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PubMed2006

Effects of repeated acquisitions and extinctions on response rate and pattern.

The procedure developed by R. A. Rescorla (2002) was used to study the effects of repeated acquisitions and extinctions of head entry responses into a food cup by rats. In each of 4 20-session phases, food was delivered at the end of particular 30-s auditory and visual stimuli, but not at the end of different 30-s auditory and visual stimuli. Based on response rates to individual stimuli and compound stimuli, the increase in response rate in acquisition occurred more rapidly than the decrease in extinction. Acquisition, but not extinction, occurred faster after successive transitions between acquisition and extinction. Temporal gradients of responding developed during acquisition and remained during extinction. Conclusions based on mean response rate, temporal gradients, and transfer tests were consistent.

Acoustic Stimulation↗
PubMed2006

Context switch effects on acquisition and extinction in human predictive learning.

Four experiments tested context switch effects on acquisition and extinction in human predictive learning. A context switch impaired probability judgments about a cue-outcome relationship when the cue was trained in a context in which a different cue underwent extinction. The context switch also impaired judgments about a cue trained in a context different from the extinction context, whenever this training was concurrent with extinction of another cue. After extinction, new cue-outcome relationships learned, even in a different task, became context specific. Moreover, renewal was consistently observed. It is suggested that context switch effects result from a process by which ambiguity leads participants to attend to the contexts.

Adolescent↗
PubMed2003

Extinction, renewal, and spontaneous recovery of a spatial preference in the water maze.

Four experiments with C57BL/6 mice investigated extinction of a spatial preference in the Morris water maze. In Experiment 1, a spatial preference was extinguished by exposing mice to the water maze in the absence of a platform but in the presence of the distal spatial cues. In Experiment 2, extinction occurred when the platform was removed from the pool, when it was presented in random locations, or when it was presented consistently in the opposite location. Contextual renewal (Experiment 3) and spontaneous recovery (Experiment 4) of spatial preferences argue against an interpretation of extinction in terms of unlearning and instead suggest that extinction in the water maze, like extinction in Pavlovian conditioning, suppresses the original association. Implications of these findings for theories of spatial learning and hippocampal function are discussed.

Animals↗
PubMed2005

The midbrain periaqueductal gray and fear extinction: opioid receptor subtype and roles of cyclic AMP, protein kinase A, and mitogen-activated protein kinase.

Four experiments studied the opioid receptor subtype and signal transduction mechanisms mediating fear extinction in the ventrolateral quadrant of the midbrain periaqueductal gray (vlPAG). Microinjection of a mu- but not a delta- or kappa-opioid receptor antagonist into the vlPAG retarded extinction. Extinction was also dose-dependently retarded by vlPAG infusions of a cyclic AMP (cAMP) analog but was unaffected by infusions of a protein kinase A activator or a mitogen-activated protein kinase inhibitor across wide dose ranges. The results show that fear extinction occurs via activation of vlPAG mu-opioid receptors and involves reductions in cAMP. These mechanisms are different from the cellular mechanisms for extinction in the amygdala and from the known cellular mechanisms for opioid analgesia in the vlPAG.

Analysis of Variance↗
PubMed2006

D-cycloserine facilitates extinction but does not eliminate renewal of the conditioned emotional response.

The effect of D-cycloserine (DCS), an NMDA partial agonist, on extinction of fear was investigated in rats using the conditioned emotional response preparation. Fear extinction was facilitated when the first 4 trials occurred with a 30-mg/kg dose of DCS. However, extinguished fear was "renewed" regardless of the drug treatment when the rats were returned to the context in which fear had been conditioned. Additional results suggest that DCS's facilitation of extinction is a small but meaningful effect in the current method. The results suggest caution regarding the use of DCS as an adjunct to extinction: Although the drug may modestly facilitate extinction learning, it does not necessarily destroy the potential for relapse. Behavioral mechanisms are discussed.

Animals↗
PubMed1979

Modulation of behavioral inhibition in appetitive extinction following manipulation of adrenal steroids in rats: implications for involvement of the hippocampus.

Corticosterone, the principal glucocorticoid in the rat, binds selectively to the CA1 pyramidal neurons of the hippocampus where the hormone has been demonstrated to exert a moderate chronic suppression of spontaneous activity. In the first experiment of the current study, the functional behavioral significance of this hormone--brain interaction was investigated in the extinction of an appetitive runway response in normal rats and those with lesions of the hippocampus. During extinction, half of the animals in each group were given daily subcutaneous injections of corticosterone. Whie the classical retardation effect of hippocampal lesions on appetitive extinction was replicated, hormone treatment was without effect in normal or hippocampally damaged subjects. The absence of a hormone effect in normals was primarily attributed to a saturated limited-binding system operating in the normal animal. Experiment 2 tested this notion, repeating the first experiment, with adrenal-ectomized (ADX), ADX + corticosterone replacement, and normal groups of animals. Adrenalectomy produced a striking facilitation of extinction which was speculated to be the result of a hyperactive inhibitory neural organ free from an inhibitory endocrine feedback. Corticosterone treatment normalized the progress of extinction in ADX animals, providing support for the afore-mentioned speculation. In the normal animal, it appears that a stress-induced surge in hormone level interacts with a limited-capacity neural binding to produce a transient dynamic range of behavioral disinhibition, perhaps promoting persistence during initial stages of frustrative nonreward in moderate stress tasks.

Animals↗
PubMed2002

Prefrontocortical dopamine loss in rats delays long-term extinction of contextual conditioned fear, and reduces social interaction without affecting short-term social interaction memory.

Prefrontal dopamine loss delays extinction of cued fear conditioning responses, but its role in contextual fear conditioning has not been explored. Medial prefrontal lesions also enhance social interaction in rats, but the role of prefrontal dopamine loss on social interaction memory is not known. Besides, a role for subcortical accumbal dopamine on mnesic changes after prefrontal dopamine manipulation has been proposed but not explored. The objective was to study the involvement of dopaminergic neurotransmission in the medial prefrontal cortex (mPFC) and nucleus accumbens in two mnesic tasks: contextual fear conditioning and social interaction memory. For contextual fear conditioning, short- and long-term freezing responses after an electric shock were studied, as well as extinction retention. Regarding social interaction memory, the recognition of a juvenile, a very sensitive short-term memory test, was used. Dopamine loss was carried out by injection of 6-hydroxydopamine, and postmortem catecholamine levels were analyzed by high-performance liquid chromatography. Prefrontocortical dopamine loss (>76%) led to a reactive enhancement of accumbal dopamine content (p<0.01), supporting the hypothesis that a hyperdopaminergic tone emerges in the nucleus accumbens after prefrontocortical dopamine loss. In lesioned rats, long-term extinction of contextual fear conditioning was significantly delayed and extinction retention was impaired without changes in acquisition and short-term contextual fear conditioning and, on the other hand, acquisition and short-term social interaction memory were not affected, although time spent on social interaction was significantly reduced. Added dopamine loss in the nucleus accumbens (>76%) did not alter these behavioral changes. In summary, the results of the present study indicate that the dopaminergic network in the mPFC (but not in the nucleus accumbens) coordinates the normal long-term extinction of contextual fear conditioning responses without affecting their acquisition, and it is involved in time spent on social interaction, but not acquisition and short-term social interaction memory.

Animals↗
PubMed2002

Climate change hastens population extinctions.

Climate change is expected to alter the distribution and abundance of many species. Predictions of climate-induced population extinctions are supported by geographic range shifts that correspond to climatic warming, but few extinctions have been linked mechanistically to climate change. Here we show that extinctions of two populations of a checkerspot butterfly were hastened by increasing variability in precipitation, a phenomenon predicted by global climate models. We model checkerspot populations to show that changes in precipitation amplified population fluctuations, leading to rapid extinctions. As populations of checkerspots and other species become further isolated by habitat loss, climate change is likely to cause more extinctions, threatening both species diversity and critical ecosystem services.

Animals↗
PubMed2006

Recent fear is resistant to extinction.

In some individuals, fearful experiences (e.g., combat) yield persistent and debilitating psychological disturbances, including posttraumatic stress disorder (PTSD). Early intervention (e.g., debriefing) after psychological trauma is widely practiced and argued to be an effective strategy for limiting subsequent psychopathology, although there has been considerable debate on this point. Here we show in an animal model of traumatic fear that early intervention shortly after an aversive experience yields poor long-term fear reduction. Extinction trials administered minutes after aversive fear conditioning in rats suppressed fear acutely, but fear suppression was not maintained the next day. In contrast, delivering extinction trials 1 day after fear conditioning produced an enduring suppression of fear memory. We further show that the recent experience of an aversive event, not the timing of the extinction intervention per se, inhibits the development of long-term fear extinction. These results reveal that the level of fear present at the time of intervention is a critical factor in the efficacy of extinction. Importantly, our work suggests that early intervention may not yield optimal outcomes in reducing posttraumatic stress, particularly after severe trauma.

Animals↗
PubMed2002

Extinction of the soleus H reflex induced by conditioning stimulus given after test stimulus.

OBJECTIVE: To quantify the extinction of the soleus H reflex induced by a conditioning stimulus above the motor threshold to the post-tibial nerve applied 10-12 ms after a test stimulus (S2 method). METHODS: Ten healthy subjects participated. The sizes of extinction induced by a test stimulus above the motor threshold (conventional method) and by the S2 method were measured. RESULTS: The size of the conditioned H reflex decreased as the intensity of the S2 conditioning stimulus increased. The decrease was less than that induced by the conventional method. The difference between the two methods correlated highly with the amount of orthodromically activated recurrent inhibition. When the S2 conditioning stimulus evoked an M wave that was roughly half of the maximum M wave, the decrease in the size of the conditioned H reflex depended on the size of the unconditioned H reflex. CONCLUSION: The S2 method allows us to observe extinction without changing the intensity of the test stimulus. The amount of the extinction depends partially on the size of the unconditioned H reflex. The difference in the sizes of extinction between the S2 and conventional methods should relate to recurrent inhibition.

Adolescent↗
PubMed2000

Recent and remote extinction cues reduce spontaneous recovery.

Five appetitive conditioning experiments with rats examined the ability of extinction cues (ECs) to reduce spontaneous recovery after extinction procedures that varied the temporal relation between the ECs and the conditioned stimulus (CS) and included presentations of additional events (e.g. other stimuli correlated with extinction, CSs, and the US). In extinction, two different ECs were presented either closely in time before (i.e. recent to), or more distant (i.e. remote) from a nonreinforced CS. Both recent and remote ECs reduced spontaneous recovery to the CS when present during testing (Experiments 1-4). Each EC reduced recovery despite the addition during extinction of a second EC and CS (Experiments 1, 3, and 4), and the US (Experiment 3). Experiments 4 and 5 investigated the recent and remote ECs' tendency to control a serial occasion setting discrimination involving the target CS under explicit training conditions. Neither EC gained such discriminative control. Possible explanations of the results are discussed, including configural learning, occasion setting, and contextual cue control.

Animals↗
PubMed2000

Left tactile extinction following visual stimulation of a rubber hand.

In close analogy with neurophysiological findings in monkeys, neuropsychological studies have shown that the human brain constructs visual maps of space surrounding different body parts. In right-brain-damaged patients with tactile extinction, the existence of a visual peripersonal space centred on the hand has been demonstrated by showing that cross-modal visual-tactile extinction is segregated mainly in the space near the hand. That is, tactile stimuli on the contralesional hand are extinguished more consistently by visual stimuli presented near the ipsilesional hand than those presented far from it. Here, we report the first evidence in humans that this hand-centred visual peripersonal space can be coded in relation to a seen rubber replica of the hand, as if it were a real hand. In patients with left tactile extinction, a visual stimulus presented near a seen right rubber hand induced strong cross-modal visual-tactile extinction, similar to that obtained by presenting the same visual stimulus near the patient's right hand. Critically, this specific cross-modal effect was evident when subjects saw the rubber hand as having a plausible posture relative to their own body (i.e. when it was aligned with the subject's right shoulder). In contrast, cross-modal extinction was strongly reduced when the seen rubber hand was arranged in an implausible posture (i. e. misaligned with respect to the subject's right shoulder). We suggest that this phenomenon is due to the dominance of vision over proprioception: the system coding peripersonal space can be 'deceived' by the vision of a fake hand, provided that its appearance looks plausible with respect to the subject's body.

Aged↗
PubMed2000

A systematic study of visual extinction. Between- and within-field deficits of attention in hemispatial neglect.

Mechanisms of visual extinction were investigated in four patients with right hemisphere damage using a partial report paradigm. Different shapes (star or triangle) were displayed in one, two or four possible locations so that double simultaneous stimuli occurred either across the two hemifields or within the same hemifield. Patients attended either to the location (right, left or both), number (one, two or four) or shape (no, one or two stars among the shapes presented) of stimuli in three separate experiments using the same displays and exposure duration. Reporting the location (Experiment 1) produced marked contralesional extinction, although reaction time was delayed compared with unilateral right trials, indicating unconscious processing. Reaction time was also delayed on correct bilateral and unilateral left trials. In contrast, enumerating stimuli (Experiment 2) caused no significant contralesional extinction on bilateral displays and reaction time was similar on bilateral and unilateral right trials, suggesting that information from both fields was grouped in a single numerable percept in this task. However, patients often detected only one of two stimuli within the left field. Whereas similarity of shapes improved localization and did not affect enumeration, identifying stars among shapes (Experiment 3) revealed a severe inability to detect two similar targets between hemifields as well as within each of the hemifields. Distracting triangles were generally less detrimental to the perception of a concurrent target on either side, but slowed the reaction time regardless of whether they were in the same or the opposite field. Relative difficulty in ignoring distractors correlated with neglect severity on a cancellation task, and was most prominent in one patient with a large amount of frontal damage. These findings suggest that (i) allocation of attention to identical stimuli can be modulated by task demand; (ii) enumerating a small set of items across fields may not require attending to individual stimuli but relies on preattentive subitizing ability, as found in normal subjects; (iii) location information may be critical for attentional mechanisms subserved by the parietal cortex and pathological competition for awareness in extinction; (iv) extinction entails a bilateral deficit in attending to two concurrent similar targets when their features must be identified; and (v) the relevance of the stimuli can modulate the distribution of attention, possibly through frontal top-down control. These findings are consistent with recent neurophysiological evidence of parietal and frontal attentional influences on ventral visual pathways.

Aged↗
PubMed2001

Auditory peripersonal space in humans: a case of auditory-tactile extinction.

Animal experiments have shown that the spatial correspondence between auditory and tactile receptive fields of ventral pre-motor neurons provides a map of auditory peripersonal space around the head. This allows neurons to localize a near sound with respect to the head. In the present study, we demonstrated the existence of an auditory peripersonal space around the head in humans. In a right-brain damaged patient with tactile extinction, a sound delivered near the ipsilesional side of the head extinguished a tactile stimulus delivered to the contralesional side of the head (cross-modal auditory-tactile extinction). In contrast, when an auditory stimulus was presented far from the head, cross-modal extinction was dramatically reduced. This spatially specific cross-modal extinction was found only when a complex sound like a white noise burst was presented; pure tones did not produce spatially specific cross-modal extinction. These results show a high degree of functional similarity between the characteristics of the auditory peripersonal space representation in humans and monkeys. This similarity suggests that analogous physiological substrates might be responsible for coding this multisensory integrated representation of peripersonal space in human and non-human primates.

Aged↗
PubMed2006

Effects of environmental enrichment on extinction and reinstatement of amphetamine self-administration and sucrose-maintained responding.

The current experiments aimed to determine whether differential rearing alters extinction and/or reinstatement of amphetamine self-administration or sucrose-maintained responding. Male Sprague-Dawley rats were raised in either an enriched condition or an isolated condition. Rats were then trained to lever press on a continuous reinforcement schedule across either 15 daily amphetamine self-administration sessions or 15 sucrose-reinforced sessions, followed by 10 sessions of extinction. After the extinction sessions, priming doses of amphetamine (0, 0.25 or 1.0 mg/kg) were administered 15 min before the session, or sucrose (one or 10 pellets) was delivered non-contingently at the beginning of the session. Enriched condition rats showed greater extinction for amphetamine and sucrose-maintained responding than isolated condition rats. When primed with amphetamine, isolated condition rats reinstated responding following 0.25 mg/kg of amphetamine, whereas enriched condition rats only reinstated responding after 1.0 mg/kg of amphetamine. Isolated condition rats failed to reinstate responding following sucrose delivery, while enriched condition rats reinstated responding following the delivery of 10 sucrose pellets. These results indicate that environmental enrichment enhanced the extinction of both amphetamine and sucrose-maintained responding. Environmental enrichment also raised the reinstatement threshold specific to the amphetamine prime, suggesting a reduction in the incentive motivational effect of amphetamine.

Amphetamine↗
PubMed2006

Modelling the extinction of Steller's sea cow.

Steller's sea cow, a giant sirenian discovered in 1741 and extinct by 1768, is one of the few megafaunal mammal species to have died out during the historical period. The species is traditionally considered to have been exterminated by 'blitzkrieg'-style direct overharvesting for food, but it has also been proposed that its extinction resulted from a sea urchin population explosion triggered by extirpation of local sea otter populations that eliminated the shallow-water kelps on which sea cows fed. Hunting records from eighteenth century Russian expeditions to the Commander Islands, in conjunction with life-history data extrapolated from dugongs, permit modelling of sea cow extinction dynamics. Sea cows were massively and wastefully overexploited, being hunted at over seven times the sustainable limit, and suggesting that the initial Bering Island sea cow population must have been higher than suggested by previous researchers to allow the species to survive even until 1768. Environmental changes caused by sea otter declines are unlikely to have contributed to this extinction event. This indicates that megafaunal extinctions can be effected by small bands of hunters using pre-industrial technologies, and highlights the catastrophic impact of wastefulness when overexploiting resources mistakenly perceived as 'infinite'.

Animals↗
PubMedDate not supplied

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

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

Animals↗
PubMedDate not supplied

Facilitation of memory for extinction of drug-induced conditioned reward: role of amygdala and acetylcholine.

These experiments examined the effects of posttrial peripheral and intra-amygdala injections of the cholinergic muscarinic receptor agonist oxotremorine on memory consolidation underlying extinction of amphetamine conditioned place preference (CPP) behavior. Male Long-Evans rats were initially trained and tested for an amphetamine (2 mg/kg) CPP. Rats were subsequently given limited extinction training, followed by immediate posttrial peripheral or intrabasolateral amygdala injections of oxotremorine. A second CPP test was then administered, and the amount of time spent in the previously amphetamine-paired and saline-paired apparatus compartments was recorded. Peripheral (0.07 or 0.01 mg/kg) or intra-amygdala (10 etag/0.5 microL) postextinction trial injections of oxotremorine facilitated CPP extinction. Oxotremorine injections that were delayed 2 h posttrial training did not enhance CPP extinction, indicating a time-dependent effect of the drug on memory consolidation processes. The findings indicate that memory consolidation for extinction of approach behavior to environmental stimuli previously paired with drug reward can be facilitated by posttrial peripheral or intrabasolateral amygdala administration of a cholinergic agonist.

Acetylcholine↗