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Interactions between homogeneous conditioned motor reflexes during conditioned reflex switching: transfer of learning and interference.

Studies in rabbits of the time course of the formation of conditioned reflex switching of homogeneous reflexes showed that learning involved three main stages, characterized by the extent of stability of the conditioned reflexes, their interaction, and the level of switching. Formation of conditioned reflex switching was found to involve transfer of motor learning and interference of motor reflexes.

Animals↗

A way to install conditioned modulation in the Rescorla-Wagner axiom: the amplifier model of Pavlovian conditioning (AMP).

Although the Rescorla-Wagner axiom has been successful in explaining and predicting many phenomena in Pavlovian conditioning, it offers no explanation for the ability of stimuli to modulate conditioned responding to other stimuli (i.e., the occasion-setting effect). This article provides a mathematical model for Pavlovian conditioned modulation by adding simple rules to the Rescorla-Wagner axiom. In spite of its rudimentary stage, the proposed model can explain many of the basic findings of modulatory learning and suggests some new areas of research.

Animals↗

A rapid and sensitive method for measuring the conditional emotional response. II: On-the-baseline excitatory conditioning and extinction.

The present study outlines a rapid and sensitive on-the-baseline conditional emotional response (CER) procedure. Using rats as the experimental subject, the method detects delay conditioning, incubation, extinction and spontaneous recovery. In addition, the method detects conditional responding using electric shock ranging from 0.23 to 0.50 mA as the unconditional stimulus. Because of its speed and sensitivity, the method shelters the subject from unnecessary long-term deprivation and pain.

Animals↗

Language conditioning, emotional instructions, and cognitions in conditioned responses to fear-relevant and fear-irrelevant stimuli.

This study compared the effects of experimentally induced self-verbalizations (SV) on conditioned responses to fear-relevant (snakes) and fear-irrelevant (rabbits) stimuli. To extend the analysis of "preparedness theory" beyond its former reliance on physiological measures of fear, subjective and behavioral measures were also included. Using aversive tones (UCS) and slides of snakes or rabbits (CS), fear was classically conditioned in 44 volunteers. In 20 subsequent language conditioning trials without aversive tones, the same slides were paired with verbalizations referring either to positive features of the animals (stimulus-referent SV) or to approach behavior (response-referent SV). Skin conductance responses to fear-relevant stimuli were more readily acquired, of higher magnitude, and more resistant to extinction. Extinction was differentially affected by the two types of SV. Snakes were consistently evaluated more negatively than rabbits and approached less in a behavior test. Results are discussed in relation to preparedness theory and interpreted within Staats' social-behavioral learning paradigm.

Adolescent↗

Effects of conditioned stimulus preexposure on human electrodermal conditioning.

Two experiments investigated the effects of conditioned stimulus (CS) preexposure on Pavlovian differential conditioning and extinction of the skin conductance response. In both experiments, half the subjects were exposed to 20 presentations each of the CS+ and CS-, and the other half were exposed to control stimuli. CS duration was 8 sec. The unconditioned stimulus in Experiment 1 (N = 48) was a 1000 Hz tone of 80 dB which signalled a reaction time requirement, and in Experiment 2 (N = 48), it was a 1 sec burst of white noise at 105 dB. The results of Experiment 1 indicated that no-preexposure groups displayed more CS+/CS- differentiation than preexposure groups during acquisition and more resistance to extinction, at least for the first interval anticipatory response. In addition, the results of Experiment 2 indicated that no-preexposure groups displayed more differentiation than preexposure groups in terms of the second interval anticipatory response. These data constitute a demonstration of the latent inhibition effect with human subjects, and imply that there is an intrinsic relationship between the orienting response and the conditioning process.

Acoustic Stimulation↗

Parasagittal thalamic knife cuts retard Pavlovian eyeblink conditioning and abolish the tachycardiac component of the heart rate conditioned response.

Rabbits received parasagittal knife cuts lateral to the mediodorsal nucleus of the thalamus (MD), severing afferents and efferents to and from the prefrontal cortex. These animals were compared to sham animals in a Pavlovian eyeblink and heart rate conditioning experiment in which a tone was the conditioned stimulus (CS) and paraorbital electrical shock was the unconditioned stimulus (US). Knife cuts retarded acquisition of the eyeblink conditioned response (CR), and abolished the late-occurring tachycardiac component of the heart rate CR. These data are compatible with previous experiments which suggest that MD participates in the sympathetic control associated with somatomotor learning.

Animals↗

Reduced-intensity conditioning allogeneic blood stem cell transplantation with fludarabine and oral busulfan with or without pharmacokinetically targeted busulfan dosing in patients with myeloid leukemia ineligible for conventional conditioning.

We prospectively compared outcomes after a fludarabine (Flu) plus oral busulfan (Bu)-containing reduced-intensity conditioning regimen (150 mg/m2 Flu and 10 mg/kg oral Bu), with (n = 32; Flu- T Bu group) or without (n = 30; Flu-Bu group) therapeutic dose monitoring and dose adjustment of Bu. All patients received peripheral blood stem cells from a genoidentical sibling, and study cohorts had similar patient characteristics. Dose adjustments of Bu were required in 20 (63%) patients in the Flu- T Bu group (median final dose, 8.89 mg/kg; range, 6.3-13.34 mg/kg). Donor T-cell and granulocyte engraftments were similar, and early conditioning-related toxicities were mild and similar in both study groups. With a median follow-up of 45 months (51 months in the 37 survivors), posttransplantation outcomes did not differ between cohorts. The strongest predictor of 2-year overall survival and leukemia-free survival was the presence of chronic graft-versus-host disease (77% versus 34% for overall survival and 74% versus 34% for leukemia-free survival; P < .001 for both outcomes). In conclusion, therapeutic dose monitoring of oral Bu in a reduced-intensity conditioning setting does not seem to affect outcome, although further studies may identify very-high-risk patients who benefit from this strategy.

Administration, Oral↗

Combat veterans show normal discrimination during differential trace eyeblink conditioning, but increased responsivity to the conditioned and unconditioned stimulus.

The question addressed in the present study was whether post-traumatic stress disorder (PTSD) results in associative learning impairments. To answer this question, differential trace eyeblink (EB) conditioning was studied in combat veterans with PTSD, combat veterans without PTSD, and non-combat veterans without PTSD. Veterans with PTSD showed normal EB discrimination, suggesting that associative learning is not impaired by PTSD. Veterans with PTSD also showed normal extinction. However, subjects with PTSD showed more EB conditioned responses (CRs), as well as increased CR amplitude. Increased response amplitude to the airpuff unconditioned stimulus presented alone (viz. the unconditioned response), as well as to the airpuff on CS+ trials during conditioning also occurred in the subjects with PTSD. These findings suggest increased reactivity in combat veterans with PTSD, compared to those without PTSD, but such heightened reactivity does not affect somatomotor associative learning.

Acoustic Stimulation↗

Memory after frontal/temporal disconnection in monkeys: conditional and non-conditional tasks, unilateral and bilateral frontal lesions.

Seven Cynomolgus monkeys (Macaca fascicularis) learned a series of reward-visual conditional discrimination problems, in which the arrival or non-arrival of a food pellet at the beginning of each trial acted as an instruction cue, signalling which of two visually distinct stimulus objects the animal should choose on that trial in order to obtain a further food pellet reward. Following surgical removal of the ventrolateral prefrontal cortex in one hemisphere and the inferior temporal cortex in the contralateral hemisphere, combined with forebrain commissurotomy, the four operated animals were severely impaired at relearning this task. They were not impaired, however, in non-conditional visual discrimination learning. Extending the unilateral frontal lesion to include the ventromedial prefrontal cortex had no detrimental effect, nor did complete unilateral removal of the frontal cortex. In a third experiment, the operated animals underwent a further surgery to remove either ventrolateral, ventral or complete frontal cortex similar to that in the opposite hemisphere. Compared to their previous level of performance, the animals with bilateral ventrolateral prefrontal lesions were now mildly impaired and the animals with the bilateral lesion extended to the ventromedial cortex more severely impaired on the non-conditional visual discrimination task. The bilaterally lobectomized animals were unable to relearn the task. We suggest that behaviour in visual learning tasks is controlled by cortical convergence upon subcortical structures, possibly by striatal efferents from both the visual cortex and frontal cortex, and that intrahemispheric convergence of these two efferents within the corpus striatum of one hemisphere could allow detailed control of visual choices by non-visual information, while subcortical interhemispheric transfer allows only less detailed, more general control.

Animals↗

5-HT3 receptor antagonist, tropisetron, does not influence ethanol-induced conditioned taste aversion and conditioned place aversion.

Numerous works have demonstrated an interaction between 5-HT3 receptor antagonists and some of the effects of ethanol (EtOH) using biochemical, electrophysiological, and behavioral techniques. Thus 5-HT3 antagonists are capable of reducing EtOH-induced release of dopamine in the nucleus accumbens, EtOH-induced hyperlocomotion, and voluntary EtOH consumption in laboratory animals. In addition to its rewarding effect, EtOH possesses aversive properties as demonstrated in the conditioned taste aversion (CTA) and conditioned place aversion (CPA) paradigms. The role of 5-HT3 receptors in aversive effects of EtOH remains, however, unknown. We decided to study the effect of 5-HT3 antagonist, tropisetron, on aversive properties of EtOH (1.5 g/kg i.p.) in rats using the CTA and CPA models. In addition, effect of tropisetron on morphine (Mf)-induced CTA (10.0 mg/kg SC) was investigated. Tropisetron (0.001-0.5 mg/kg) did not influence CTA produced by EtOH and Mf. When given alone, it failed to produce any taste conditioning. Furthermore, tropisetron did not modify CPA induced by EtOH. Our results suggest that 5-HT3 receptors are not involved in aversive effects of acute doses of EtOH.

Animals↗

Hippocampal place cells acquire location-specific responses to the conditioned stimulus during auditory fear conditioning.

We recorded neurons from the hippocampus of freely behaving rats during an auditory fear conditioning task. Rats received either paired or unpaired presentations of an auditory conditioned stimulus (CS) and an electric shock unconditioned stimulus (US). Hippocampal neurons (place and theta cells) acquired responses to the auditory CS in the paired but not in the unpaired group. After CS-US pairing, rhythmic firing of theta cells became synchronized to the onset of the CS. Conditioned responses of place cells were gated by their location-specific firing, so that after CS-US pairing, place cells responded to the CS only when the rat was within the cell's place field. These findings may help to elucidate how the hippocampus contributes to context-specific memory formation during associative learning.

Acoustic Stimulation↗

Resistance to extinction of conditioned odor perceptions: evaluative conditioning is not unique.

A tasteless odor will smell sweeter after being sampled by mouth with sucrose and will smell sourer after being sampled with citric acid. This tasty-smell effect was found in experiments that compared odor-taste and color-taste pairings. Using odors and colors with minimal taste (Experiment 1), the authors found that repeated experience of odor-taste mixtures produced conditioned changes in odor qualities that were unaffected by intermixed color-taste trials (Experiment 2). An extinction procedure, consisting of postconditioning presentations of the odor in water, had no detectable effect on the changed perception of an odor (Experiments 3 and 4). In contrast, this procedure altered judgments about the expected taste of colored solutions. Evaluative conditioning (conditioned changes in liking) is claimed to be resistant to extinction. However, these results suggest that resistance to extinction in odors is related to the way they are encoded rather than to their hedonic properties.

Adult↗

Ibotenate lesions of the hippocampus enhance latent inhibition in conditioned taste aversion and increase resistance to extinction in conditioned taste preference.

In 2 experiments, the effects of axon-sparing lesions of the hippocampus on performance in aversive and appetitive taste conditioning tasks were investigated. In Experiment 1, hippocampally lesioned rats showed no impairment of conditioned taste aversion learning relative to control subjects, but they did display an increased sensitivity to latent inhibition (LI). In Experiment 2, the same hippocampectomized rats acquired a conditioned taste preference but failed to show any evidence of extinction. The influence of the neurotoxic lesion on LI is in the opposite direction to the effect typically found following hippocampal damage induced by traditional methods. Accordingly, the data present challenges for most current theories of hippocampal function.

Animals↗

Trace eyeblink conditioning in the freely moving rat: optimizing the conditioning parameters.

Trace eyeblink conditioning (EBC) parameters, with an airpuff unconditioned stimulus, were examined in male Fischer 344 X Brown Norway F1 rats. Integrated electromyographic activity from the upper eyelid was recorded. An 8-kHz tone was superior to white noise as a conditioning stimulus. Rats trained with 30 or 50 trials per session showed similar learning. Reversal of environmental lighting had no significant effect. Trace intervals of 0 and 250 ms yielded well-timed conditioned responses (CRs); intervals of 500 ms or more did not. These experiments provide parameters that reliably yield CRs and suggest limits on the temporal processing capabilities of the rat. EBC can thus be used as part of a comprehensive test battery for learning and memory in this species. Physiological recording and pharmacological manipulations may also be done easily. This combination of approaches should facilitate a more complete understanding of learning mechanisms and age-related memory impairments.

Animals↗

Classical conditioning of a flexor nerve response in spinal cats: effects of tibial nerve CS and a differential conditioning paradigm.

Previous studies have shown flexor nerve response increases produced by classical conditioning procedures in spinal cats when the conditioned stimulus (CS) was delivered to the superficial peroneal nerve and the unconditioned stimulus (US) was delivered to the ankle skin. In this study, these effects were produced when the CS was delivered to the whole tibial nerve or to the medial plantar branch. The finding that response increases followed by extinction effects could be obtained when either the superficial peroneal or the tibial nerve was utilized allowed the assessment of the effects of a differential conditioning paradigm. The responses to CS-US presentations on the superficial peroneal nerve increased, whereas responses to CS presentations on the tibial nerve remained unchanged. However, lack of extinction effects in the superficial peroneal data suggested that stimulation of the tibial nerve potentiated superficial peroneal evoked responses. Furthermore, responses evoked by stimulation of either nerve increased when paired trials were given on the tibial nerve. These data demonstrate that stimulation of the tibial nerve potentiates responses to superficial peroneal nerve stimulation but that superficial peroneal nerve stimulation has no effect on responses to CS presentations to the tibial nerve.

Animals↗

Lower incidence of Bronchiolitis obliterans in allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning compared with myeloablative conditioning.

Bronchiolitis obliterans (BO) is one of the most devastating complications after allogeneic stem cell transplantation (HSCT). However, its true pathogenesis is still to be elucidated. We conducted this study to find whether tissue damage due to high-dose chemo-radiotherapy is related to its pathogenesis. In all, 144 patients who received allogeneic HSCT between May 1999 and October 2001, and survived more than 80 days after transplant, were analyzed. Clinical course, pulmonary function tests, imaging studies including CT scan, and pathology results were reviewed. The overall incidence of BO was 9.7% (14/144). The cumulative incidence of BO at 2 years after transplant was 17% with myeloablative conditioning, and 2.3% with reduced intensity conditioning (P=0.024). Multivariate analysis showed that myeloablative conditioning was the only factor which affected the incidence of BO. Development of BO did not significantly affect the overall survival of patients. However, if they developed BO earlier than 200 days post transplant, the prognosis was significantly worse than if they developed it later than 200 days post transplant (P=0.003) or if they did not develop BO (P=0.002). Our results imply that tissue damage secondary to intensive chemo-radiotherapy may contribute to the pathogenesis of BO.

Adolescent↗

Vasopressin in the lateral septum promotes elemental conditioning to the detriment of contextual fear conditioning in mice.

Previous experiments using a classical fear conditioning paradigm have provided evidence that the processing of contextual conditional stimuli (CSs) by the hippocampus would be controlled by the amygdala through a modulation of hippocampal-lateral septal (H-LS) excitability. More specifically, our suggestion was that vasopressin release into the LS would occur in an elemental conditioning case [pairing CS-US (unconditional stimulus) procedure] and would result in less hippocampal-dependent contextual stimuli processing (i.e. overshadowing of CSs by the simple CS). Conversely, when an unpairing CS-US procedure is used, this would result in more contextual stimuli processing through a decrease in vasopressin release into the LS. The aim of the present experiment was to test this hypothesis using intraseptal injection of vasopressin or its V1/V2 antagonist. In agreement with this hypothesis, results suggest that vasopressin release into the LS would constitute a device by which priority is given to the more salient simple stimulus to the detriment of contextual information.

Acoustic Stimulation↗

Antibody response can be conditioned using electroacupuncture as conditioned stimulus.

To establish a new model of conditioned enhancement of antibody production, electroacupuncture was served as the conditioned stimulus (CS) and an injection of a protein antigen ovalbumin as the unconditioned stimulus (UCS). After a CS/UCS pairing was made, re-exposure of animals to the CS alone resulted in significant conditioned enhancement of anti-ovalbumin antibody production. Even in deep sleep induced by anesthesia, the animals can associate a single CS with UCS and an antibody response can be elicited upon subsequent re-exposure to CS in the absence of exogenous antigen. No effect of electroacupuncture on anti-ovalbumin antibody production was found.

Anesthesia↗