patients with panic disorder and suggests that normal SERT functioning is crucial for the development of an adequate fear neuro-circuitry. Moreover, the normalization of fear acquisition by CP154,526 suggests a role for central CRF signaling in the generalization of fear.

  17. Latent inhibition of cued fear conditioning: an NMDA receptor-dependent process that can be established in the presence of anisomycin.

    Science.gov (United States)

    Lewis, Michael C; Gould, Thomas J

    2004-08-01

    Much of the research examining the biological basis for long-term memories has focused on mechanisms that support the formation of conditioned associations. Less information is available on biological mechanisms which underlie processes that modify the strength of conditioned associations. Latent inhibition is a phenomenon by which pre-exposure to a to-be-conditioned stimulus (CS) weakens subsequent conditioning of that CS to an unconditioned stimulus (US). Here we report that latent inhibition of cued fear conditioning is dependent on NMDA receptor activation. MK-801 (1 mg/kg), an NMDA receptor antagonist, abolished latent inhibition of cued fear conditioning. This dose of MK-801 administered before training did not disrupt cued fear conditioning. Conversely, anisomycin (150 mg/kg), a protein synthesis inhibitor, had no effect on latent inhibition of cued fear conditioning when administered 20 min before, immediately after, or 2, 4, 6, or 8 h after CS pre-exposure. Furthermore, continuous anisomycin administration (50 mg/kg, administered every 2 h for 6 h starting 20 min prior to pre-exposure) did not disrupt latent inhibition of cued fear conditioning. In addition, anisomycin had no effect on a long-lasting version of latent inhibition of cued fear conditioning that was maintained over a 7-day interval. Anisomycin administered before training, however, disrupted learning of the CS-US association. These findings suggest that latent inhibition of cued fear conditioning is a long-lasting NMDA receptor-dependent process that can develop during the inhibition of protein synthesis.

  18. Investigating the non-classical boundary conditions relevant to strain gradient theories

    Science.gov (United States)

    Jafari, Akbar; Ezzati, Meysam

    2017-02-01

    In the present study, two classes of non-classical constitutive equations consisting of the first and the second order strain gradients theories (FSG and SSG) were applied in order to develop the governing equations of static and free vibrational behavior of beam structures. The governing equations in orders of six and eight were constructed for FSG and SSG theories, respectively. Therefore, higher order or in other words non-classical boundary conditions (HOBCs or NCBCs) came into play in addition to the classical ones (CBCs). Some explanations were presented about the concept of the non-classical boundary conditions. Analytical and finite element (FE) approaches were employed to solve the governing equations. The analytical solutions were utilized in validation and convergence study of FE results. Comparisons were made with the relevant data reported in the open literature; however, to the best of the authors' knowledge, few references have been published on SSG theory and HOBCs. In the numerical studies, the effects of applying different combinations of CBCs and HOBCs to the static and free vibration behaviors of the beam were investigated. Moreover, the impacts of non-classical elastic constants and the beam size on its behavior were also studied.

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

    Science.gov (United States)

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

    2007-01-01

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

  20. Classical Conditioning of Emotional Responses (Meaning, Attitudes, Values, Interests) and Effects on Social Behavior: A Bibliography.

    Science.gov (United States)

    Staats, Arthur W.; Carlson, Carl G.

    This is a bibliography of 81 papers and books published in the years 1957-1970 relevant to the subject of verbally-elicited responses that are in accordance with principles of classical conditioning. Of these publications, 24 are by Staats--one of the bibliographers--and his associates. (MF)

  1. Spike-coding mechanisms of cerebellar temporal processing in classical conditioning and voluntary movements.

    Science.gov (United States)

    Yamaguchi, Kenji; Sakurai, Yoshio

    2014-10-01

    Time is a fundamental and critical factor in daily life. Millisecond timing, which is the underlying temporal processing for speaking, dancing, and other activities, is reported to rely on the cerebellum. In this review, we discuss the cerebellar spike-coding mechanisms for temporal processing. Although the contribution of the cerebellum to both classical conditioning and voluntary movements is well known, the difference of the mechanisms for temporal processing between classical conditioning and voluntary movements is not clear. Therefore, we review the evidence of cerebellar temporal processing in studies of classical conditioning and voluntary movements and report the similarities and differences between them. From some studies, which used tasks that can change some of the temporal properties (e.g., the duration of interstimulus intervals) with keeping identical movements, we concluded that classical conditioning and voluntary movements may share a common spike-coding mechanism because simple spikes in Purkinje cells decrease at predicted times for responses regardless of the intervals between responses or stimulation.

  2. Cholinergic Septo-Hippocampal Innervation Is Required for Trace Eyeblink Classical Conditioning

    Science.gov (United States)

    Fontan-Lozano, Angela; Troncoso, Julieta; Munera, Alejandro; Carrion, Angel Manuel; Delgado-Garcia, Jose Maria

    2005-01-01

    We studied the effects of a selective lesion in rats, with 192-IgG-saporin, of the cholinergic neurons located in the medial septum/diagonal band (MSDB) complex on the acquisition of classical and instrumental conditioning paradigms. The MSDB lesion induced a marked deficit in the acquisition, but not in the retrieval, of eyeblink classical…

  3. Repeated Acquisitions and Extinctions in Classical Conditioning of the Rabbit Nictitating Membrane Response

    Science.gov (United States)

    Kehoe, E. James

    2006-01-01

    The rabbit nictitating membrane (NM) response underwent successive stages of acquisition and extinction training in both delay (Experiment 1) and trace (Experiment 2) classical conditioning. In both cases, successive acquisitions became progressively faster, although the largest, most reliable acceleration occurred between the first and second…

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

    NARCIS (Netherlands)

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

    2015-01-01

    Earlier studies provided preliminary support for the role of classical conditioning as a pathway of disgust learning, yet this evidence has been limited to self-report. This study included facial electromyographical (EMG) measurements (corrugator and levator muscles) and a behavioural approach task

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2015-11-01

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

  7. Glutamic acid decarboxylase 65: a link between GABAergic synaptic plasticity in the lateral amygdala and conditioned fear generalization.

    Science.gov (United States)

    Lange, Maren D; Jüngling, Kay; Paulukat, Linda; Vieler, Marc; Gaburro, Stefano; Sosulina, Ludmila; Blaesse, Peter; Sreepathi, Hari K; Ferraguti, Francesco; Pape, Hans-Christian

    2014-08-01

    An imbalance of the gamma-aminobutyric acid (GABA) system is considered a major neurobiological pathomechanism of anxiety, and the amygdala is a key brain region involved. Reduced GABA levels have been found in anxiety patients, and genetic variations of glutamic acid decarboxylase (GAD), the rate-limiting enzyme of GABA synthesis, have been associated with anxiety phenotypes in both humans and mice. These findings prompted us to hypothesize that a deficiency of GAD65, the GAD isoform controlling the availability of GABA as a transmitter, affects synaptic transmission and plasticity in the lateral amygdala (LA), and thereby interferes with fear responsiveness. Results indicate that genetically determined GAD65 deficiency in mice is associated with (1) increased synaptic length and release at GABAergic connections, (2) impaired efficacy of GABAergic synaptic transmission and plasticity, and (3) reduced spillover of GABA to presynaptic GABAB receptors, resulting in a loss of the associative nature of long-term synaptic plasticity at cortical inputs to LA principal neurons. (4) In addition, training with high shock intensities in wild-type mice mimicked the phenotype of GAD65 deficiency at both the behavioral and synaptic level, indicated by generalization of conditioned fear and a loss of the associative nature of synaptic plasticity in the LA. In conclusion, GAD65 is required for efficient GABAergic synaptic transmission and plasticity, and for maintaining extracellular GABA at a level needed for associative plasticity at cortical inputs in the LA, which, if disturbed, results in an impairment of the cue specificity of conditioned fear responses typifying anxiety disorders.

  8. A behavioral stages model of classical (Pavlovian) conditioning: application to cognitive aging.

    Science.gov (United States)

    Powell, D A

    1999-01-01

    In the present article, it is argued that a five-stage sequential model of the behavioral and neurophysiological events that occur when organisms are exposed to signals predicting significant events suggests that classical conditioning produces multiple memory traces involving both excitatory and inhibitory processes. Further, these multiple brain structures and associated neurophysiological mechanisms are beginning to be understood; thus, using Pavlovian conditioning techniques to study aging and cognitive functions may provide insights into which brain structures or mechanisms are responsible for more general age-related declines in associative learning and memory. The evidence for this model is briefly reviewed and studies suggesting age-related effects on classical conditioning of various response systems are described within the context of the brain structures implicated by the model.

  9. Experimental challenges to theories of classical conditioning: application of an attentional model of storage and retrieval.

    Science.gov (United States)

    Schmajuk, Nestor A; Larrauri, José A

    2006-01-01

    Several studies have recently challenged the accuracy of traditional models of classical conditioning that account for some experimental data in terms of a storage deficit. Among other results, it has been reported that extinction of the blocking or overshadowing stimulus results in the recovery of the response to the blocked or overshadowed stimulus, backward blocking shows spontaneous recovery, extinction of the training context results in the recovery from latent inhibition, interposing a delay between conditioning and testing in latent inhibition increases latent inhibition, and latent inhibition antagonizes overshadowing. An existing neural network model of classical conditioning (N. A. Schmajuk, Y. Lam, & J. A. Gray, 1996), which includes an attentional mechanism controlling both storage and retrieval of associations, is able to quantitatively describe these results.

  10. Psychiatric Conditions in Parkinson Disease: A Comparison With Classical Psychiatric Disorders.

    Science.gov (United States)

    Buoli, Massimiliano; Caldiroli, Alice; Altamura, Alfredo Carlo

    2016-03-01

    Psychiatric conditions often complicate the outcome of patients affected by Parkinson disease (PD), but they differ from classical psychiatric disorders in terms of underlying biological mechanisms, clinical presentation, and treatment response. The purpose of the present review is to illustrate the biological and clinical aspects of psychiatric conditions associated with PD, with particular reference to the differences with respect to classical psychiatric disorders. A careful search of articles on main databases was performed in order to obtain a comprehensive review about the main psychiatric conditions associated with PD. A manual selection of the articles was then performed in order to consider only those articles that concerned with the topic of the review. Psychiatric conditions in patients with PD present substantial differences with respect to classical psychiatric disorders. Their clinical presentation does not align with the symptom profiles represented by Diagnostic and Statistical Manual for Mental Disorders and International Classification of Diseases. Furthermore, psychiatry treatment guidelines are of poor help in managing psychiatric symptoms of patients with PD. Specific diagnostic tools and treatment guidelines are needed to allow early diagnosis and adequate treatment of psychiatric conditions in comorbidity with PD.

  11. Avoidant symptoms in PTSD predict fear circuit activation during multimodal fear extinction.

    Science.gov (United States)

    Sripada, Rebecca K; Garfinkel, Sarah N; Liberzon, Israel

    2013-01-01

    Convergent evidence suggests that individuals with posttraumatic stress disorder (PTSD) exhibit exaggerated avoidance behaviors as well as abnormalities in Pavlonian fear conditioning. However, the link between the two features of this disorder is not well understood. In order to probe the brain basis of aberrant extinction learning in PTSD, we administered a multimodal classical fear conditioning/extinction paradigm that incorporated affectively relevant information from two sensory channels (visual and tactile) while participants underwent fMRI scanning. The sample consisted of fifteen OEF/OIF veterans with PTSD. In response to conditioned cues and contextual information, greater avoidance symptomatology was associated with greater activation in amygdala, hippocampus, vmPFC, dmPFC, and insula, during both fear acquisition and fear extinction. Heightened responses to previously conditioned stimuli in individuals with more severe PTSD could indicate a deficiency in safety learning, consistent with PTSD symptomatology. The close link between avoidance symptoms and fear circuit activation suggests that this symptom cluster may be a key component of fear extinction deficits in PTSD and/or may be particularly amenable to change through extinction-based therapies.

  12. Fear Generalization in Humans: Systematic Review and Implications for Anxiety Disorder Research.

    Science.gov (United States)

    Dymond, Simon; Dunsmoor, Joseph E; Vervliet, Bram; Roche, Bryan; Hermans, Dirk

    2015-09-01

    Fear generalization, in which conditioned fear responses generalize or spread to related stimuli, is a defining feature of anxiety disorders. The behavioral consequences of maladaptive fear generalization are that aversive experiences with one stimulus or event may lead one to regard other cues or situations as potential threats that should be avoided, despite variations in physical form. Theoretical and empirical interest in the generalization of conditioned learning dates to the earliest research on classical conditioning in nonhumans. Recently, there has been renewed focus on fear generalization in humans due in part to its explanatory power in characterizing disorders of fear and anxiety. Here, we review existing behavioral and neuroimaging empirical research on the perceptual and non-perceptual (conceptual and symbolic) generalization of fear and avoidance in healthy humans and patients with anxiety disorders. The clinical implications of this research for understanding the etiology and treatment of anxiety is considered and directions for future research described.

  13. Conditional symmetries in axisymmetric quantum cosmologies with scalar ?elds and the fate of the classical singularities

    CERN Document Server

    Zampeli, Adamantia; Terzis, Petros A; Christodoulakis, T

    2015-01-01

    In this paper, the classical and quantum solutions of some axisymmetric cosmologies coupled to a massless scalar field are studied in the context of minisuperspace approximation. In these models, the singular nature of the Lagrangians entails a search for possible conditional symmetries. These have been proven to be the simultaneous conformal symmetries of the supermetric and the superpotential. The quantization is performed by adopting the Dirac proposal for constrained systems, i.e. promoting the first-class constraints to operators annihilating the wave function. To further enrich the approach, we follow \\cite{Christodoulakis:2012eg} and impose the operators related to the classical conditional symmetries on the wave function. These additional equations select particular solutions of the Wheeler-DeWitt equation. In order to gain some physical insight from the quantization of these cosmological systems, we perform a semiclassical analysis following the Bohmian approach to quantum theory. The generic result ...

  14. Rabbit cerebellar slice analysis of long-term depression and its role in classical conditioning.

    Science.gov (United States)

    Schreurs, B G; Alkon, D L

    1993-12-24

    Cerebellar long-term depression (LTD) has been proposed as a mechanism underlying classical conditioning of the rabbit nictitating membrane/eyelid response (NMR). However, LTD has only been obtained reliably when (1) cerebellar slices are bathed in GABA antagonists which abolish disynaptic inhibitory post synaptic potentials, and (2) the temporal sequence of stimulation used in slice or intact preparations is the opposite of that used in classical conditioning. Based on intradendritic Purkinje cell recordings obtained from rabbit cerebellar slices, we report that stimulation of climbing fibers and then parallel fibers in the presence of the GABA antagonist, bicuculline, produced significant depression of parallel fiber excitatory post synaptic potential (epsp) amplitude that continued to increase for at least 20 min after stimulation. However, application of the same stimulation protocol without GABA antagonists produced a brief depression of parallel fiber epsps that disappeared within minutes. Activation of parallel fibers and then climbing fibers in an order opposite to the LTD-producing sequence (i.e. a classical conditioning-like order) produced a brief depression that dissipated quickly. Stimulation of parallel fibers alone produced a small, slowly developing potentiation, but stimulation of parallel fibers during depolarization-induced local dendritic calcium spikes produced significant depression almost immediately which then declined slowly to more modest levels. Finally, stimulation of parallel fibers at frequencies used in in vivo parallel fiber-climbing fiber stimulation experiments (e.g. 100 Hz) produced an immediate and profound long-lasting epsp depression. The depression occurred, however, whether parallel and climbing fibers were stimulated separately (unpaired) or in a classical conditioning-like protocol (paired) where parallel fiber stimulation coterminated with climbing fiber stimulation (10 Hz).(ABSTRACT TRUNCATED AT 250 WORDS)

  15. Fear of falling is associated with prolonged anticipatory postural adjustment during gait initiation under dual-task conditions in older adults.

    Science.gov (United States)

    Uemura, Kazuki; Yamada, Minoru; Nagai, Koutatsu; Tanaka, Buichi; Mori, Shuhei; Ichihashi, Noriaki

    2012-02-01

    Little is known about dynamic balance control under dual-task conditions in older adults with fear of falling (FoF). The purpose of this study was to examine the effect of FoF on anticipatory postural adjustment (APA) during gait initiation under dual-task conditions in older adults. Fifty-seven elderly volunteers (age, 79.2 [6.8] years) from the community participated in this study. Each participant was categorised into either the Fear (n=24) or No-fear (n=33) group on the basis of the presence or absence of FoF. Under single- and dual-task conditions, centre of pressure (COP) data were collected while the participants performed gait initiation trials from a starting position on a force platform. We also performed a 10-m walking test (WT), a timed up & go test (TUG), and a functional reach test (FR). The reaction and APA phases were measured from the COP data. The results showed that under the dual-task condition, the Fear group had significantly longer APA phases than the No-fear group, although no significant differences were observed between the 2 groups in the reaction and APA phases under the single-task condition and in any clinical measurements (WT, TUG, and FR). Our findings suggest that specific deficits in balance control occur in subjects with FoF during gait initiation while dual tasking, even if their physical functions are comparable to subjects without FoF.

  16. Contingency awareness shapes acquisition and extinction of emotional responses in a conditioning model of pain-related fear

    Directory of Open Access Journals (Sweden)

    Franziska eLabrenz

    2015-11-01

    Full Text Available As a fundamental learning process, fear conditioning promotes the formation of associations between predictive cues and biologically-significant signals. In its application to pain, conditioning may provide important insight into mechanisms underlying pain-related fear, although knowledge especially in interoceptive pain paradigms remains scarce. Furthermore, while the influence of contingency awareness on excitatory learning is subject of ongoing debate, its role in pain-related acquisition is poorly understood and essentially unknown regarding extinction as inhibitory learning. Therefore, we addressed the impact of contingency awareness on learned emotional responses to pain- and safety-predictive cues in a combined dataset of two pain-related conditioning studies.In total, 75 healthy participants underwent differential fear acquisition, during which rectal distensions as interoceptive unconditioned stimuli (US were repeatedly paired with a predictive visual cue (conditioned stimulus; CS+ while another cue (CS- was presented unpaired. During extinction, both CS were presented without US. CS valence, indicating learned emotional responses, and CS-US contingencies were assessed on visual analogue scales. Based on an integrative measure of contingency accuracy, a median-split was performed to compare groups with low versus high contingency accuracy regarding learned emotional responses. To investigate predictive value of contingency accuracy, regression analyses were conducted. Highly accurate individuals revealed more pronounced negative emotional responses to CS+ and increased positive responses to CS- when compared to participants with low contingency accuracy. Following extinction, highly accurate individuals had fully extinguished pain-predictive cue properties, while exhibiting persistent positive emotional responses to safety signals. In contrast, individuals with low accuracy revealed equally positive emotional responses to both, CS+ and

  17. Transsynaptic EphB/Ephrin-B signaling regulates growth of presynaptic boutons required for classical conditioning.

    Science.gov (United States)

    Li, Wei; Zheng, Zhaoqing; Keifer, Joyce

    2011-06-01

    Learning-related presynaptic remodeling has been documented in only a few systems, and its molecular mechanisms are largely unknown. Here we describe a role for the bidirectional EphB/ephrin-B signaling system in structural plasticity of presynaptic nerve terminals using an in vitro model of classical conditioning. Conditioning or BDNF application induced significant growth of auditory nerve presynaptic boutons that convey the conditioned stimulus to abducens motor neurons. Interestingly, bouton enlargement occurred only for those synapses apposed to motor neuron dendrites rather than to somata. Phosphorylation of ephrin-B1, but not EphB2, was induced by both conditioning and BDNF application and was inhibited by postsynaptic injections of ephrin-B antibody. Finally, suppression of postsynaptic ephrin-B function inhibited presynaptic bouton enlargement that was rescued by activation of EphB2 by ephrin-B1-Fc. These data provide evidence for ephrin-B-induced EphB2 forward signaling in presynaptic structural plasticity during classical conditioning. They also reveal a functional interaction between BDNF/TrkB and the Eph/ephrin signaling systems in the coordination of presynaptic and postsynaptic modifications during conditioning.

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

    DEFF Research Database (Denmark)

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

    in fishes. Here we show that the omission of expected reward (OER) leads to increased aggression towards conspecifics in classically conditioned Atlantic salmon (Salmo salar). Furthermore, in response to an acute stressor, OER fish displayed increased dopaminergic (DA) neurotransmission compared to controls....... There was also a general downregulation of dopamine receptor D1 gene expression in the telencephalon of OER groups, which suggests a coping mechanism in response to unbalanced DA metabolism. These results indicate that animals subjected to unpredictable reward conditions develop a senzitation of the DA...

  19. Psychology of the scientist: LXXXII. Coverage of classical conditioning in textbooks in the psychology of learning, 1952-1995.

    Science.gov (United States)

    Coleman, S R; Fanelli, A; Gedeon, S

    2000-06-01

    Objective information was obtained from 89 textbooks in the psychology of learning published from 1952 through 1995 to answer questions about their coverage of classical conditioning. We found (a) that classical conditioning consistently received less coverage than instrumental and operant conditioning, (b) that the distinction of classical and instrumental conditioning has become established as a textbook-construction device, (c) that use of the classical-instrumental distinction by textbook authors has "hardened" after a period of "fluidity" in the 1970s, (d) that the currency of references in the basic classical (as well as instrumental) conditioning chapters diminished from 1952 to 1995. Findings are discussed in regard to the possibility that, as a class, and in comparison to other textbooks, the textbooks of the psychology of learning fall short of fulfilling some of their recognized roles.

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

    CERN Document Server

    Shirokov, M E

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Hiroyuki Toda

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

  2. Concentration- and age-dependent effects of chronic caffeine on contextual fear conditioning in C57BL/6J mice.

    Science.gov (United States)

    Poole, Rachel L; Braak, David; Gould, Thomas J

    2016-02-01

    Chronic caffeine exerts negligible effects on learning and memory in normal adults, but it is unknown whether this is also true for children and adolescents. The hippocampus, a brain region important for learning and memory, undergoes extensive structural and functional modifications during pre-adolescence and adolescence. As a result, chronic caffeine may have differential effects on hippocampus-dependent learning in pre-adolescents and adolescents compared with adults. Here, we characterized the effects of chronic caffeine and withdrawal from chronic caffeine on hippocampus-dependent (contextual) and hippocampus-independent (cued) fear conditioning in pre-adolescent, adolescent, and adult mice. The results indicate that chronic exposure to caffeine during pre-adolescence and adolescence enhances or impairs contextual conditioning depending on concentration, yet has no effect on cued conditioning. In contrast, withdrawal from chronic caffeine impairs contextual conditioning in pre-adolescent mice only. No changes in learning were seen for adult mice for either the chronic caffeine or withdrawal conditions. These findings support the hypothesis that chronic exposure to caffeine during pre-adolescence and adolescence can alter learning and memory and as changes were only seen in hippocampus-dependent learning, which suggests that the developing hippocampus may be sensitive to the effects of caffeine.

  3. The GABA(B) receptor positive modulator BHF177 attenuated anxiety, but not conditioned fear, in rats.

    Science.gov (United States)

    Li, Xia; Kaczanowska, Katarzyna; Finn, M G; Markou, Athina; Risbrough, Victoria B

    2015-10-01

    GABAB (γ-aminobutyric acid B) receptors may be a therapeutic target for anxiety disorders. Here we characterized the effects of the GABAB receptor positive allosteric modulator (PAM) BHF177 on conditioned and unconditioned physiological responses to threat in the light-enhanced startle (LES), stress-induced hyperthermia, and fear-potentiated startle (FPS) procedures in rats. The effects of BHF177 on LES were compared with those of the GABAB receptor agonists baclofen and CGP44532, and the positive control buspirone, a 5-HT1A receptor partial agonist with anxiolytic activity in humans. Baclofen (0.4, 0.9 and 1.25 mg/kg) and CGP44532 (0.065, 0.125 and 0.25 mg/kg) administration had significant sedative, but not anxiolytic, activity reflected in overall decrease in the startle response in the LES tests. BHF177 (10, 20 and 40 mg/kg) had no effect on LES, nor did it produce an overall sedative effect. Interesting, however, when rats were grouped by high and low LES responses, BHF177 had anxiolytic-like effects only on LES in high, but not low, LES responding rats. BHF177 also blocked stress-induced hyperthermia, but had no effect on conditioned fear responses in the FPS test. Buspirone (1 and 3 mg/kg) had an anxiolytic-like profile in both LES and FPS tests. These results indicate that BHF177 may specifically attenuate unconditioned anxiety in individuals that exhibit a high anxiety state, and has fewer sedative effects than direct agonists. Thus, BHF177 or other GABAB receptor PAMs may be promising compounds for alleviating increased anxiety seen in various psychiatric disorders with a superior side-effect profile compared to GABAB receptor agonists.

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

    Science.gov (United States)

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

    2009-01-01

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

  5. Role of NPY Y1 receptor on acquisition, consolidation and extinction on contextual fear conditioning: dissociation between anxiety, locomotion and non-emotional memory behavior.

    Science.gov (United States)

    Lach, Gilliard; de Lima, Thereza Christina Monteiro

    2013-07-01

    Neuropeptide Y (NPY) is the most abundant peptide in the central nervous system (CNS) and is densely localized in the brain regions involved in stress, memory, fear and anxiety. Although previous research supports a role for NPY in the mediation of rodent and human emotional behavior, there is currently a lack of information on the effects of low doses of NPY that could have a potential therapeutic advantage, minimizing side-effects such as cognition impairment or sedation. Herein, we assessed the effects of intracerebroventricular (i.c.v.) administration of low doses of NPY, and of the Y1-agonist Leu31Pro34-NPY (LP-NPY) on contextual fear conditioning (CFC), as they have no effect on unconditioned anxiety-like, locomotor activity and non-emotional memory. NPY (3 pmol) and LP-NPY (1 pmol) inhibited freezing behavior when administered in the acquisition or consolidation stages, indicating a reduction of fear. When injected in the extinction phase, only NPY inhibited freezing behavior on CFC. Pre-treatment with the Y1-antagonist BIBO3304 before NPY and LP-NPY was able to prevent the inhibition of fear responses induced by both NPY agonists. Taken together, our results demonstrate robust fear-inhibiting effects of i.c.v. injection of NPY on contextual fear conditioning in rats, a response that is mediated, at least in part, by the Y1 receptor. Moreover, these treatments were unable to change locomotor activity or to show an anxiolytic-like effect, as evaluated in an open-field and an elevated plus-maze. This specific fear reduction effect may underlie resilience systems in the CNS and has potential therapeutic relevance in PTSD.

  6. Classical Conditioning Components of the Orienting Reflex to Words Using Innocuous and Noxious Unconditioned Stimuli Under Different Conditioned Stimulus-Unconditioned Stimulus Intervals

    Science.gov (United States)

    Maltzman, Irving; And Others

    1977-01-01

    Concerns the examination of conditioned stimulus--unconditioned stimulus (CS--UCS) intervals of different lengths. Demonstrates the feasibility of using a forewarned reaction time procedure with an innocuous imperative stimulus for the investigation of classical conditioning. (Editor/RK)

  7. Dorsolateral periaqueductal gray matter CB1 and TRPV1 receptors exert opposite modulation on expression of contextual fear conditioning.

    Science.gov (United States)

    Uliana, D L; Hott, S C; Lisboa, S F; Resstel, L B M

    2016-04-01

    Cannabinoid type 1 (CB1) and Transient Potential Vanilloid type 1 (TRPV1) receptors in the dorsolateral periaqueductal gray (dlPAG) matter are involved in the modulation of conditioned response. Both CB1 and TRPV1 receptors are related to glutamate release and nitric oxide (NO) synthesis. It was previously demonstrated that both NMDA glutamate receptors and NO are involved in the conditioned emotional response. Therefore, one aim of this work was to verify whether dlPAG CB1 and TRPV1 receptors modulate the expression of contextual conditioned emotional response. Moreover, we also investigated the involvement of NMDA receptors and the NO pathway in this response. Male Wistar rats with local dlPAG guide cannula were submitted to contextual fear conditioning. Following 24 h, a polyethylene catheter was implanted in the femoral artery for cardiovascular recordings. After an additional 24 h, drugs were administered in the dlPAG and freezing behavior and autonomic responses were recorded during chamber re-exposure. Both a CB1 antagonist (AM251) and a TRPV1 agonist (Capsaicin; CPS) increased the expression of a conditioned emotional response. This response was prevented by an NMDA antagonist, a preferential neuronal NO synthase inhibitor, an NO scavenger and a soluble guanylate cyclase inhibitor (sGC). Furthermore, pretreatment with a TRPV1 antagonist also prevented the increased conditioned emotional response induced by AM251. Considering that GABA can counterbalance glutamate effects, we also investigated whether GABAA receptors were involved in the effect of a higher dose of AM251. Pretreatment with a GABAA receptor antagonist caused an increased conditioned emotional response by AM251. Our results support the possibility that dlPAG CB1 and TRPV1 receptors are involved in the expression of conditioned emotional response through the NMDA/NO/sGC pathway. Moreover, the opposite effects exerted by GABA and glutamate could produce different outcomes of drugs modulating eCBs.

  8. Further evidence for involvement of the dorsal hippocampus serotonergic and γ-aminobutyric acid (GABA)ergic pathways in the expression of contextual fear conditioning in rats.

    Science.gov (United States)

    Almada, Rafael C; Albrechet-Souza, Lucas; Brandão, Marcus L

    2013-12-01

    Intra-dorsal hippocampus (DH) injections of 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), a serotonin-1A (5-hydroxytryptamine (5-HT)-1A) receptor agonist, were previously shown to inhibit the expression of contextual fear when administered six hours after conditioning. However, further understanding of the consolidation and expression of aversive memories requires investigations of these and other mechanisms at distinct time points and the regions of the brain to which they are transferred. Thus, the purpose of the present study was to investigate the role of DH serotonergic and γ-aminobutyric acid (GABA)ergic mechanisms in the expression of contextual fear 24 h after conditioning, reflected by fear-potentiated startle (FPS) and freezing behavior. The recruitment of the amygdala and medial prefrontal cortex (mPFC) in these processes was also evaluated by measuring Fos protein immunoreactivity. Although intra-DH injections of 8-OH-DPAT did not produce behavioral changes, muscimol reduced both FPS and the freezing response. Fos protein immunoreactivity revealed that contextual fear promoted wide activation of the mPFC, which was significantly reduced after intra-DH infusions of muscimol. The present findings, together with previous data, indicate that in contrast to 5-HT, which appears to play a role during the early phases of contextual aversive memory consolidation, longer-lasting GABA-mediated mechanisms are recruited during the expression of contextual fear memories.

  9. Intraperitoneal sertraline and fluvoxamine increase contextual fear conditioning but are without effect on overshadowing between cues.

    Science.gov (United States)

    Cassaday, H J; Thur, K E

    2015-02-01

    Treatment with selective serotonin reuptake inhibitors (SSRIs) can reduce contextual conditioning. Since contexts comprise a variety of potentially competing cues, impaired overshadowing may provide an account of such effects. The present study therefore compared the effects of two SSRIs on overshadowing and contextual conditioning, testing suppression of an ongoing behavioral response (licking) by cues previously paired with foot shock. Conditioning to a 5 s light stimulus was reduced when it was presented in compound with a 5 s noise, thus overshadowing was demonstrated. In two experiments, this overshadowing was unaffected by treatment with either sertraline or fluvoxamine. However, unconditioned suppression to the noise (tested in a control group previously conditioned to the light alone) was reduced after sertraline (10 mg/kg, i.p.). The successful demonstration of overshadowing required the use of a second conditioning session or an additional conditioning trial within the same conditioning session. Neither weak nor strong overshadowing (of the light by the tone) was affected by any drug treatment. Moreover, counter to prediction, conditioning to contextual cues was increased rather than impaired by treatment with sertraline (10 mg/kg, i.p.) and fluvoxamine (30 mg/kg, i.p.).

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

    Science.gov (United States)

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

    2008-01-01

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

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

    NARCIS (Netherlands)

    D. Sevenster; T. Beckers; M. Kindt

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Simone B Sartori

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

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

    Directory of Open Access Journals (Sweden)

    Reis F.

    1999-01-01

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

  14. Frozen with fear: Conditioned suppression in a virtual reality model of human anxiety.

    Science.gov (United States)

    Allcoat, Devon; Greville, W James; Newton, Philip M; Dymond, Simon

    2015-09-01

    Freezing-like topographies of behavior are elicited in conditioned suppression tasks whereby appetitive behavior is reduced by presentations of an aversively conditioned threat cue relative to a safety cue. Conditioned suppression of operant behavior by a Pavlovian threat cue is an established laboratory model of quantifying the response impairment seen in anxiety disorders. Little is known however about how different response topographies indicative of conditioned suppression are elicited in humans. Here, we refined a novel virtual reality (VR) paradigm in which presentations of a threat cue of unpredictable duration occurred while participants performed an operant response of shooting and destroying boxes searching for hidden gold. The VR paradigm detected significant suppression of response topographies (shots, hits and breaks) for a Pavlovian threat cue relative to a safety cue and novel cue presentations. Implications of the present findings for translational research on appetitive and aversive conflict in anxiety disorders are discussed.

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

    Science.gov (United States)

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

    2016-05-01

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

  16. Facilitated acquisition of standard but not long delay classical eyeblink conditioning in behaviorally inhibited adolescents.

    Science.gov (United States)

    Caulfield, M D; VanMeenen, K M; Servatius, R J

    2015-02-01

    Adolescence is a key age in the development of anxiety disorders. The present study assessed the relationship between behavioral inhibition, a risk factor for anxiety typified by avoidance, and acquisition of the classically conditioned eyeblink response. 168 healthy high school students (mean age 15.7 years, 54% female) were given a battery of self-report measures including the Adult Measure of Behavioural Inhibition (AMBI). The study compared acquisition of three experimental training conditions. Two groups were given paired CS-US training: standard delay of 500-ms or long delay of 1000-ms with CS overlapping and co-terminating with a 50-ms airpuff US. A third group received unpaired training of 1000-ms CS and 50-ms airpuff US. Inhibited individuals showed greater acquisition of the conditioned eyeblink response in the 500-ms CS condition, but not in the paired 1000-ms condition. No differences in spontaneous blinks or reactivity to the stimulus were evident in the 1000-ms unpaired CS condition. Results support a relationship between associative learning and anxiety vulnerability that may be mediated by cerebellar functioning in inhibited individuals.

  17. Novelty-Induced Arousal Enhances Memory for Cued Classical Fear Conditioning: Interactions between Peripheral Adrenergic and Brainstem Glutamatergic Systems

    Science.gov (United States)

    King, Stanley O., II; Williams, Cedric L.

    2009-01-01

    Exposure to novel contexts produce heightened states of arousal and biochemical changes in the brain to consolidate memory. However, processes permitting simple exposure to unfamiliar contexts to elevate sympathetic output and to improve memory are poorly understood. This shortcoming was addressed by examining how novelty-induced changes in…

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

    Science.gov (United States)

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

    2012-01-01

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

  19. Immunomodulation by classical conditioning in NZB/W (F1) mice: Lifespan and diurnal variation

    Science.gov (United States)

    Miguel, Mario André Leocadio; Menna-Barreto, Luiz

    2016-01-01

    Systemic Lupus Eritematosus (SLE) is a systemic inflammatory disease often treated with the agent cyclophosphamide (CY), known by provoking important adverse reactions to the organism. Ader and Cohen have demonstrated an alternative way of administrating this agent based on pavlovian conditioning, in order to reduce the aggression caused by CY. Considering the influence of the temporal organization on learning and memory processes, the purpose of this study was to understand the temporal aspects involved in the conditioned immunomodulation. In a search for circadian modulation, we selected NZB/W (F1) female mice, a strain that spontaneously develop SLE. Divided into two major groups, the animals were submitted, in different phases of day, to a classical conditioning immunomodulation protocol, consisting in weekly parings of saccharin solution and CY injections. The success of the paradigm was evaluated by comparing lifespan among the groups. Simultaneously, it was monitored the water intake behavior, in order to correlate the stability of two rhythmic parameters, amplitude and spectral power density of the 24-h rhythm, with the progression of SLE. Our results indicate that mice could benefit from the conditioning task performed either in the light phase or in the dark phase of the LD cycle, as expressed by an increased lifespan. Concerning the rhythmic parameters, there was evidence of association between the rhythmic stability and the evolution of SLE, demonstrated by the maintenance of healthy levels of amplitude and spectral potency of the 24-h rhythm in animals exposed to the conditioning paradigm. PMID:27226820

  20. Experimental Evidence of Classical Conditioning and Microscopic Engrams in an Electroconductive Material

    Science.gov (United States)

    Karbowski, Lukasz M.; Persinger, Michael A.

    2016-01-01

    Synthetic experimental substrates are indispensable tools which can allow researchers to model biological processes non-invasively in three-dimensional space. In this study, we investigated the capacities of an electroconductive material whose properties converge upon those of the brain. An electrically conductive material composed of carbohydrates, proteins, fats, ions, water, and trace amounts of other organic compounds and minerals was classically conditioned as inferred by electrophysiological measurements. Spectral densities evoked during the display of a conditioned stimulus (CS) probe were strongly congruent with those displayed during the conditioned-unconditioned stimulus pairing (CS-UCS). The neutral stimulus consisted of the pulsed light from a LED. The unconditioned stimulus was an alternating current. Interstimulus intervals >130 ms did not result in conditioned responses. Microscopic analysis of the chemically-fixed substratum revealed 10–200 μm wide ‘vessel structures’ within samples exposed to a stimulus. Greater complexity (increased fractal dimensions) was clearly discernable by light microscopy for stained sections of fixed samples that had been conditioned compared to various controls. The denser pixels indicated greater concentration of stain and increased canalization. Implications for learning and memory formation are discussed. PMID:27764215

  1. GABA(A) receptor activation in the CA1 area of the dorsal hippocampus impairs consolidation of conditioned contextual fear in C57BL/6J mice.

    Science.gov (United States)

    Misane, Ilga; Kruis, Ayla; Pieneman, Anton W; Ögren, Sven Ove; Stiedl, Oliver

    2013-02-01

    Local infusion of the GABA(A) receptor agonist muscimol is used for reversible inactivation of septohippocampal brain structures associated with cognitive functions. However, information on the effective duration, affected processes and site(s) of action of muscimol in the hippocampus is lacking. Therefore, the dose- and time-dependent effects of bilateral dorsohippocampal infusion of muscimol (0.01-2.0 μg/mouse) below the CA1 area were examined on processing of fear memory in male C57BL/6J mice. Infusion of muscimol 15 min-6 h but not 9 h or 24 h before training impaired conditioned context-dependent fear tested 24 h or 48 h after training. Post-training infusion of muscimol also impaired context-dependent fear when applied either 4 h or 6 h after training, although with lower efficacy. Muscimol was ineffective when administered immediately, 1 h or 24 h after training. Infusion of muscimol 15 min before training impaired context-dependent fear 4-6 h after training indicating preserved short-term but impaired long-term memory. Regardless of infusion time and dose, muscimol had no effect on tone-dependent (cued) fear memory. The impairment by the fluorescently-labeled muscimol-bodipy (5.3 μg/mouse) were similar to those of an equimolar dose of muscimol (1 μg/mouse). The distribution profile after local infusion indicated that muscimol-bodipy (5.3 μg/mouse) was confined to the CA1 area of the dorsal hippocampus. These results demonstrated that GABA(A) receptor activation in the CA1 area of the dorsal hippocampus causes a long-term memory impairment of conditioned context-dependent fear mediated by a long-lasting (≥6 h) muscimol action most likely affecting consolidation processes.

  2. Weaving the (neuronal) web: fear learning in spider phobia.

    Science.gov (United States)

    Schweckendiek, Jan; Klucken, Tim; Merz, Christian J; Tabbert, Katharina; Walter, Bertram; Ambach, Wolfgang; Vaitl, Dieter; Stark, Rudolf

    2011-01-01

    Theories of specific phobias consider classical conditioning as a central mechanism in the pathogenesis and maintenance of the disorder. Although the neuronal network underlying human fear conditioning is understood in considerable detail, no study to date has examined the neuronal correlates of fear conditioning directly in patients with specific phobias. Using functional magnet resonance imaging (fMRI) we investigated conditioned responses using phobia-relevant and non-phobia-relevant unconditioned stimuli in patients with specific phobias (n=15) and healthy controls (n=14) by means of a differential picture-picture conditioning paradigm: three neutral geometric figures (conditioned stimuli) were followed by either pictures of spiders, highly aversive scenes or household items (unconditioned stimuli), respectively. Enhanced activations within the fear network (medial prefrontal cortex, anterior cingulate cortex, amygdala, insula and thalamus) were observed in response to the phobia-related conditioned stimulus. Further, spider phobic subjects displayed higher amygdala activation in response to the phobia-related conditioned stimulus than to the non-phobia-related conditioned stimulus. Moreover, no differences between patients and healthy controls emerged regarding the non-phobia-related conditioned stimulus. The results imply that learned phobic fear is based on exaggerated responses in structures belonging to the fear network and emphasize the importance of the amygdala in the processing of phobic fear. Further, altered responding of the fear network in patients was only observed in response to the phobia-related conditioned stimulus but not to the non-phobia-related conditioned stimulus indicating no differences in general conditionability between patients with specific phobias and healthy controls.

  3. APPLICATION OF PREMACK’S THEORY TO A CLASSICALLY CONDITIONED SUCROSE AVERSION INDUCED BY X-RAY EXPOSURE,

    Science.gov (United States)

    for the applicability to classical conditioning of Premack’s reinforcement theory in which the rate of reinforced responding is determined in part by the precontingency rate of the response. (Author)

  4. The Genetic Absence Epilepsy Rats from Strasbourg model of absence epilepsy exhibits alterations in fear conditioning and latent inhibition consistent with psychiatric comorbidities in humans.

    Science.gov (United States)

    Marks, Wendie N; Cavanagh, Mary E; Greba, Quentin; Cain, Stuart M; Snutch, Terrance P; Howland, John G

    2016-01-01

    Behavioural, neurological, and genetic similarities exist in epilepsies, their psychiatric comorbidities, and various psychiatric illnesses, suggesting common aetiological factors. Rodent models of epilepsy are used to characterize the comorbid symptoms apparent in epilepsy and their neurobiological mechanisms. The present study was designed to assess Pavlovian fear conditioning and latent inhibition in a polygenetic rat model of absence epilepsy, i.e. Genetic Absence Epilepsy Rats from Strasbourg (GAERS) and the non-epileptic control (NEC) strain. Electrophysiological recordings confirmed the presence of spike-wave discharges in young adult GAERS but not NEC rats. A series of behavioural tests designed to assess anxiety-like behaviour (elevated plus maze, open field, acoustic startle response) and cognition (Pavlovian conditioning and latent inhibition) was subsequently conducted on male and female offspring. Results showed that GAERS exhibited significantly higher anxiety-like behaviour, a characteristic reported previously. In addition, using two protocols that differed in shock intensity, we found that both sexes of GAERS displayed exaggerated cued and contextual Pavlovian fear conditioning and impaired fear extinction. Fear reinstatement to the conditioned stimuli following unsignalled footshocks did not differ between the strains. Male GAERS also showed impaired latent inhibition in a paradigm using Pavlovian fear conditioning, suggesting that they may have altered attention, particularly related to previously irrelevant stimuli in the environment. Neither the female GAERS nor NEC rats showed evidence of latent inhibition in our paradigm. Together, the results suggest that GAERS may be a particularly useful model for assessing therapeutics designed to improve the emotional and cognitive disturbances associated with absence epilepsy.

  5. Deletion of glutamate delta-1 receptor in mouse leads to enhanced working memory and deficit in fear conditioning.

    Science.gov (United States)

    Yadav, Roopali; Hillman, Brandon G; Gupta, Subhash C; Suryavanshi, Pratyush; Bhatt, Jay M; Pavuluri, Ratnamala; Stairs, Dustin J; Dravid, Shashank M

    2013-01-01

    Glutamate delta-1 (GluD1) receptors are expressed throughout the forebrain during development with high levels in the hippocampus during adulthood. We have recently shown that deletion of GluD1 receptor results in aberrant emotional and social behaviors such as hyperaggression and depression-like behaviors and social interaction deficits. Additionally, abnormal expression of synaptic proteins was observed in amygdala and prefrontal cortex of GluD1 knockout mice (GluD1 KO). However the role of GluD1 in learning and memory paradigms remains unknown. In the present study we evaluated GluD1 KO in learning and memory tests. In the eight-arm radial maze GluD1 KO mice committed fewer working memory errors compared to wildtype mice but had normal reference memory. Enhanced working memory in GluD1 KO was also evident by greater percent alternation in the spontaneous Y-maze test. No difference was observed in object recognition memory in the GluD1 KO mice. In the Morris water maze test GluD1 KO mice showed no difference in acquisition but had longer latency to find the platform in the reversal learning task. GluD1 KO mice showed a deficit in contextual and cue fear conditioning but had normal latent inhibition. The deficit in contextual fear conditioning was reversed by D-Cycloserine (DCS) treatment. GluD1 KO mice were also found to be more sensitive to foot-shock compared to wildtype. We further studied molecular changes in the hippocampus, where we found lower levels of GluA1, GluA2 and GluK2 subunits while a contrasting higher level of GluN2B in GluD1 KO. Additionally, we found higher postsynaptic density protein 95 (PSD95) and lower glutamate decarboxylase 67 (GAD67) expression in GluD1 KO. We propose that GluD1 is crucial for normal functioning of synapses and absence of GluD1 leads to specific abnormalities in learning and memory. These findings provide novel insights into the role of GluD1 receptors in the central nervous system.

  6. Deletion of glutamate delta-1 receptor in mouse leads to enhanced working memory and deficit in fear conditioning.

    Directory of Open Access Journals (Sweden)

    Roopali Yadav

    Full Text Available Glutamate delta-1 (GluD1 receptors are expressed throughout the forebrain during development with high levels in the hippocampus during adulthood. We have recently shown that deletion of GluD1 receptor results in aberrant emotional and social behaviors such as hyperaggression and depression-like behaviors and social interaction deficits. Additionally, abnormal expression of synaptic proteins was observed in amygdala and prefrontal cortex of GluD1 knockout mice (GluD1 KO. However the role of GluD1 in learning and memory paradigms remains unknown. In the present study we evaluated GluD1 KO in learning and memory tests. In the eight-arm radial maze GluD1 KO mice committed fewer working memory errors compared to wildtype mice but had normal reference memory. Enhanced working memory in GluD1 KO was also evident by greater percent alternation in the spontaneous Y-maze test. No difference was observed in object recognition memory in the GluD1 KO mice. In the Morris water maze test GluD1 KO mice showed no difference in acquisition but had longer latency to find the platform in the reversal learning task. GluD1 KO mice showed a deficit in contextual and cue fear conditioning but had normal latent inhibition. The deficit in contextual fear conditioning was reversed by D-Cycloserine (DCS treatment. GluD1 KO mice were also found to be more sensitive to foot-shock compared to wildtype. We further studied molecular changes in the hippocampus, where we found lower levels of GluA1, GluA2 and GluK2 subunits while a contrasting higher level of GluN2B in GluD1 KO. Additionally, we found higher postsynaptic density protein 95 (PSD95 and lower glutamate decarboxylase 67 (GAD67 expression in GluD1 KO. We propose that GluD1 is crucial for normal functioning of synapses and absence of GluD1 leads to specific abnormalities in learning and memory. These findings provide novel insights into the role of GluD1 receptors in the central nervous system.

  7. Interoceptive fear conditioning as a learning model of panic disorder: an experimental evaluation using 20% CO(2)-enriched air in a non-clinical sample.

    Science.gov (United States)

    Acheson, Dean T; Forsyth, John P; Prenoveau, Jason M; Bouton, Mark E

    2007-10-01

    Despite the role afforded interoceptive fear conditioning in etiologic accounts of panic disorder, there are no good experimental demonstrations of such learning in humans. The aim of the present study was to evaluate the interoceptive conditioning account using 20% carbon dioxide (CO(2))-enriched air as an interoceptive conditioned stimulus (CS) (i.e., physiologically inert 5-s exposures) and unconditioned stimulus (US) (i.e., physiologically prepotent 15-s exposures). Healthy participants (N=42) were randomly assigned to one of three conditions: a CS-only, contingent CS-US pairings, or unpaired/non-contingent CS and US presentations. Electrodermal and self-report (e.g., distress, fear) served as indices of conditioned emotional responding. Results showed greater magnitude electrodermal and evaluative fear conditioning in the paired relative to the CS-only condition. The explicitly unpaired condition showed even greater electrodermal and evaluative responding during acquisition, and marked resistance to extinction. The latter results are consistent with the possibility that the unpaired procedure constituted a partial reinforcement procedure in which CO(2) onset was paired with more extended CO(2) exposure on 50% of the trials. Overall, the findings are consistent with contemporary learning theory accounts of panic.

  8. Extended necessary condition for local operations and classical communication: Tight bound for all measurements

    Science.gov (United States)

    Cohen, Scott M.

    2015-06-01

    We give a necessary condition that a separable measurement can be implemented by local quantum operations and classical communication (LOCC) in any finite number of rounds of communication, generalizing and strengthening a result obtained previously. That earlier result involved a bound that is tight when the number of measurement operators defining the measurement is relatively small. The present results generalize that bound to one that is tight for any finite number of measurement operators, and we also provide an extension which holds when that number is infinite. We apply these results to the famous example on a 3 ×3 system known as "domino states," which were the first demonstration of nonlocality without entanglement. Our extended necessary condition provides another way of showing that these states cannot be perfectly distinguished by (finite-round) LOCC. It directly shows that this conclusion also holds for their related rotated domino states. We also introduce a class of problems involving the unambiguous discrimination of quantum states, each of which is an example where the states can be optimally discriminated by a separable measurement, but according to our condition, cannot be optimally discriminated by LOCC. These examples nicely illustrate the usefulness of the present results, since our earlier necessary condition, which the present result generalizes, is not strong enough to reach a conclusion in any of these cases.

  9. The effects of ethanol on the developing cerebellum and eyeblink classical conditioning.

    Science.gov (United States)

    Green, John T

    2004-01-01

    In rats, developmental ethanol exposure has been used to model the central nervous system deficits associated with human fetal alcohol syndrome. Binge-like ethanol exposure of neonatal rats depletes cells in the cerebellum, including Purkinje cells, granule cells, and deep nuclear cells, and produces deficits in simple tests of motor coordination. However, the extent to which anatomical damage is related to behavioral deficits has been difficult to estimate. Eyeblink classical conditioning is known to engage a discrete brain stem-cerebellar circuit, making it an ideal test of cerebellar functional integrity after developmental ethanol exposure. Eyeblink conditioning is a simple form of motor learning in which a neutral stimulus (such as a tone) comes to elicit an eyeblink when repeatedly paired with a stimulus that evokes an eyeblink prior to training (such as mild periorbital stimulation). In eyeblink conditioning, one of the deep cerebellar nuclei, the interpositus nucleus, as well as specific Purkinje cell populations, are sites of convergence for tone conditioned stimulus and somatosensory unconditioned stimulus information, and, together with brain stem nuclei, provide the necessary and sufficient substrate for the learned response. A series of studies have shown that eyeblink conditioning is impaired in both weanling and adult rats given binge-like exposure to ethanol as neonates. In addition, interpositus nucleus neurons from ethanol-exposed rats showed impaired activation during eyeblink conditioning. These deficits are accompanied by a permanent reduction In the deep cerebellar nuclear cell population. Because particular cerebellar cell populations are utilized in well-defined ways during eyeblink conditioning, conclusions regarding the underlying neural substrates of behavioral change after developmental ethanol exposure are greatly strengthened.

  10. Spectral boundary conditions and solitonic solutions in a classical Sellmeier dielectric

    CERN Document Server

    Belgiorno, F; Viganò, A

    2016-01-01

    Electromagnetic field interactions in a dielectric medium represent a longstanding field of investigation, both at the classical level and at the quantum one. We propose a 1+1 dimensional toy-model which consists of an half-line filling dielectric medium, with the aim to set up a simplified situation where technicalities related to gauge invariance and, as a consequence, physics of constrained systems are avoided, and still interesting features appear. In particular, we simulate the electromagnetic field and the polarization field by means of two coupled scalar fields $\\phi$,$\\psi$ respectively, in a Hopfield-like model. We find that, in order to obtain a physically meaningful behaviour for the model, one has to introduce spectral boundary conditions depending on the particle spectrum one is dealing with. This is the first interesting achievement of our analysis. The second relevant achievement is that, by introducing a nonlinear contribution in the polarization field $\\psi$, with the aim of mimicking a third...

  11. 4- to 6-week-old adult-born hippocampal neurons influence novelty-evoked exploration and contextual fear conditioning.

    Science.gov (United States)

    Denny, Christine A; Burghardt, Nesha S; Schachter, Daniel M; Hen, René; Drew, Michael R

    2012-05-01

    To explore the role of adult hippocampal neurogenesis in novelty processing, we assessed novel object recognition (NOR) in mice after neurogenesis was arrested using focal x-irradiation of the hippocampus, or a reversible, genetic method in which glial fibrillary acidic protein-positive neural progenitor cells are ablated with ganciclovir. Arresting neurogenesis did not alter general activity or object investigation during four exposures with two constant objects. However, when a novel object replaced a constant object, mice with neurogenesis arrested by either ablation method showed increased exploration of the novel object when compared with control mice. The increased novel object exploration did not manifest until 4-6 weeks after x-irradiation or 6 weeks following a genetic ablation, indicating that exploration of the novel object is increased specifically by the elimination of 4- to 6-week-old adult born neurons. The increased novel object exploration was also observed in older mice, which exhibited a marked reduction in neurogenesis relative to young mice. Mice with neurogenesis arrested by either ablation method were also impaired in one-trial contextual fear conditioning (CFC) at 6 weeks but not at 4 weeks following ablation, further supporting the idea that 4- to 6-week-old adult born neurons are necessary for specific forms of hippocampal-dependent learning, and suggesting that the NOR and CFC effects have a common underlying mechanism. These data suggest that the transient enhancement of plasticity observed in young adult-born neurons contributes to cognitive functions.

  12. L -sulpiride, at antidepressant dosage, prevents conditioned-fear stress-induced gastric lesions in rats.

    Science.gov (United States)

    Benelli, A; De Pol A; Poggioli, R; Cavazzuti, E; Arletti, R; Bertolini, A; Vergoni, A V

    2000-08-01

    It has been previously shown that long-term treatment with low doses of l-sulpiride is highly effective in rat models of depression and of anticipatory anxiety/panic behavior. The present study was aimed at investigating whether the same treatment can prevent the ulcerogenic effect of repeated inescapable stresses. In adult rats, the repeated (7 consecutive days) exposure to an uncontrollable stressful condition (inescapable 2.5 mA scrambled shock for 60 s) produced the development of gastric lesions (multiple punctiform telangiectasias in all rats, with superficial erosions or more severe ulcerations in 10 out 13 rats; score 4.67 +/- 0.44). l-sulpiride, intraperitoneally injected once a day at an antidepressant dose level (4 mg kg(-1) per day), starting 21 days before the beginning of the 7-day sequence of inescapable punishments ( = 28 daily treatments), almost completely prevented the stress-induced gastric injury (score 1.67 +/- 0.29; Psulpiride prevents the development of gastric lesions induced by chronic exposure to uncontrollable stress.

  13. Bilateral plasticity of Vibrissae SII representation induced by classical conditioning in mice.

    Science.gov (United States)

    Debowska, Weronika; Liguz-Lecznar, Monika; Kossut, Malgorzata

    2011-04-01

    The somatosensory cortex in mice contains primary (SI) and secondary (SII) areas, differing in somatotopic precision, topographic organization, and function. The role of SII in somatosensory processing is still poorly understood. SII is activated bilaterally during attentional tasks and is considered to play a role in tactile memory and sensorimotor integration. We measured the plasticity of SII activation after associative learning based on classical conditioning, in which unilateral stimulation of one row of vibrissae was paired with a tail shock. The training consisted of three daily 10 min sessions, during which 40 pairings were delivered. Cortical activation driven by stimulation of vibrissae was mapped with 2-[(14)C]deoxyglucose (2DG) autoradiography 1 d after the end of conditioning. We reported previously that the conditioning procedure resulted in unilateral enlargement of 2DG-labeled cortical representation of the "trained" row of vibrissae in SI. Here, we measured the width and intensity of the labeled region in SII. We found that both measured parameters in SII increased bilaterally. The increase was observed in cortical layers II/III and IV. Apparently, plasticity in SII is not a simple reflection of changes in SI. It may be attributable to bilateral integrative role of SII, its lesser topographical specificity, and strong involvement in attentional processing.

  14. Reversible inactivation of the entorhinal cortex disrupts the establishment and expression of latent inhibition of cued fear conditioning in C57BL/6 mice.

    Science.gov (United States)

    Lewis, Michael C; Gould, Thomas J

    2007-01-01

    For latent inhibition, preexposure to a conditioned stimulus (CS) prior to training with an unconditioned stimulus (US) results in decreased conditioned responses (CRs) to the CS at the time of testing. The mechanism by which decreased CRs occurs, however, is unknown; CS preexposure may interfere with subsequent conditioning, or modulate the expression of CRs. Previous research has suggested that the entorhinal cortex (EC) is necessary for latent inhibition of a variety of tasks. However, no studies have specifically compared the role of the EC in acquisition vs. expression of latent inhibition. The present study used reversible inactivation of the EC to address this issue. The GABA agonist muscimol (0.5 microg/side) was directly infused into the EC of mice prior to CS preexposure, training, or testing. Our results indicate that muscimol inactivation of the EC before CS preexposure disrupts latent inhibition of cued fear conditioning. Importantly, this same dose of muscimol did not disrupt cued fear conditioning, nor did it affect latent inhibition when infused into the subiculum. Furthermore, inactivation of the EC at testing disrupted the expression of latent inhibition of cued fear conditioning; that is, CS preexposed mice that received entorhinal cortical muscimol infusion at testing showed CRs compared to saline-infused CS preexposed mice. These findings suggest that repeated preexposure to the CS during latent inhibition may alter entorhinal cortical activity thereby allowing the EC to exert inhibitory control over the expression of CRs during testing of CS preexposed mice.

  15. Project DyAdd: classical eyeblink conditioning in adults with dyslexia and ADHD.

    Science.gov (United States)

    Laasonen, Marja; Kauppinen, Jenni; Leppämäki, Sami; Tani, Pekka; Harno, Hanna; Hokkanen, Laura; Wikgren, Jan

    2012-11-01

    In this study of the project DyAdd (Adult Dyslexia and Attention Deficit Disorder in Finland), classical eyeblink conditioning (EBC) was investigated in both delay and trace paradigms in adults (18-55 years) with dyslexia (n = 37), attention deficit-hyperactivity disorder (ADHD; n = 21), their comorbid combination (n = 8), and healthy controls (n = 35). In addition, the profiles of three participants with a rare autosomal dominant cerebellar disease were assessed (episodic ataxia type 2, EA-2). We found that participants with dyslexia were overall slower learners than controls in eyeblink conditioning. Further, they were the only group that had a reduced number of CRs in mediotemporal-dependent trace paradigm compared to the more cerebellum-dependent delay paradigm. Second, ADHD was found to be related to larger CR amplitude. Third, those with a comorbid condition learned faster and manifested CRs that were not well timed. Fourth, the cerebellar patients showed nearly no conditioning at all. Correlations between EBC and various neuropsychological domains (phonological processing, reading, spelling, arithmetic, executive functions, attention, and fine motor control) over all participants resulted in significant relations only for the delay paradigm: Increased amount of reading errors related with later peak latency and increased amount of self-corrections in fine motor control related with larger response magnitude. Within those who conditioned, relations emerged only for the trace paradigm: better spelling was related to larger response magnitude. These results do not lend support to the cerebellar hypothesis of dyslexia. On the contrary, dyslexia in its pure form seems to be related to a relative dysfunction of a larger hippocampal-cerebellar network. Further, larger responses in the ADHD group are suggested to result from their lowered responding threshold.

  16. Transfer of classical eyeblink conditioning with electrical stimulation of mPFC or tone as conditioned stimulus in guinea pigs.

    Science.gov (United States)

    Yao, Juan; Wu, Guang-Yan; Liu, Guo-Long; Liu, Shu-Lei; Yang, Yi; Wu, Bing; Li, Xuan; Feng, Hua; Sui, Jian-Feng

    2014-11-01

    Learning with a stimulus from one sensory modality can facilitate subsequent learning with a new stimulus from a different sensory modality. To date, the characteristics and mechanism of this phenomenon named transfer effect still remain ambiguous. Our previous work showed that electrical stimulation of medial prefrontal cortex (mPFC) as a conditioned stimulus (CS) could successfully establish classical eyeblink conditioning (EBC). The present study aimed to (1) observe whether transfer of EBC learning would occur when CSs shift between central (mPFC electrical stimulation as a CS, mPFC-CS) and peripheral (tone as a CS, tone CS); (2) compare the difference in transfer effect between the two paradigms, delay EBC (DEBC) and trace EBC (TEBC). A total of 8 groups of guinea pigs were tested in the study, including 4 experimental groups and 4 control groups. Firstly, the experimental groups accepted central (or peripheral) CS paired with corneal airpuff unconditioned stimulus (US); then, CS shifted to the peripheral (or central) and paired with US. The control groups accepted corresponding central (or peripheral) CS and pseudo-paired with US, and then shifted CS from central (or peripheral) to peripheral (or central) and paired with US. The results showed that the acquisition rates of EBC were higher in experimental groups than in control groups after CS switching from central to peripheral or vice versa, and the CR acquisition rate was remarkably higher in DEBC than in TEBC in both transfer ways. The results indicate that EBC transfer can occur between learning established with mPFC-CS and tone CS. Memory of CS-US association for delay paradigm was less disturbed by the sudden switch of CS than for trace paradigm. This study provides new insight into neural mechanisms underlying conditioned reflex as well as the role of mPFC.

  17. Intact neurogenesis is required for benefits of exercise on spatial memory but not motor performance or contextual fear conditioning in C57BL/6J mice.

    Science.gov (United States)

    Clark, P J; Brzezinska, W J; Thomas, M W; Ryzhenko, N A; Toshkov, S A; Rhodes, J S

    2008-09-09

    The mammalian hippocampus continues to generate new neurons throughout life. Experiences such as exercise, anti-depressants, and stress regulate levels of neurogenesis. Exercise increases adult hippocampal neurogenesis and enhances behavioral performance on rotarod, contextual fear and water maze in rodents. To directly test whether intact neurogenesis is required for gains in behavioral performance from exercise in C57BL/6J mice, neurogenesis was reduced using focal gamma irradiation (3 sessions of 5 Gy). Two months after treatment, mice (total n=42 males and 42 females) (Irradiated or Sham), were placed with or without running wheels (Runner or Sedentary) for 54 days. The first 10 days mice received daily injections of bromodeoxyuridine (BrdU) to label dividing cells. The last 14 days mice were tested on water maze (two trials per day for 5 days, then 1 h later probe test), rotarod (four trials per day for 3 days), and contextual fear conditioning (2 days), then measured for neurogenesis using immunohistochemical detection of BrdU and neuronal nuclear protein (NeuN) mature neuronal marker. Consistent with previous studies, in Sham animals, running increased neurogenesis fourfold and gains in performance were observed for the water maze (spatial learning and memory), rotarod (motor performance), and contextual fear (conditioning). These positive results provided the reference to determine whether gains in performance were blocked by irradiation. Irradiation reduced neurogenesis by 50% in both groups, Runner and Sedentary. Irradiation did not affect running or baseline performance on any task. Minimal changes in microglia associated with inflammation (using immunohistochemical detection of cd68) were detected at the time of behavioral testing. Irradiation did not reduce gains in performance on rotarod or contextual fear, however it eliminated gain in performance on the water maze. Results support the hypothesis that intact exercise-induced hippocampal neurogenesis

  18. Autonomic control of heart rate and blood pressure in spontaneously hypertensive rats during aversive classical conditioning.

    Science.gov (United States)

    Hatton, D C; Buchholz, R A; Fitzgerald, R D

    1981-12-01

    An examination was made of the heart rate (HR) and blood pressure (BP) responses of 7-9-wk-old spontaneously hypertensive rats (SHR) and genetical control Wistar/Kyoto (WKY) rats during aversive classical conditioning. Subsequent to the development of conditioned responding (CRs), assessments were made of the effects of selective autonomic blockade by methyl atropine (10 mg/kg), phentolamine (2 mg/kg), and propranolol (2 mg/kg). The CR complex in the two strains consisted of pressor BP CRs in conjunction with vagally mediated decelerative HR CRs in the SHR strain and sympathetically mediated accelerative HR CRs in the WKY strain. The decelerative SHR HR CR did not appear to be secondary to baroreceptor reflex activity, although such activity did appear to be involved in the pressor BP and decelerative HR orienting response (OR) and unconditioned response (UR) complex of the SHRs on the initial application of the CS and the US, respectively. Augmented pressor BP ORs, CRs, and URs in the SHRs relative to the WKYs and differential drug effects on BP and HR baselines of the two strains suggested the presence of enhanced sympathetic activity in the SHRs that was not reflected in the SHR decelerative HR CR. Phentolamine unmasked evidence of reflex beta 2-vasodilation deficiency in the SHRs that could have contributed to the enhancement of their BP OR and CR.

  19. Hippocampal Processing of Ambiguity Enhances Fear Memory.

    Science.gov (United States)

    Amadi, Ugwechi; Lim, Seh Hong; Liu, Elizabeth; Baratta, Michael V; Goosens, Ki A

    2017-02-01

    Despite the ubiquitous use of Pavlovian fear conditioning as a model for fear learning, the highly predictable conditions used in the laboratory do not resemble real-world conditions, in which dangerous situations can lead to unpleasant outcomes in unpredictable ways. In the current experiments, we varied the timing of aversive events after predictive cues in rodents and discovered that temporal ambiguity of aversive events greatly enhances fear. During fear conditioning with unpredictably timed aversive events, pharmacological inactivation of the dorsal hippocampus or optogenetic silencing of cornu ammonis 1 cells during aversive negative prediction errors prevented this enhancement of fear without affecting fear learning for predictable events. Dorsal hippocampal inactivation also prevented ambiguity-related enhancement of fear during auditory fear conditioning under a partial-reinforcement schedule. These results reveal that information about the timing and occurrence of aversive events is rapidly acquired and that unexpectedly timed or omitted aversive events generate hippocampal signals to enhance fear learning.

  20. Classical conditioning for preserving the effects of short melatonin treatment in children with delayed sleep: a pilot study

    Science.gov (United States)

    van Maanen, Annette; Meijer, Anne Marie; Smits, Marcel G; Oort, Frans J

    2017-01-01

    Melatonin treatment is effective in treating sleep onset problems in children with delayed melatonin onset, but effects usually disappear when treatment is discontinued. In this pilot study, we investigated whether classical conditioning might help in preserving treatment effects of melatonin in children with sleep onset problems, with and without comorbid attention deficit hyperactivity disorder (ADHD) or autism. After a baseline week, 16 children (mean age: 9.92 years, 31% ADHD/autism) received melatonin treatment for 3 weeks and then gradually discontinued the treatment. Classical conditioning was applied by having children drink organic lemonade while taking melatonin and by using a dim red light lamp that was turned on when children went to bed. Results were compared with a group of 41 children (mean age: 9.43 years, 34% ADHD/autism) who received melatonin without classical conditioning. Melatonin treatment was effective in advancing dim light melatonin onset and reducing sleep onset problems, and positive effects were found on health and behavior problems. After stopping melatonin, sleep returned to baseline levels. We found that for children without comorbidity in the experimental group, sleep latency and sleep start delayed less in the stop week, which suggests an effect of classical conditioning. However, classical conditioning seems counterproductive in children with ADHD or autism. Further research is needed to establish these results and to examine other ways to preserve melatonin treatment effects, for example, by applying morning light.

  1. Reinforcement in an in Vitro Analog of Appetitive Classical Conditioning of Feeding Behavior in "Aplysia": Blockade by a Dopamine Antagonist

    Science.gov (United States)

    Reyes, Fredy D.; Mozzachiodi, Riccardo; Baxter, Douglas A.; Byrne, John H.

    2005-01-01

    In a recently developed in vitro analog of appetitive classical conditioning of feeding in "Aplysia," the unconditioned stimulus (US) was electrical stimulation of the esophageal nerve (En). This nerve is rich in dopamine (DA)-containing processes, which suggests that DA mediates reinforcement during appetitive conditioning. To test this…

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

    Science.gov (United States)

    Kaplan, Gary B; Moore, Katherine A

    2011-08-01

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

  3. Investigating the Role of Hippocampal BDNF in Anxiety Vulnerability Using Classical Eyeblink Conditioning.

    Science.gov (United States)

    Janke, Kellie L; Cominski, Tara P; Kuzhikandathil, Eldo V; Servatius, Richard J; Pang, Kevin C H

    2015-01-01

    Dysregulation of brain-derived neurotrophic factor (BDNF), behavioral inhibition temperament (BI), and small hippocampal volume have been linked to anxiety disorders. Individuals with BI show facilitated acquisition of the classically conditioned eyeblink response (CCER) as compared to non-BI individuals, and a similar pattern is seen in an animal model of BI, the Wistar-Kyoto (WKY) rat. The present study examined the role of hippocampal BDNF in the facilitated delay CCER of WKY rats. Consistent with earlier work, acquisition was facilitated in WKY rats compared to the Sprague Dawley (SD) rats. Facilitated acquisition was associated with increased BDNF, TrkB, and Arc mRNA in the dentate gyrus of SD rats, but learning-induced increases in BDNF and Arc mRNA were significantly smaller in WKY rats. To determine whether reduced hippocampal BDNF in WKY rats was a contributing factor for their facilitated CCER, BDNF or saline infusions were given bilaterally into the dentate gyrus region 1 h prior to training. BDNF infusion did not alter the acquisition of SD rats, but significantly dampened the acquisition of CCER in the WKY rats, such that acquisition was similar to SD rats. Together, these results suggest that inherent differences in the BDNF system play a critical role in the facilitated associative learning exhibited by WKY rats, and potentially individuals with BI. Facilitated associative learning may represent a vulnerability factor in the development of anxiety disorders.

  4. Investigating the role of hippocampal BDNF in anxiety vulnerability using classical eyeblink conditioning

    Directory of Open Access Journals (Sweden)

    Kellie L Janke

    2015-07-01

    Full Text Available Dysregulation of brain-derived neurotrophic factor (BDNF, behavioral inhibition temperament (BI and small hippocampal volume have been linked to anxiety disorders. Individuals with BI show facilitated acquisition of the classically conditioned eyeblink response (CCER as compared to non-BI individuals, and a similar pattern is seen in an animal model of BI, the Wistar-Kyoto (WKY rat. The present study examined the role of hippocampal BDNF in the facilitated delay CCER of WKY rats. Consistent with earlier work, acquisition was facilitated in WKY rats compared to the SD rats. Facilitated acquisition was associated with increased BDNF, TrkB, and Arc mRNA in the dentate gyrus of SD rats, but learning-induced increases in BDNF and Arc mRNA were significantly smaller in WKY rats. To determine if reduced hippocampal BDNF in WKY rats was a contributing factor for their facilitated CCER, BDNF or saline infusions were given bilaterally into the dentate gyrus region one hour prior to training. BDNF infusion did not alter the acquisition of SD rats, but significantly dampened the acquisition of CCER in the WKY rats, such that acquisition was similar to SD rats. Together, these results suggest that inherent differences in the BDNF system play a critical role in the facilitated associative learning exhibited by WKY rats, and potentially individuals with BI. Facilitated associative learning may represent a vulnerability factor in the development of anxiety disorders.

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

    Science.gov (United States)

    Dong, Xinwen; Li, Yonghui; Kirouac, Gilbert J

    2015-01-01

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

  6. Modelling the fear effect in predator-prey interactions.

    Science.gov (United States)

    Wang, Xiaoying; Zanette, Liana; Zou, Xingfu

    2016-11-01

    A recent field manipulation on a terrestrial vertebrate showed that the fear of predators alone altered anti-predator defences to such an extent that it greatly reduced the reproduction of prey. Because fear can evidently affect the populations of terrestrial vertebrates, we proposed a predator-prey model incorporating the cost of fear into prey reproduction. Our mathematical analyses show that high levels of fear (or equivalently strong anti-predator responses) can stabilize the predator-prey system by excluding the existence of periodic solutions. However, relatively low levels of fear can induce multiple limit cycles via subcritical Hopf bifurcations, leading to a bi-stability phenomenon. Compared to classic predator-prey models which ignore the cost of fear where Hopf bifurcations are typically supercritical, Hopf bifurcations in our model can be both supercritical and subcritical by choosing different sets of parameters. We conducted numerical simulations to explore the relationships between fear effects and other biologically related parameters (e.g. birth/death rate of adult prey), which further demonstrate the impact that fear can have in predator-prey interactions. For example, we found that under the conditions of a Hopf bifurcation, an increase in the level of fear may alter the direction of Hopf bifurcation from supercritical to subcritical when the birth rate of prey increases accordingly. Our simulations also show that the prey is less sensitive in perceiving predation risk with increasing birth rate of prey or increasing death rate of predators, but demonstrate that animals will mount stronger anti-predator defences as the attack rate of predators increases.

  7. Fear extinction, persistent disruptive behavior and psychopathic traits: fMRI in late adolescence.

    Science.gov (United States)

    Cohn, Moran D; van Lith, Koen; Kindt, Merel; Pape, Louise E; Doreleijers, Theo A H; van den Brink, Wim; Veltman, Dick J; Popma, Arne

    2016-07-01

    Children diagnosed with a Disruptive Behavior Disorder (DBD, i.e. Oppositional Defiant Disorder or Conduct Disorder), especially those with psychopathic traits, are at risk of developing persistent and severe antisocial behavior. Reduced fear conditioning has been proposed to underlie persistent antisocial development. However, we have recently shown that both DBD persisters and desisters are characterized by increased fear conditioning compared with healthy controls (HCs). In this study, we investigated whether brain function during fear extinction is associated with DBD subgroup-membership and psychopathic traits. Adolescents from a childhood arrestee cohort (mean age 17.6 years, s.d. 1.4) who met criteria for a DBD diagnosis during previous assessments were re-assessed and categorized as persistent DBD (n = 25) or desistent DBD (n = 25). Functional MRI during the extinction phase of a classical fear-conditioning task was used to compare regional brain function between these subgroups and 25 matched controls. Both DBD persisters and desisters showed hyperreactivity during fear extinction, when compared with HCs. Impulsive-irresponsible psychopathic traits were positively associated with responses in the fear neurocircuitry and mediated the association between neural activation and group membership. These results suggest that fear acquisition and fear extinction deficits may provide an endophenotype for an emotionally hyperreactive subtype of antisocial development.

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

    Directory of Open Access Journals (Sweden)

    B. Kayisoglu

    2006-01-01

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

  9. Stress-induced enhancement of fear conditioning activates the amygdalar cholecystokinin system in a rat model of post-traumatic stress disorder.

    Science.gov (United States)

    Feng, Ting; Yang, Shengchang; Wen, Di; Sun, Qiming; Li, Yingmin; Ma, Chunling; Cong, Bin

    2014-10-01

    Post-traumatic stress disorder (PTSD), a debilitating psychiatric disease characterized by invasive and persistent fear memories-induced stressful experience, is associated with numerous changes in neuroendocrine function. Here, we investigated whether PTSD-like symptoms are associated with changes in the cholecystokinin (CCK) system in the basolateral amygdala. We developed an animal model of PTSD using multiple foot shocks at 1.1 mA. The resulting conditioned fear response was severe (>80% freezing) and maintained for at least 28 days. The stress-associated neurotransmitters norepinephrine, dopamine, and corticotrophin-releasing hormone were elevated at 1 day after foot shock. CCK immunoreactivity and extracellular concentration as well as the expression of CCK receptors (CCK1R, CCK2R) increased progressively for 28 days following foot shock. Taken together, these results suggest that stress-induced activation of the CCK system in the BLA, which may contribute toward the development of PTSD-like symptoms.

  10. Reinforcement in an in vitro analog of appetitive classical conditioning of feeding behavior in Aplysia: blockade by a dopamine antagonist.

    Science.gov (United States)

    Reyes, Fredy D; Mozzachiodi, Riccardo; Baxter, Douglas A; Byrne, John H

    2005-01-01

    In a recently developed in vitro analog of appetitive classical conditioning of feeding in Aplysia, the unconditioned stimulus (US) was electrical stimulation of the esophageal nerve (En). This nerve is rich in dopamine (DA)-containing processes, which suggests that DA mediates reinforcement during appetitive conditioning. To test this possibility, methylergonovine was used to antagonize DA receptors. Methylergonovine (1 nM) blocked the pairing-specific increase in fictive feeding that is usually induced by in vitro classical conditioning. The present results and previous observation that methylergonovine also blocks the effects of contingent reinforcement in an in vitro analog of appetitive operant conditioning suggest that DA mediates reinforcement for appetitive associative conditioning of feeding in Aplysia.

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

    Science.gov (United States)

    Cicchese, Joseph J; Berry, Stephen D

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Janik Vincent M

    2011-04-01

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

  13. Acquisition of Pavlovian fear conditioning using β-adrenoceptor activation of the dorsal premammillary nucleus as an unconditioned stimulus to mimic live predator-threat exposure.

    Science.gov (United States)

    Pavesi, Eloisa; Canteras, Newton S; Carobrez, Antônio P

    2011-04-01

    In the present work, we sought to mimic the internal state changes in response to a predator threat by pharmacologically stimulating the brain circuit involved in mediating predator fear responses, and explored whether this stimulation would be a valuable unconditioned stimulus (US) in an olfactory fear conditioning paradigm (OFC). The dorsal premammillary nucleus (PMd) is a key brain structure in the neural processing of anti-predatory defensive behavior and has also been shown to mediate the acquisition and expression of anti-predatory contextual conditioning fear responses. Rats were conditioned by pairing the US, which was an intra-PMd microinjection of isoproterenol (ISO; β-adrenoceptor agonist), with amyl acetate odor-the conditioned stimulus (CS). ISO (10 and 40 nmol) induced the acquisition of the OFC and the second-order association by activation of β-1 receptors in the PMd. Furthermore, similar to what had been found for contextual conditioning to a predator threat, atenolol (β-1 receptor antagonist) in the PMd also impaired the acquisition and expression of OFC promoted by ISO. Considering the strong glutamatergic projections from the PMd to the dorsal periaqueductal gray (dPAG), we tested how the glutamatergic blockade of the dPAG would interfere with the OFC induced by ISO. Accordingly, microinjections of NMDA receptor antagonist (AP5, 6 nmol) into the dPAG were able to block both the acquisition, and partially, the expression of the OFC. In conclusion, we have found that PMd β-1 adrenergic stimulation is a good model to mimic predatory threat-induced internal state changes, and works as a US able to mobilize the same systems involved in the acquisition and expression of predator-related contextual conditioning.

  14. Neonatal isolation decreases cued fear conditioning and frontal cortical histone 3 lysine 9 methylation in adult female rats.

    Science.gov (United States)

    Kao, Gour-Shenq; Cheng, Ling-Yi; Chen, Li-Hsien; Tzeng, Wen-Yu; Cherng, Chienfang G; Su, Chien-Chou; Wang, Ching-Yi; Yu, Lung

    2012-12-15

    Early life stress is thought to enhance adult susceptibility to stress and stress-related mood disorders. In this study, fear-potentiated startle was used to model the acquisition of a traumatic event-related memory in female rats experiencing early life stress. Daily 1-hr maternal and sibling separation throughout day 2-9 postpartum (D2-9 PP) caused a decrease in the fear-potentiated startle, but not acoustic startle baseline, in adult female rats. The separation procedure did not affect corticosterone secretion but produced an increase in serum estradiol concentration. Moreover, the separation procedure did not affect histone 3 lysine 9 (H3K9) acetylation but decreased H3K9 mono- and tri-methylation in frontal cortices. Treatment with 5-aza-2'-deoxycytidine (AZA) (5mg/kg at alternative days from D2PP to D9PP or 10mg/kg at D5PP and D9PP), a DNA methylation inhibitor, did not affect the separation-decreased fear-potentiated startle. Treatment with valproic acid (VPA), a histone deacetylase inhibitor, at 3 dosing regimens (300mg/kg at D2-9PP; 100mg/kg at D2-4PP, 200mg/kg at D5-7PP, 300mg/kg at D8-9PP; 100mg/kg at D2-5PP, 200mg/kg at D6-9PP) prior to daily separation reversed such a decrease in fear-potentiated startle. The lowest effective VPA dosing regimen used (100mg/kg at D2-5PP, 200mg/kg at D6-9PP) reversed the separation-decreased H3K9 mono- and tri-methylation in frontal cortices. Eight-day VPA (300mg/kg/day) and AZA (5mg/kg/day) administrations starting at D28PP were ineffective in altering the separation-decreased fear-potentiated startle. We, hereby, suggest that decreased frontal cortical H3K9 mono- and tri-methylation may be involved in early life separation-decreased fear memory of adult rats.

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

    Science.gov (United States)

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

    2007-01-01

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

  16. Increased levels of conditioned fear and avoidance behavior coincide with changes in phosphorylation of the protein kinase B (AKT) within the amygdala in a mouse model of extremes in trait anxiety.

    Science.gov (United States)

    Yen, Yi-Chun; Mauch, Christoph P; Dahlhoff, Maik; Micale, Vincenzo; Bunck, Mirjam; Sartori, Simone B; Singewald, Nicolas; Landgraf, Rainer; Wotjak, Carsten T

    2012-07-01

    Patients diagnosed for anxiety disorders often display faster acquisition and slower extinction of learned fear. To gain further insights into the mechanisms underlying these phenomenona, we studied conditioned fear in mice originating form a bi-directional selective breeding approach, which is based on elevated plus-maze behavior and results in CD1-derived high (HAB), normal (NAB), and low (LAB) anxiety-related behavior mice. HAB mice displayed pronounced cued-conditioned fear compared to NAB/CD1 and LAB mice that coincided with increased phosphorylation of the protein kinase B (AKT) in the basolateral amygdala 45 min after conditioning. No similar changes were observed after non-associative immediate shock presentations. Fear extinction of recent but not older fear memories was preserved. However, HAB mice were more prone to relapse of conditioned fear with the passage of time. HAB mice also displayed higher levels of contextual fear compared to NAB and LAB mice and exaggerated avoidance following step-down avoidance training. Interestingly, HAB mice showed lower and LAB mice higher levels of acoustic startle responses compared to NAB controls. The increase in arousal observed in LAB mice coincided with the general absence of conditioned freezing. Taken together, our results suggest that the genetic predisposition to high anxiety-related behavior may increase the risk of forming traumatic memories, phobic-like fear and avoidance behavior following aversive encounters, with a clear bias towards passive coping styles. In contrast, genetic predisposition to low anxiety-related and high risk-taking behavior seems to be associated with an increase in active coping styles. Our data imply changes in AKT phosphorylation as a therapeutic target for the prevention of exaggerated fear memories.

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

    Institute of Scientific and Technical Information of China (English)

    黄任之; 李则宣; 陈欢; 黄月胜; 丁立平

    2012-01-01

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

  18. Nicotine Withdrawal-Induced Deficits in Trace Fear Conditioning in C57BL/6 Mice: A Role for High-Affinity β2 Subunit-Containing Nicotinic Acetylcholine Receptors

    OpenAIRE

    Raybuck, J. D.; Gould, T. J.

    2009-01-01

    Nicotine alters cognitive processes that include working memory and long-term memory. Trace fear conditioning may involve working memory during acquisition while also allowing the assessment of long-term memory. The present study used trace fear conditioning in C57BL/6 mice to investigate the effects of acute nicotine, chronic nicotine, and withdrawal of chronic nicotine on processes active during acquisition and recall 24 hours later and examine the nicotinic acetylcholine receptor subtypes ...

  19. Nicotine withdrawal disrupts both foreground and background contextual fear conditioning but not pre-pulse inhibition of the acoustic startle response in C57BL/6 mice.

    Science.gov (United States)

    André, Jessica M; Gulick, Danielle; Portugal, George S; Gould, Thomas J

    2008-07-19

    Nicotine withdrawal is associated with multiple symptoms such as anxiety, increased appetite, and disrupted cognition in humans. Although animal models have provided insights into the somatic and affective symptoms of nicotine withdrawal, less research has focused on the effects of nicotine withdrawal on cognition. Therefore, in this study, C57BL/6J mice were used to test the effects of withdrawal from chronic nicotine on foreground and background contextual fear conditioning, which present the context as a primary or secondary stimulus, respectively. Mice withdrawn from 12 days of chronic nicotine (6.3mg/kg/day) or saline were trained and tested in either foreground or background contextual fear conditioning; nicotine withdrawal-associated deficits in contextual fear conditioning were observed in both conditions. Mice were also tested for the effects of withdrawal on pre-pulse inhibition of the acoustic startle reflex (PPI), a measure of sensory gating, and on the acoustic startle reflex. Mice withdrawn from 12 days of chronic nicotine (6.3 or 12.6 mg/kg/day) or saline underwent one 30-min PPI and startle session; no effect of withdrawal from chronic nicotine on PPI or startle was observed for either dose at 24h after nicotine removal. Therefore, mice were tested at different time points following withdrawal from 12.6 mg/kg/day chronic nicotine (8, 24, and 48 h after nicotine removal). No effect of withdrawal from chronic nicotine was observed at any time point for PPI. Overall, these results demonstrate that nicotine withdrawal disrupts two methods of contextual learning but not sensory gating in C57BL/6J mice.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-07-01

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

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

    Institute of Scientific and Technical Information of China (English)

    孙楠; 魏艺铭; 李倩; 郑希付

    2012-01-01

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

  2. Consequences of ethanol exposure on cued and contextual fear conditioning and extinction differ depending on timing of exposure during adolescence or adulthood.

    Science.gov (United States)

    Broadwater, Margaret; Spear, Linda P

    2013-11-01

    Some evidence suggests that adolescents are more sensitive than adults to ethanol-induced cognitive deficits and that these effects may be long-lasting. The purpose of Exp 1 was to determine if early-mid adolescent [postnatal day (P) 28-48] intermittent ethanol exposure would affect later learning and memory in a Pavlovian fear conditioning paradigm differently than comparable exposures in adulthood (P70-90). In Exp 2 animals were exposed to ethanol during mid-late adolescence (P35-55) to assess whether age of initiation within the adolescent period would influence learning and memory differentially. Male Sprague-Dawley rats were given 4 g/kg i.g. ethanol (25%) or water every 48 h for a total of 11 exposures. After a 22 day non-ethanol period, animals were fear conditioned to a context (relatively hippocampal-dependent task) or tone (amygdala-dependent task), followed by retention tests and extinction (mPFC-dependent) of this conditioning. Despite similar acquisition, a deficit in context fear retention was evident in animals exposed to ethanol in early adolescence, an effect not observed after a comparable ethanol exposure in mid-late adolescence or adulthood. In contrast, animals that were exposed to ethanol in mid-late adolescence or adulthood showed enhanced resistance to context extinction. Together these findings suggest that repeated ethanol imparts long-lasting consequences on learning and memory, with outcomes that differ depending on age of exposure. These results may reflect differential influence of ethanol on the brain as it changes throughout ontogeny and may have implications for alcohol use not only throughout the developmental period of adolescence, but also in adulthood.

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

    Science.gov (United States)

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

    2004-01-01

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

  4. Temporal properties of fear extinction--does time matter?

    Science.gov (United States)

    Golkar, Armita; Bellander, Martin; Öhman, Arne

    2013-02-01

    Fear extinction can be defined as the weakening of the expression of a conditioned response (CR) by extended experience of nonreinforcement. Conceptually, two distinct models have been invoked to account for extinction. R. A. Rescorla and A. R. Wagner (1972, A theory of Pavlovian conditioning: Variations in the effectiveness of reinforcement and nonreinforcement, in A. H. B. W. F. Prokasy (Ed.), Classical conditioning: II. Current research and theory, pp. 64-99, New York, NY, Appleton-Century-Crofts) postulated that the number of exposure trials is the primary determinant of CR decrement, whereas C. R. Gallistel and J. Gibbon (2000, Time, rate, and conditioning, Psychological Review, Vol. 107, pp. 289-344) proposed that the decisive event is the cumulated exposure time to the nonreinforced conditioned stimulus (CS) elapsed after the last CS reinforcement. We evaluated these two accounts in a human differential fear conditioning study in which CR was measured with the fear-potentiated startle response. Cumulated duration of nonreinforcement fails to explain our findings, whereas the number of trials appeared critical. In fact, many CS trials with a duration shorter than the acquisition CS duration facilitated within-session extinction, but this effect did not predict the recovery of fear.

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

    Directory of Open Access Journals (Sweden)

    Nilsonne Gustav

    2011-11-01

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

  6. Synaptic plasticity and NO-cGMP-PKG signaling regulate pre- and postsynaptic alterations at rat lateral amygdala synapses following fear conditioning.

    Directory of Open Access Journals (Sweden)

    Kristie T Ota

    Full Text Available In vertebrate models of synaptic plasticity, signaling via the putative "retrograde messenger" nitric oxide (NO has been hypothesized to serve as a critical link between functional and structural alterations at pre- and postsynaptic sites. In the present study, we show that auditory Pavlovian fear conditioning is associated with significant and long-lasting increases in the expression of the postsynaptically-localized protein GluR1 and the presynaptically-localized proteins synaptophysin and synapsin in the lateral amygdala (LA within 24 hrs following training. Further, we show that rats given intra-LA infusion of either the NR2B-selective antagonist Ifenprodil, the NOS inhibitor 7-Ni, or the PKG inhibitor Rp-8-Br-PET-cGMPS exhibit significant decreases in training-induced expression of GluR1, synaptophysin, and synapsin immunoreactivity in the LA, while those rats infused with the PKG activator 8-Br-cGMP exhibit a significant increase in these proteins in the LA. In contrast, rats given intra-LA infusion of the NO scavenger c-PTIO exhibit a significant decrease in synapsin and synaptophysin expression in the LA, but no significant impairment in the expression of GluR1. Finally, we show that intra-LA infusions of the ROCK inhibitor Y-27632 or the CaMKII inhibitor KN-93 impair training-induced expression of GluR1, synapsin, and synaptophysin in the LA. These findings suggest that the NO-cGMP-PKG, Rho/ROCK, and CaMKII signaling pathways regulate fear memory consolidation, in part, by promoting both pre- and post-synaptic alterations at LA synapses. They further suggest that synaptic plasticity in the LA during auditory fear conditioning promotes alterations at presynaptic sites via NO-driven "retrograde signaling".

  7. Extracellular citrulline levels in the nucleus accumbens during the acquisition and extinction of a classical conditioned reflex with pain reinforcement.

    Science.gov (United States)

    Savel'ev, S A; Saul'skaya, N B

    2007-03-01

    Studies on Sprague-Dawley rats using in vivo microdialysis and HPLC showed that the acquisition and performance of a classical conditioned reflex with pain reinforcement was accompanied by increases in the concentrations of citrulline (a side product of nitric oxide formation) and arginine (the substrate of NO synthase) in the intercellular space of the nucleus accumbens. During extinction of the reflex, there was a decrease in the elevation of extracellular citrulline in this brain structure, which correlated with the extent of extinction of the reflex. Recovery of the reflex led to increases in arginine and citrulline levels in the nucleus accumbens. These data suggest that there is an increase in nitric oxide production in the nucleus accumbens during the acquisition and performance of a classical conditioned reflex with pain reinforcement, which decreases as the reflex is extinguished and recovers with recovery of the reflex.

  8. Neuronal circuits of fear extinction.

    Science.gov (United States)

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

    2010-02-01

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

  9. Fear learning circuitry is biased toward generalization of fear associations in posttraumatic stress disorder

    OpenAIRE

    Morey, R.A.; Dunsmoor, J E; Haswell, C C; Brown, V M; Vora, A; Weiner, J.; Stjepanovic, D; Wagner, H R; ,; Brancu, Mira; Marx, Christine E.; Naylor, Jennifer C.; Van Voorhees, Elizabeth; Taber, Katherine H.; Beckham, Jean C.

    2015-01-01

    Fear conditioning is an established model for investigating posttraumatic stress disorder (PTSD). However, symptom triggers may vaguely resemble the initial traumatic event, differing on a variety of sensory and affective dimensions. We extended the fear-conditioning model to assess generalization of conditioned fear on fear processing neurocircuitry in PTSD. Military veterans (n=67) consisting of PTSD (n=32) and trauma-exposed comparison (n=35) groups underwent functional magnetic resonance ...

  10. Immunization against social fear learning.

    Science.gov (United States)

    Golkar, Armita; Olsson, Andreas

    2016-06-01

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

  11. Fear at the Great Wall

    Institute of Scientific and Technical Information of China (English)

    CHARLOTTE SPIRES

    2011-01-01

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

  12. Fear at the Great Wall

    Institute of Scientific and Technical Information of China (English)

    CHARLOTTE; SPIRES

    2011-01-01

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

  13. Social Modulation of Associative Fear Learning by Pheromone Communication

    Science.gov (United States)

    Bredy, Timothy W.; Barad, Mark

    2009-01-01

    Mice communicate through visual, vocal, and olfactory cues that influence innate, nonassociative behavior. We here report that exposure to a recently fear-conditioned familiar mouse impairs acquisition of conditioned fear and facilitates fear extinction, effects mimicked by both an olfactory chemosignal emitted by a recently fear-conditioned…

  14. Classical and remote post-conditioning effects on ischemia/reperfusion-induced acute oxidant kidney injury.

    Science.gov (United States)

    Kadkhodaee, Mehri; Najafi, Atefeh; Seifi, Behjat

    2014-11-01

    The present study aimed to analyze and compare the effects of classical and remote ischemic postconditioning (POC) on rat renal ischemia/reperfusion (IR)-induced acute kidney injury. After right nephrectomy, male rats were randomly assigned into four groups (n = 8). In the IR group, 45 min of left renal artery occlusion was induced followed by 24 h of reperfusion. In the classical POC group, after induction of 45 min ischemia, 4 cycles of 10 s of intermittent ischemia and reperfusion were applied to the kidney before complete restoring of renal blood. In the remote POC group, 4 cycles of 5 min ischemia and reperfusion of left femoral artery were applied after 45 min renal ischemia and right at the time of renal reperfusion. There was a reduction in renal function (increase in blood urea and creatinine) in the IR group. Application of both forms of POC prevented the IR-induced reduction in renal function and histology. There were also significant improvements in kidney oxidative stress status in both POC groups demonstrated by a reduction in malondialdehyde (MDA) formation and preservation of antioxidant levels comparing to the IR group. We concluded that both methods of POC have protective effects on renal function and histology possibly by a reduction in IR-induced oxidative stress.

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

    Science.gov (United States)

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

    2016-06-01

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

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

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    N.S. Canteras

    2012-04-01

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

  17. Contrasts in Infant Classical Eyeblink Conditioning as a Function of Premature Birth

    Science.gov (United States)

    Herbert, Jane S.; Eckerman, Carol O.; Goldstein, Ricki F.; Stanton, Mark E.

    2004-01-01

    The impact of premature birth on associative learning was evaluated using simple delay eyeblink conditioning in which a tone conditional stimulus was paired with an air puff unconditional stimulus. Fourteen preterm (28-31 weeks gestation) and 11 full-term infants completed at least 3 conditioning sessions, 1 week apart, at 5 months of age…

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

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    Raffaele ed'Isa

    2011-12-01

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

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

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    Carina eMosig

    2014-10-01

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

  20. Expression of the immediate-early gene-encoded protein Egr-1 (zif268) during in vitro classical conditioning.

    Science.gov (United States)

    Mokin, Maxim; Keifer, Joyce

    2005-01-01

    Expression of the immediate-early genes (IEGs) has been shown to be induced by activity-dependent synaptic plasticity or behavioral training and is thought to play an important role in long-term memory. In the present study, we examined the induction and expression of the IEG-encoded protein Egr-1 during an in vitro neural correlate of eyeblink classical conditioning. The results showed that Egr-1 protein expression as determined by immunocytochemistry and Western blot analysis rapidly increased during the early stages of conditioning and remained elevated during the later stages. Further, expression of Egr-1 protein required NMDA receptor activation as it was blocked by bath application of AP-5. These findings suggest that the IEG-encoded proteins such as Egr-1 are activated during relatively simple forms of learning in vertebrates. In this case, Egr-1 may have a functional role in the acquisition phase of conditioning as well as in maintaining expression of conditioned responses.

  1. Do CS-US pairings actually matter? A within-subject comparison of instructed fear conditioning with and without actual CS-US pairings.

    Science.gov (United States)

    Raes, An K; De Houwer, Jan; De Schryver, Maarten; Brass, Marcel; Kalisch, Raffael

    2014-01-01

    Previous research showed that instructions about CS-US pairings can lead to fear of the CS even when the pairings are never presented. In the present study, we examined whether the experience of CS-US pairings adds to the effect of instructions by comparing instructed conditioning with and without actual CS-US pairings in a within-subject design. Thirty-two participants saw three fractals as CSs (CS(+)1, CS(+)2, CS(-)) and received electric shocks as USs. Before the start of a so-called training phase, participants were instructed that both CS(+)1 and CS(+)2 would be followed by the US, but only CS(+)1 was actually paired with the US. The absence of the US after CS(+)2 was explained in such a way that participants would not doubt the instructions about the CS(+)2-US relation. After the training phase, a test phase was carried out. In this phase, participants expected the US after both CS(+)s but none of the CS(+)s was actually paired with the US. During test, self-reported fear was initially higher for CS(+)1 than for CS(+)2, which indicates that the experience of actual CS-US pairings adds to instructions about these pairings. On the other hand, the CS(+)s elicited similar skin conductance responses and US expectancies. Theoretical and clinical implications are discussed.

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

    Institute of Scientific and Technical Information of China (English)

    李培培; 张丽丽; 韦美; 李敏

    2011-01-01

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

  3. Sensory prediction or motor control? Application of marr-albus type models of cerebellar function to classical conditioning.

    Science.gov (United States)

    Lepora, Nathan F; Porrill, John; Yeo, Christopher H; Dean, Paul

    2010-01-01

    Marr-Albus adaptive filter models of the cerebellum have been applied successfully to a range of sensory and motor control problems. Here we analyze their properties when applied to classical conditioning of the nictitating membrane response in rabbits. We consider a system-level model of eyeblink conditioning based on the anatomy of the eyeblink circuitry, comprising an adaptive filter model of the cerebellum, a comparator model of the inferior olive and a linear dynamic model of the nictitating membrane plant. To our knowledge, this is the first model that explicitly includes all these principal components, in particular the motor plant that is vital for shaping and timing the behavioral response. Model assumptions and parameters were systematically investigated to disambiguate basic computational capacities of the model from features requiring tuning of properties and parameter values. Without such tuning, the model robustly reproduced a range of behaviors related to sensory prediction, by displaying appropriate trial-level associative learning effects for both single and multiple stimuli, including blocking and conditioned inhibition. In contrast, successful reproduction of the real-time motor behavior depended on appropriate specification of the plant, cerebellum and comparator models. Although some of these properties appear consistent with the system biology, fundamental questions remain about how the biological parameters are chosen if the cerebellar microcircuit applies a common computation to many distinct behavioral tasks. It is possible that the response profiles in classical conditioning of the eyeblink depend upon operant contingencies that have previously prevailed, for example in naturally occurring avoidance movements.

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

    Science.gov (United States)

    Hunt, Pamela S; Barnet, Robert C

    2016-02-01

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

  5. Purkinje cell activity during classical conditioning with different conditional stimuli explains central tenet of Rescorla–Wagner model [corrected].

    Science.gov (United States)

    Rasmussen, Anders; Zucca, Riccardo; Johansson, Fredrik; Jirenhed, Dan-Anders; Hesslow, Germund

    2015-11-10

    A central tenet of Rescorla and Wagner's model of associative learning is that the reinforcement value of a paired trial diminishes as the associative strength between the presented stimuli increases. Despite its fundamental importance to behavioral sciences, the neural mechanisms underlying the model have not been fully explored. Here, we present findings that, taken together, can explain why a stronger association leads to a reduced reinforcement value, within the context of eyeblink conditioning. Specifically, we show that learned pause responses in Purkinje cells, which trigger adaptively timed conditioned eyeblinks, suppress the unconditional stimulus (US) signal in a graded manner. Furthermore, by examining how Purkinje cells respond to two distinct conditional stimuli and to a compound stimulus, we provide evidence that could potentially help explain the somewhat counterintuitive overexpectation phenomenon, which was derived from the Rescorla-Wagner model.

  6. Semantic classical conditioning and brain-computer interface (BCI control: Encoding of affirmative and negative thinking

    Directory of Open Access Journals (Sweden)

    Carolin A. Ruf

    2013-03-01

    Full Text Available The aim of the study was to investigate conditioned electroencephalographic (EEG responses to factually correct and incorrect statements in order to enable binary communication by means of a brain-computer interface (BCI. In two experiments with healthy participants true and false statements (serving as conditioned stimuli, CSs were paired with two different tones which served as unconditioned stimuli (USs. The features of the USs were varied and tested for their effectiveness to elicit differentiable conditioned reactions (CRs. After acquisition of the CRs, these CRs to true and false statements were classified offline using a radial basis function kernel support vector machine. A mean single-trial classification accuracy of 50.5% was achieved for differentiating conditioned yes versus no thinking and mean accuracies of 65.4% for classification of yes and 68.8% for no thinking (both relative to baseline were found using the best US. Analysis of the area under the curve of the conditioned EEG responses revealed significant differences between conditioned yes and no answers. Even though improvements are necessary, these first results indicate that the semantic conditioning paradigm could be a useful basis for further research regarding BCI communication in patients with complete locked-in syndrome (CLIS.

  7. The Classical Conditioning of Attitudes: A Comparative Study of Ages 8 to 18

    Science.gov (United States)

    O'Donnell, John M.; Brown, Mari J. K.

    1973-01-01

    Results of this study indicated that attitude conditioning increased with age and that the increase appeared to be a function of contingency awareness and perhaps also a function of the older subjects' having greater facility in transferring symbolic meaning. (Author)

  8. Can human autonomic classical conditioning occur without contingency awareness? The critical importance of the trial sequence.

    Science.gov (United States)

    Singh, Kulwinder; Dawson, Michael E; Schell, Anne M; Courtney, Christopher G; Payne, Andrew F H

    2013-04-01

    Most evidence suggests that awareness of the CS-US contingency is necessary for human autonomic conditioning. However, Schultz and Helmstetter (2010) reported unaware skin conductance conditioning using difficult-to-discriminate visual CSs. We sought to replicate these findings with procedures nearly identical to Schultz and Helmstetter among 66 participants. Results replicated the findings of significantly greater autonomic responding to CS+ than CS-; however, participants also demonstrated greater expectancy of shock to CS+ than CS- despite being classified as unaware. The differential expectancy and conditioning occurred only on trials that followed a CS+/CS- alternating sequence. On non-alternating trials, there was significantly higher expectancy and skin conductance responding to CS- compared to CS+. These results indicate that what initially appeared to be unaware differential conditioning was likely due to differential expectancy arising from a predictable trial sequence. These results underscore the critical importance of controlling for trial sequence effects in the study of learning.

  9. Phosphorylation of mitogen-activated protein kinase by one-trial and multi-trial classical conditioning.

    Science.gov (United States)

    Crow, T; Xue-Bian, J J; Siddiqi, V; Kang, Y; Neary, J T

    1998-05-01

    The pathway supporting the conditioned stimulus (CS) is one site of plasticity that has been studied extensively in conditioned Hermissenda. Several signal transduction pathways have been implicated in classical conditioning of this preparation, although the major emphasis has been on protein kinase C. Here we provide evidence for the activation and phosphorylation of a mitogen-activated protein kinase (MAPK) pathway by one-trial and multi-trial conditioning. A one-trial in vitro conditioning procedure consisting of light (CS) paired with the application of 5-HT results in the increased incorporation of 32PO4 into proteins detected with two-dimensional gel electrophoresis. Two of the phosphoproteins have molecular weights of 44 and 42 kDa, consistent with extracellular signal-regulated protein kinases (ERK1 and ERK2). Phosphorylation of the 44 and 42 kDa proteins by one-trial conditioning was inhibited by pretreatment with PD098059, A MEK1 (ERK-Activating kinase) inhibitor. Assays of ERK activity with brain myelin basic protein as a substrate revealed greater ERK activity for the group that received one-trial conditioning compared with an unpaired control group. Western blot analysis of phosphorylated ERK using antibodies recognizing the dually phosphorylated forms of ERK1 and ERK2 showed an increase in phosphorylation after one-trial conditioning compared with unpaired controls. The increased phosphorylation of ERK after one-trial conditioning was blocked by pretreatment with PD098059. Hermissenda that received 10 or 15 conditioning trials showed significant behavioral suppression compared with pseudo-random controls. After conditioning and behavioral testing, the conditioned animals showed significantly greater phosphorylation of ERK compared with the pseudo-random controls. These results show that the ERK-MAPK signaling pathway is activated in Pavlovian conditioning of Hermissenda.

  10. Finite-temperature Casimir pistons for an electromagnetic field with mixed boundary conditions and its classical limit

    Energy Technology Data Exchange (ETDEWEB)

    Teo, L P [Faculty of Information Technology, Multimedia University, Jalan Multimedia, Cyberjaya, 63100, Selangor Darul Ehsan (Malaysia)], E-mail: lpteo@mmu.edu.my

    2009-03-13

    In this paper, the finite-temperature Casimir force acting on a two-dimensional Casimir piston due to an electromagnetic field is computed. It was found that if mixed boundary conditions are assumed on the piston and its opposite wall, then the Casimir force always tends to restore the piston toward the equilibrium position, regardless of the boundary conditions assumed on the walls transverse to the piston. In contrast, if pure boundary conditions are assumed on the piston and the opposite wall, then the Casimir force always tends to pull the piston toward the closer wall and away from the equilibrium position. The nature of the force is not affected by temperature. However, in the high-temperature regime, the magnitude of the Casimir force grows linearly with respect to temperature. This shows that the Casimir effect has a classical limit as has been observed in other literature.

  11. Food-aversive classical conditioning increases a persistent sodium current in molluscan withdrawal interneurons in a transcription dependent manner.

    Science.gov (United States)

    Kiss, Tibor; Pirger, Zsolt; Kemenes, György

    2009-07-01

    In this study we examined changes in a persistent sodium current (I(NaP)) after behavioral aversive classical conditioning in the snail Helix pomatia. We trained animals by pairing food with a mild electric shock that triggered the whole-body withdrawal reflex. This aversive training resulted in transcription dependent long-term associative memory. Isolated central nervous system preparations were set up from trained, random control and naive animals and using two-electrode voltage clamp methods, I(NaP) was activated and measured in identified body withdrawal interneurons RPa3 and LPa3. We show here that in preparations from conditioned animals I(NaP) is increased, suggesting that modifications in intrinsic cellular properties contribute to the formation of the memory trace. Blocking RNA synthesis by systemic injection of actinomycin D (0.12microM) suppressed both memory consolidation in intact animals and the learning-induced increase of I(NaP) in withdrawal interneurons, suggesting that aversive classical conditioning affects sodium channel expression at the transcriptional level.

  12. Dendritic excitability microzones and occluded long-term depression after classical conditioning of the rabbit's nictitating membrane response.

    Science.gov (United States)

    Schreurs, B G; Tomsic, D; Gusev, P A; Alkon, D L

    1997-01-01

    We made intradendritic recordings in Purkinje cells (n = 164) from parasaggital slices of cerebellar lobule HVI obtained from rabbits given paired presentations of tone and periorbital electrical stimulation (classical conditioning, n = 27) or explicitly unpaired presentations of tone and periorbital stimulation (control, n = 16). Purkinje cell dendritic membrane excitability, assessed by the current required to elicit local dendritic calcium spikes, increased significantly in slices from animals that received classical conditioning. In contrast, membrane potential, input resistance, and amplitude of somatic and dendritic spikes were not different in slices from animals given paired or explicitly unpaired stimulus presentations. The location of cells with low thresholds for local dendritic calcium spikes suggested that there are specific sites for learning-related changes within lobule HVI. These areas may correspond to learning "microzones" and are consistent with locations of learning-related in vivo changes in Purkinje cell activity. Application of 4-aminopyridine, an antagonist of the rapidly inactivating potassium current IA, reduced the threshold for dendritic spikes in slices from naive animals to levels found in slices from trained animals. In cells where thresholds for eliciting parallel fiber-stimulated Purkinje cell excitatory postsynaptic potentials (EPSPs) were measured, levels of parallel fiber stimulation required to elicit a 6-mV EPSP as well as a 4-mV EPSP (n = 30) and a Purkinje cell spike (n = 56) were found to be significantly lower in slices from paired animals than unpaired controls. A classical conditioning procedure was simulated in slices of lobule HVI by pairing a brief, high-frequency train of parallel fiber stimulation (8 pulses, 100 Hz) with a brief, lower frequency train of climbing fiber stimulation (3 pulses, 20 Hz) to the same Purkinje cell. Following paired stimulation of the parallel and climbing fibers, Purkinje cell EPSPs

  13. Balanced plasticity and stability of the electrical properties of a molluscan modulatory interneuron after classical conditioning: a computational study

    Directory of Open Access Journals (Sweden)

    Dimitris Vavoulis

    2010-05-01

    Full Text Available The Cerebral Giant Cells (CGCs are a pair of identified modulatory interneurons in the Central Nervous System of the pond snail Lymnaea stagnalis with an important role in the expression of both unconditioned and conditioned feeding behavior. Following single-trial food-reward classical conditioning, the membrane potential of the CGCs becomes persistently depolarized. This depolarization contributes to the conditioned response by facilitating sensory cell to command neuron synapses, which results in the activation of the feeding network by the conditioned stimulus. Despite the depolarization of the membrane potential, which enables the CGGs to play a key role in learning-induced network plasticity, there is no persistent change in the tonic firing rate or shape of the action potentials, allowing these neurons to retain their normal network function in feeding. In order to understand the ionic mechanisms of this novel combination of plasticity and stability of intrinsic electrical properties, we first constructed and validated a Hodgkin-Huxley-type model of the CGCs. We then used this model to elucidate how learning-induced changes in a somal persistent sodium and a delayed rectifier potassium current lead to a persistent depolarization of the CGCs whilst maintaining their firing rate. Including in the model an additional increase in the conductance of a high-voltage-activated calcium current allowed the spike amplitude and spike duration also to be maintained after conditioning. We conclude therefore that a balanced increase in three identified conductances is sufficient to explain the electrophysiological changes found in the CGCs after classical conditioning.

  14. Whisker-signaled Eyeblink Classical Conditioning in Head-fixed Mice.

    Science.gov (United States)

    Lin, Carmen; Disterhoft, John; Weiss, Craig

    2016-03-30

    Eyeblink conditioning is a common paradigm for investigating the neural mechanisms underlying learning and memory. To better utilize the extensive repertoire of scientific techniques available to study learning and memory at the cellular level, it is ideal to have a stable cranial platform. Because mice do not readily tolerate restraint, they are usually trained while moving about freely in a chamber. Conditioned stimulus (CS) and unconditioned stimulus (US) information are delivered and eyeblink responses recorded via a tether connected to the mouse's head. In the head-fixed apparatus presented here, mice are allowed to run as they desire while their heads are secured to facilitate experimentation. Reliable conditioning of the eyeblink response is obtained with this training apparatus, which allows for the delivery of whisker stimulation as the CS, a periorbital electrical shock as the US, and analysis of electromyographic (EMG) activity from the eyelid to detect blink responses.

  15. The Effects of Two Forms of Physical Activity on Eyeblink Classical Conditioning

    Science.gov (United States)

    Green, John T.; Chess, Amy C.; Burns, Montana; Schachinger, Kira M.; Thanellou, Alexandra

    2011-01-01

    Voluntary exercise, in the form of free access to a running wheel in the home cage, has been shown to improve several forms of learning and memory. Acrobatic training, in the form of learning to traverse an elevated obstacle course, has been shown to induce markers of neural plasticity in the cerebellar cortex in rodents. In three experiments, we examined the effects of these two forms of physical activity on delay eyeblink conditioning in rats. In Experiment 1, exercising rats were given 17 days of free access to a running wheel in their home cage prior to 10 days of delay eyeblink conditioning. Rats that exercised conditioned significantly better and showed a larger reflexive eyeblink unconditioned response to the periocular stimulation unconditioned stimulus than rats that did not exercise. In Experiment 2, exercising rats were given 17 days of free access to a running wheel in their home cage prior to 10 days of explicitly unpaired stimulus presentations. Rats that exercised responded the same to tone, light, and periocular stimulation as rats that did not exercise. In Experiment 3, acrobatic training rats were given 15 days of daily training on an elevated obstacle course prior to 10 days of eyeblink conditioning. Activity control rats underwent 15 days of yoked daily running in an open field. Rats that underwent acrobatic training did not differ in eyeblink conditioning from activity control rats. The ability to measure the learned response precisely, and the well-mapped neural circuitry of eyeblink conditioning offer some advantages for the study of exercise effects on learning and memory. PMID:21238502

  16. The effects of two forms of physical activity on eyeblink classical conditioning.

    Science.gov (United States)

    Green, John T; Chess, Amy C; Burns, Montana; Schachinger, Kira M; Thanellou, Alexandra

    2011-05-16

    Voluntary exercise, in the form of free access to a running wheel in the home cage, has been shown to improve several forms of learning and memory. Acrobatic training, in the form of learning to traverse an elevated obstacle course, has been shown to induce markers of neural plasticity in the cerebellar cortex in rodents. In three experiments, we examined the effects of these two forms of physical activity on delay eyeblink conditioning in rats. In Experiment 1, exercising rats were given 17 days of free access to a running wheel in their home cage prior to 10 days of delay eyeblink conditioning. Rats that exercised conditioned significantly better and showed a larger reflexive eyeblink unconditioned response to the periocular stimulation unconditioned stimulus than rats that did not exercise. In Experiment 2, exercising rats were given 17 days of free access to a running wheel in their home cage prior to 10 days of explicitly unpaired stimulus presentations. Rats that exercised responded the same to tone, light, and periocular stimulation as rats that did not exercise. In Experiment 3, acrobatic training rats were given 15 days of daily training on an elevated obstacle course prior to 10 days of eyeblink conditioning. Activity control rats underwent 15 days of yoked daily running in an open field. Rats that underwent acrobatic training did not differ in eyeblink conditioning from activity control rats. The ability to measure the learned response precisely, and the well-mapped neural circuitry of eyeblink conditioning offer some advantages for the study of exercise effects on learning and memory.

  17. Comparison of a classical with a highly formularized body condition scoring system for dairy cattle

    OpenAIRE

    Isense, A.; Leiber, F.; Bieber, A.; Spengler, A.; Ivemeyer, S.; Maurer, V.; Klocke, Peter

    2014-01-01

    Body condition scoring is a common tool to assess the subcutaneous fat reserves of dairy cows. Because of its subjectivity, which causes limits in repeatability, it is often discussed controversially. Aim of the current study was to evaluate the impact of considering the cows overall appearance on the scoring process and on the validity of the results. Therefore, two different methods to reveal body condition scores (BCS), ‘independent BCS’ (iBCS) and ‘dependent BCS’ (dBCS), were used to asse...

  18. Revisiting olfactory classical conditioning of the proboscis extension response in honey bees: a step toward standardized procedures.

    Science.gov (United States)

    Matsumoto, Yukihisa; Menzel, Randolf; Sandoz, Jean-Christophe; Giurfa, Martin

    2012-10-15

    The honey bee Apis mellifera has emerged as a robust and influential model for the study of classical conditioning thanks to the existence of a powerful Pavlovian conditioning protocol, the olfactory conditioning of the proboscis extension response (PER). In 2011, the olfactory PER conditioning protocol celebrated its 50 years since it was first introduced by Kimihisa Takeda in 1961. In this protocol, individually harnessed honey bees are trained to associate an odor with sucrose solution. The resulting olfactory learning is fast and induces robust olfactory memories that have been characterized at the behavioral, neuronal and molecular levels. Despite the success of this protocol for studying the bases of learning and memory at these different levels, innumerable procedural variants have arisen throughout the years, which render comparative analyses of behavioral performances difficult. Moreover, because even slight variations in conditioning procedures may introduce significant differences in acquisition and retention performances, we revisit olfactory PER conditioning and define here a standardized framework for experiments using this behavioral protocol. To this end, we present and discuss all the methodological steps and details necessary for successful implementation of olfactory PER conditioning.

  19. Role of nitric oxide in classical conditioning of siphon withdrawal in Aplysia.

    Science.gov (United States)

    Antonov, Igor; Ha, Thomas; Antonova, Irina; Moroz, Leonid L; Hawkins, Robert D

    2007-10-10

    Nitric oxide (NO) is thought to be involved in several forms of learning in vivo and synaptic plasticity in vitro, but very little is known about the role of NO during physiological forms of plasticity that occur during learning. We addressed that question in a simplified preparation of the Aplysia siphon-withdrawal reflex. We first used in situ hybridization to show that the identified L29 facilitator neurons express NO synthase. Furthermore, exogenous NO produced facilitation of sensory-motor neuron EPSPs, and an inhibitor of NO synthase or an NO scavenger blocked behavioral conditioning. Application of the scavenger to the ganglion or injection into a sensory neuron blocked facilitation of the EPSP and changes in the sensory-neuron membrane properties during conditioning. Injection of the scavenger into the motor neuron reduced facilitation without affecting sensory neuron membrane properties, and injection of an inhibitor of NO synthase had no effect. Postsynaptic injection of an inhibitor of exocytosis had effects similar to injection of the scavenger. However, changes in the shape of the EPSP during conditioning were not consistent with postsynaptic AMPA-like receptor insertion but were mimicked by presynaptic spike broadening. These results suggest that NO makes an important contribution during conditioning and acts directly in both the sensory and motor neurons to affect different processes of facilitation at the synapses between them. In addition, they suggest that NO does not come from either the sensory or motor neurons but rather comes from another source, perhaps the L29 interneurons.

  20. A NECESSARY AND SUFFICIENT CONDITION FOR GLOBAL EXISTENCE OF CLASSICAL SOLUTIONS TO CAUCHY PROBLEM OF QUASILINEAR HYPERBOLIC SYSTEMS IN DIAGONAL FORM

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    This article considers Cauchy problem for quasilinear hyperbolic systems in diagonal form.A necessary and sufficient condition in guaranteeing that Cauchy problem admits a unique global classical solution on t 0 is obtained,and a sharp estimate of the life span for the classical solution is given.

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

    Science.gov (United States)

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

    2016-06-01

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

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

    Science.gov (United States)

    Baker, Kathryn D.; Richardson, Rick

    2015-01-01

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

  3. Autism and classical eyeblink conditioning: Performance changes of the conditioned response related to autism spectrum disorder diagnosis

    Directory of Open Access Journals (Sweden)

    John P Welsh

    2016-08-01

    Full Text Available Changes in the timing performance of conditioned responses (CRs acquired during trace and delay eyeblink conditioning (EBC are presented for diagnostic subgroups of children having autism spectrum disorder (ASD aged 6-15 years. Children diagnosed with autistic disorder (AD were analyzed separately from children diagnosed with either Asperger’s syndrome or Pervasive-developmental disorder not-otherwise-specified (Asp/PDD and compared to an age- and IQ-matched group of children that were typically developing (TD. Within-subject and between-groups contrasts in CR performance on sequential exposure to trace and delay EBC were analyzed to determine whether any differences would expose underlying functional heterogeneities of the cerebral and cerebellar systems in ASD subgroups. The EBC parameters measured were percentage CRs, CR onset latency, and CR peak latency. Neither AD nor Asp/PDD groups were impaired in CR acquisition during trace or delay EBC. AD and Asp/PDD both altered CR timing, but not always in the same way. Although the AD group showed normal CR timing during trace EBC, the Asp/PDD group showed a significant 27 and 28 ms increase in CR onset and peak latency, respectively, during trace EBC. In contrast, the direction of the timing change was opposite during delay EBC, during which the Asp/PDD group showed a significant 29 ms decrease in CR onset latency and the AD group showed a larger 77 ms decrease in CR onset latency. Only the AD group showed a decrease in CR peak latency during delay EBC, demonstrating another difference between AD and Asp/PDD. The difference in CR onset latency during delay EBC for both AD and Asp/PDD was due to an abnormal prevalence of early onset CRs that were intermixed with CRs having normal timing, as observed both in CR onset histograms and mean CR waveforms. In conclusion, significant heterogeneity in EBC performance was apparent within diagnostic groups, and this may indicate that EBC performance can

  4. Sensory prediction or motor control? Application of Marr-Albus type models of cerebellar function to classical conditioning

    Directory of Open Access Journals (Sweden)

    Nathan F Lepora

    2010-10-01

    Full Text Available Marr-Albus adaptive filter models of the cerebellum have been applied successfully to a range of sensory and motor control problems. Here we analyze their properties when applied to classical conditioning of the nictitating membrane response in rabbits. We consider a system-level model of eyeblink conditioning based on the anatomy of the eyeblink circuitry, comprising an adaptive filter model of the cerebellum, a comparator model of the inferior olive and a linear dynamic model of the nictitating membrane plant. To our knowledge, this is the first model that explicitly includes all these principal components, in particular the motor plant that is vital for shaping and timing the behavioral response. Model assumptions and parameters were systematically investigated to disambiguate basic computational capacities of the model from features requiring tuning of properties and parameter values. Without such tuning, the model robustly reproduced a range of behaviors related to sensory prediction, by displaying appropriate trial-level associative learning effects for both single and multiple stimuli, including blocking and conditioned inhibition. In contrast, successful reproduction of the real-time motor behavior depended on appropriate specification of the plant, cerebellum and comparator models. Although some of these properties appear consistent with the system biology, fundamental questions remain about how the biological parameters are chosen if the cerebellar microcircuit applies a common computation to many distinct behavioral tasks. It is possible that the response profiles in classical conditioning of the eyeblink depend upon operant contingencies that have previously prevailed, for example in naturally occurring avoidance movements.

  5. Fears and Phobias

    Science.gov (United States)

    ... A Week of Healthy Breakfasts Shyness Fears and Phobias KidsHealth > For Teens > Fears and Phobias Print A ... help and support to overcome them. previous continue Phobias A phobia is an intense fear reaction to ...

  6. Expectancy-learning and evaluative learning in human classical conditioning: affective priming as an indirect and unobtrusive measure of conditioned stimulus valence.

    Science.gov (United States)

    Hermans, Dirk; Vansteenwegen, Debora; Crombez, Geert; Baeyens, Frank; Eelen, Paul

    2002-03-01

    It has been argued that in classical conditioning two processes might be operative. First, one may learn that the conditioned stimulus (CS+) is a valid predictor for the occurrence of the biologically negative or positive event (US; expectancy-learning). Second, one may learn to perceive the conditioned stimulus itself as a negative or positive stimulus, depending on the valence of the event it has been associated with (evaluative learning). Until the present, however, both forms of learning have been investigated using rather different conditioning procedures. Using a differential aversive conditioning preparation with pictures of human faces as CSs and an electrocutaneous stimulus as US, we were able to demonstrate that both forms of learning can co-occur. Moreover, the extent of evaluative learning in this aversive conditioning procedure did not significantly differ from the amount of evaluative learning in an evaluative conditioning procedure with positive and negative adjectives as USs, which was administered to the same participants. In the present study evaluative learning was not only indexed by direct evaluative ratings, but we introduced affective priming as an indirect and unobtrusive, reaction time based measure of stimulus valence. Finally, imagery instructions during acquisition did not facilitate expectancy-learning nor evaluative learning.

  7. Fear and aggression in dogs

    Directory of Open Access Journals (Sweden)

    Uzunova Krasimira

    2011-11-01

    Full Text Available In this review, the concepts of fear, phobia and aggression in dogs were precisely defined, as well as their underlying causes. The behavioural activities specific for these conditions were indicated. The accompanying symptoms were consistently explained. The causes that the development of pathological fear leads to aggression in dogs as well as the ex various therapy options depending on the clinical signs were presented.

  8. Comparison of a classical with a highly formularized body condition scoring system for dairy cattle.

    Science.gov (United States)

    Isensee, A; Leiber, F; Bieber, A; Spengler, A; Ivemeyer, S; Maurer, V; Klocke, P

    2014-12-01

    Body condition scoring is a common tool to assess the subcutaneous fat reserves of dairy cows. Because of its subjectivity, which causes limits in repeatability, it is often discussed controversially. Aim of the current study was to evaluate the impact of considering the cows overall appearance on the scoring process and on the validity of the results. Therefore, two different methods to reveal body condition scores (BCS), 'independent BCS' (iBCS) and 'dependent BCS' (dBCS), were used to assess 1111 Swiss Brown Cattle. The iBCS and the dBCS systems were both working with the same flowchart with a decision tree structure for visual and palpatory assessment using a scale from 2 to 5 with increment units of 0.25. The iBCS was created strictly complying with the defined frames of the decision tree structure. The system was chosen due to its formularized approach to reduce the influence of subjective impressions. By contrast, the dBCS system, which was in line with common practice, had a more open approach, where - besides the decision tree - the overall impression of the cow's physical appearance was taken into account for generating the final score. Ultrasound measurement of the back fat thickness (BFT) was applied as a validation method. The dBCS turned out to be the better predictor of BFT, explaining 67.3% of the variance. The iBCS was only able to explain 47.3% of the BFT variance. Within the whole data set, only 31.3% of the animals received identical dBCS and iBCS. The pin bone region caused the most deviations between dBCS and iBCS, but also assessing the pelvis line, the hook bones and the ligaments led to divergences in around 20% of the scored animals. The study showed that during the assessment of body condition a strict adherence to a decision tree is a possible source of inexact classifications. Some body regions, especially the pin bones, proved to be particularly challenging for scoring due to difficulties in assessing them. All the more, the inclusion

  9. Odor discrimination in classical conditioning of proboscis extension in two stingless bee species in comparison to Africanized honeybees.