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PubMedDate not supplied

Mismatch between what is expected and what actually occurs triggers memory reconsolidation or extinction.

In previous experiments on contextual memory, we proposed that the unreinforced re-exposure to the learning context (conditioned stimulus, CS) acts as a switch guiding the memory course toward reconsolidation or extinction, depending on reminder duration. This proposal implies that the system computes the total exposure time to the context, from CS onset to CS offset, and therefore, that the reminder presentation must be terminated for the switching mechanism to become operative. Here we investigated to what extent this requirement is necessary, and we explored the relation between diverse phases in the reconsolidation and extinction processes. We used the contextual memory model of the crab Chasmagnathus which involves an association between the learning context (CS) and a visual danger stimulus (unconditioned stimulus, US). Administration of cycloheximide was used to test the lability state of memory at different time points. The results show that two factors, no-reinforcement during the reminder (i.e., CS re-exposure) and CS offset are the necessary conditions for both processes to occur. Regardless of the reminder duration, memory retrieved by unreinforced CS re-exposure emerges intact and consolidated when tested before CS offset, suggesting that neither reconsolidation nor extinction is concomitant with CS re-exposure. Either process could only be triggered once the definitive mismatch between CS and US is confirmed by CS termination without the expected reinforcement.

Animals↗
PubMedDate not supplied

Cognitive processes in extinction.

Human conditioning research shows that learning is closely related to consciously available contingency knowledge, requires attentional resources, and is influenced by language. This research suggests a cognitive model in which extinction consists of changes in contingency beliefs in long-term memory. Laboratory and clinical evidence on extinction is briefly reviewed, and it is concluded that the evidence supports the cognitive position. There is little evidence for a separate, noncognitive conditioning system. The primary implication for neural analysis is that learning and extinction are unlikely to be reducible to direct connections in which one stimulus simply activates or inhibits the memory representation of another. Rather, an adequate neural model will involve the integration of both low-level and high-level systems, including attention, representation of stimulus relations in long-term memory, and a dynamic performance mechanism based on anticipation, not just activation.

Animals↗
PubMedDate not supplied

The L-type calcium channel blocker nifedipine impairs extinction, but not reduced contingency effects, in mice.

We recently reported that fear extinction, a form of inhibitory learning, is selectively blocked by systemic administration of L-type voltage-gated calcium channel (LVGCC) antagonists, including nifedipine, in mice. We here replicate this finding and examine three reduced contingency effects after vehicle or nifedipine (40 mg/kg) administration. In the first experiment, contingency reduction was achieved by adding USs to the training protocol (degraded contingency), a phenomenon thought to be independent of behavioral inhibition. In the second experiment, contingency reduction was achieved by varying the percentage of CS-US pairing, a phenomenon thought to be weakly dependent on behavioral inhibition. In the third and fourth experiments, contingency reduction was achieved by adding CSs to the training protocol (partial reinforcement), a phenomenon thought to be completely dependent on behavioral inhibition. We found that none of these reduced contingency effects was impaired by nifedipine. In a final experiment, we found that extinction conducted 1 or 3 h post-acquisition, but not immediately, was LVGCC-dependent. Taken together, the results suggest that reduced contingency effects and extinction depend on different molecular mechanisms and that LVGCC dependence of behavioral inhibition develops with time after associative CS-US learning.

Animals↗
PubMed2004

Amygdalar circuits required for either consolidation or extinction of taste aversion memory are not required for reconsolidation.

Recent reports have revitalized the debate on whether, for each item in memory, consolidation occurs just once, or whether, upon their activation in retrieval, items in memory undergo reconsolidation. Further, it has been recently reported that following retrieval in the absence of reinforcer, the activated memory can either reconsolidate or extinguish, depending on the training history. This raises the question whether consolidation, extinction and reconsolidation share neuronal mechanisms, and moreover, whether reconsolidation recapitulates consolidation. In conditioned taste aversion (CTA), consolidation depends on protein synthesis in the central nucleus of the amygdala, whereas extinction depends on protein synthesis in the basolateral nuclei of the amygdala. Here we show that inhibition of protein synthesis in either of these nuclei has no effect on CTA memory under conditions that initiate reconsolidation. This implies that reconsolidation does not recapitulate consolidation, and that consolidation, reconsolidation and extinction are different processes.

Amygdala↗
PubMed1976

Resistance to extinction as a function of IQ and reinforcement ratio among retarded children.

Children at three levels of mental retardation (IQ ranges of 50-60, 30-40 and 20-below) were trained to bar-press on one of two variable ratio (V.R.) schedules. Responses were reinforced twenty-five times on either a V.R.2 or V.R.4 schedule. Analysis of the number of responses during extinction indicated an inverse relationship between IQ and resistance to extinction. The period reinforcement extinction effect was found, but there was no interaction with IQ level. The results support the position that inhibitory control is an important parameter along which intelligence may be ordered.

Child↗
PubMed1991

Paradox, reprimand and extinction in adults with mental handicap.

To assess the efficacy of paradoxical directives, levels of challenging behaviour during 2 weeks of paradox, reprimand and extinction were compared with baseline levels in four adults with mental handicaps attending a day centre. Paradox was the most effective procedure for reducing the frequency and severity of challenging behaviour by an average of over 70% by the end of 2 weeks and up to 90% in certain subjects; extinction was least effective. Paradox was most effective with more defiant subjects, when staff rated treatment success as low, when improvement using extinction and reprimand was poorest, and in reducing aggressive behaviour. The present authors suggest the overjustification effect offers an explanation for the effects of paradox.

Adolescent↗
PubMed1997

Left hemisphere advantage for classical conditioning to auditory verbal CSs: effects of nonattended extinction.

The effects of brain laterality, or hemispheric asymmetry, on electrodermal classical conditioning during both attended and nonattended stimulus conditions were studied. Participants were conditioned to consonant-vowel (CV) syllables during an acquisition, or learning, phase of the experiment. During a subsequent extinction phase, the conditioned stimuli (CS) were presented in a dichotic mode of presentation. Half of the participants attended to the left ear (right hemisphere) during the extinction phase and the other half of the participants attended to the right ear (left hemisphere). The results showed effects of conditioning for all participants during the acquisition phase. During dichotic extinction, the left hemisphere group showed remaining learning effects in both the attended and nonattended conditions, whereas the right hemisphere group demonstrated conditioning only in the attended condition.

Acoustic Stimulation↗
PubMed1997

Psychophysiological response of ADHD children to reward and extinction.

In this study, we examined heart rate and skin conductance levels of 18 children with attention-deficit hyperactivity disorder (ADHD) and 18 normal children as they performed a repetitive motor task during reward and extinction conditions. Fowles (1980, Psychophysiology, 17, 87-104; 1988, Psychophysiology, 25, 373-391) suggested that psychophysiological responsivity reflects activity in two of Gray's (1982, The neuropsychology of anxiety, Oxford University Press; 1987, The psychology of fear and stress, Cambridge University Press) motivational systems; heart rate reactivity during reward reflects activity in the behavioral activation system, and skin conductance reactivity during extinction reflects activity in the behavioral inhibition system. As predicted, control children showed increased heart rate when reward was present and increased skin conductance when reward was removed. Compared with controls, ADHD children failed to show increased skin conductance levels during extinction, suggesting a weak behavioral inhibition system. ADHD children also displayed faster heart rate habituation to reward.

Adolescent↗
PubMed1979

Personality and extinction of a conditioned electrodermal response.

This study investigated personality differences in extinction of a conditioned EDR. The subjects were selected on the basis of EPI neuroticism and impulsivity scores. Subjects with scores on, or near, the sample means were excluded. Fifty-one subjects underwent an aversive discrimination conditioning procedure. The reinforcement was 75 per cent, the UCS was 100 dB white noise for 1 sec, while the CS was one of five different coloured lights of 2 sec duration. The UCS was presented at CS termination. Subjects were informed of the CS--UCS contingency before the acquisition phase and informed of the onset of the extinction phase. Subjects high on impulsivity showed significantly (P less than 0.01) greater extinction of the discrimination than subjects low on impulsivity.

Conditioning, Classical↗
PubMed1962

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

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

Brain↗
PubMed1969

Olfactory stimuli and the "pseudo-extinction" effect.

Continuously rewarded rats show a decrease in running speed on a runway recently traversed by other rats undergoing experimental extinction. This "pseudo-extinction" effect is caused by discriminable odors emitted by extinction subjects. These odors could be confounding variables in studies using forms of aversive stimulation.

Animals↗
PubMed1986

Interpretation of abnormal responses to the Quality Extinction Test in schizophrenia.

The Quality Extinction Test (QET) has proved to be valuable for detecting abnormal hemisphere functioning in neurological as well as psychiatric patients. The present and other studies have shown a higher frequency of left side extinction in schizophrenics. This has been attributed either to contralateral parietal malfunction or to ipsilateral frontal abnormality. To evaluate the role of different brain regions in determining tactile extinctions in schizophrenic patients, a population of 70 such subjects were subgrouped according to their QET scores (left, right, left/right, and non-extinguishers) and their neuropsychological task performance profiles were compared. Right extinguishers had QET scores similar to those of non-extinguishers; left/right extinguishers were closer to left extinguishers. Non-extinguishers were the best performers and left extinguishers the poorest, particularly where right hemisphere-dependent tasks were concerned.

Adult↗
PubMed1998

Tactile salience influences extinction.

We delivered unilateral (left or right) or bilateral tactile stimuli to hands or feet of right-brain-damaged patients, six with tactile extinction and two without. Stimuli were simple touches or sliding stimuli directed proximo-distally (e.g., toward the fingers) or disto-proximally (e.g., toward the forearm). Patients were asked to report number (one or two), type (touch or slide), and direction (proximo-distally or disto-proximally) of the experimental stimuli. Nonextinction patients performed perfectly. Extinction patients, although accurate in reporting single stimuli, omitted left stimuli under double-stimuli conditions. However, the number of left stimuli detected consciously was related to an imbalance of the salience between left and right stimuli. Moreover, in three patients the extinguished, left-sided stimulus, even when inaccessible to consciousness, influenced implicitly the report of the features of the right stimulus. Thus, the relationships between left and right stimuli can modulate both overtly and covertly the performance of extinction patients.

Adolescent↗
PubMed2006

Repeated cocaine effects on learning, memory and extinction in the pond snail Lymnaea stagnalis.

The persistence of drug addiction suggests that drugs of abuse enhance learning and/or impair extinction of the drug memory. We studied the effects of repeated cocaine on learning, memory and reinstatement in the pond snail, Lymnaea stagnalis. Respiratory behavior can be operantly conditioned and extinguished in Lymnaea, and this behavior is dependent on a critical dopamine neuron. We tested the hypothesis that repeated cocaine exposure promotes learning and memory or attenuates the ability to extinguish the memory of respiratory behavior that relies on this dopaminergic neuron. Rotating disk electrode voltammetry revealed a K(m) and V(max) of dopamine uptake in snail brain of 0.9 micromol l(-1) and 558 pmol s(-1) g(-1) respectively, and the IC(50) of cocaine for dopamine was approximately 0.03 micromol l(-1). For operant conditioning, snails were given 5 days of 1 h day(-1) immersion in water (control) or 0.1 micromol l(-1) cocaine, which was the lowest dose that maximally inhibited dopamine uptake, and snails were trained 3 days later. No changes were found between the two groups for learning or memory of the operant behavior. However, snails treated with 0.1 micromol l(-1) cocaine demonstrated impairment of extinction memory during reinstatement of the behavior compared with controls. Our findings suggest that repeated exposure to cocaine modifies the interaction between the original memory trace and active inhibition of this trace through extinction training. An understanding of these basic processes in a simple model system may have important implications for treatment strategies in cocaine addiction.

Animals↗
PubMed2002

The effects of continuous versus partial reinforcement schedules on associative learning, memory and extinction in Lymnaea stagnalis.

A continuous schedule of reinforcement (CR) in an operant conditioning procedure results in the acquisition of associative learning and the formation of long-term memory. A 50 % partial reinforcement (PR) schedule does not result in learning. The sequence of PR-CR training has different and significant effects on memory retention and resistance to extinction. A CR/PR schedule results in a longer-lasting memory than a PR/CR schedule. Moreover, the memory produced by the CR/PR schedule is resistant to extinction training. In contrast, extinction occurs following the PR/CR schedule.

Animals↗
PubMed2006

Concomitant deficits in working memory and fear extinction are functionally dissociated from reduced anxiety in metabotropic glutamate receptor 7-deficient mice.

Metabotropic glutamate receptor 7 (mGluR7), a receptor with a distinct brain distribution and a putative role in anxiety, emotional responding, and spatial working memory, could be an interesting therapeutic target for fear and anxiety disorders. mGluR7-deficient (mGluR7-/-) mice showed essentially normal performance in tests for neuromotor and exploratory activity and passive avoidance learning but prominent anxiolytic behavior in two anxiety tests. They showed a delayed learning curve during the acquisition of the hidden-platform water maze, and three interspersed probe trials indicated that mGluR7-/- mice were slower to acquire spatial information. Working memory in the water maze task and the radial arm maze was impaired in mGluR7-/- mice compared with mGluR7+/+. mGluR7-/- mice also displayed a higher resistance to extinction of fear-elicited response suppression in a conditioned emotional response protocol. In a non-fear-based water maze protocol, mGluR7-/- mice displayed similar delayed extinction. These observed behavioral changes are probably not attributable to changes in AMPA or NMDA receptor function because expression levels of AMPA and NMDA receptors were unaltered. Extinction of conditioned fear is an active and context-dependent form of inhibitory learning and an experimental model for therapeutic fear reduction. It appears to depend on glutamatergic and higher-level brain functions similar to those involved in spatial working memory but functionally dissociated from those that mediate constitutional responses in anxiety tests.

Analysis of Variance↗
PubMed2005

Regulation of gephyrin and GABAA receptor binding within the amygdala after fear acquisition and extinction.

Both the acquisition and extinction of conditioned fear appear to require the basolateral amygdala (BLA). Because these two forms of learning have opposing effects on the expression of conditioned fear, we hypothesized that they may modulate GABAergic tone differentially within the BLA. Previously, we reported that gene expression for the GABA(A) receptor clustering protein gephyrin was significantly downregulated in the BLA after fear acquisition (Ressler et al., 2002). Here we demonstrate an analogous decrease in BLA gephyrin protein levels, together with a decrease in the surface expression of GABA(A) receptors in the BLA after fear acquisition, as evidenced by decreased binding of H3-flunitrazepam. In marked contrast, gephyrin mRNA and protein levels in the BLA significantly increased after extinction training, as did H3-flunitrazepam binding. These results implicate the protein gephyrin in both fear acquisition and extinction and suggest that the modulation of gephyrin and GABA(A) receptor expression in the BLA may play a role in the experience-dependent plasticity underlying both of these types of learning. Furthermore, these results demonstrate that physiologically relevant, dynamic alterations of GABAergic synapses occur during the consolidation phase of BLA-dependent learning and may interact with previously described alterations in glutamatergic transmission to initiate and stabilize memory formation in vivo.

Amygdala↗