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Changes in hippocampal cholinergic activity following learning in mice.

A short bar-press operant conditioning acquisition session with food reward on continuous reinforcement was shown to induce a decrease (13.5%) of hippocampal choline acetyltransferase activity in mice. Such an effect seems to be specific to this kind of learning since no change was observed in several control groups, including a group of mice submitted to another type of conditioning in the same apparatus. It is suggested that these enzymatic modifications might be responsible for the delayed improvement of performance observed on retention of this task.

Acetylcholinesterase↗

Sensory reinforcement of head turning with nonambulatory, profoundly mentally retarded persons.

Two experiments examined the reinforcing value of response contingent sensory events consisting of combinations of visual, auditory, and vibratory stimulation. Ten nonambulatory, profoundly mentally retarded individuals participated in these studies. Four different stimulus combinations were required to achieve operant conditioning of head turning responses in 6 participants. These sensory reinforcers included 5-s simultaneous presentations of picture, music, and vibration (N = 2), picture and music (N = 2), picture and vibration (N = 1), and picture alone (N = 1). These results indicate that systematically varying a multimodal sensory event is a fruitful procedure for identifying positive reinforcers for nonambulatory, profoundly mentally retarded persons.

Adolescent↗

Neurochemical, but not behavioral, deviations in the offspring of rats following prenatal or paternal inhalation exposure to ethanol.

In addition to its widespread social use, ethanol is used extensively as an industrial solvent. Inhalation exposures to ethanol which produce narcosis in maternal rats are not teratogenic. The present study sought to extend the previous research by including offspring from paternal exposures, and testing for behavioral disorders in the offspring following maternal or paternal exposures. Groups of 18 male (approximately 450 g) and 15 female (200-300 g) Sprague-Dawley rats were exposed 7 hours/day for six weeks or throughout gestation to 16000, 10000, or 0 ppm ethanol by inhalation and then mated with untreated rats. Litters were culled to 4 males and 4 females, and were fostered within 16 hours after birth to untreated dams which had delivered their litters within 48 hours previously. Offspring from paternally or maternally exposed animals performed as well as controls on days 10-90 in tests of neuromotor coordination (ascent on a wire mesh screen, rotorod), activity levels (open field, modified-automated open field, and running wheel), and learning ability (avoidance conditioning and operant conditioning). In addition, brains of 10 21-day-old pups were analyzed for neurochemical differences from controls in concentrations of protein and the neurotransmitters acetylcholine, dopamine, norepinephrine, 5-hydroxytryptamine, substance P, Met-enkephalin, and beta-endorphin. Levels of acetylcholine, dopamine, substance P, and beta-endorphin were essentially unchanged in the offspring of rats exposed to ethanol. Complex, but significant changes in levels of norepinephrine occurred only in paternally exposed offspring. 5-Hydroxytryptamine levels were reduced in the cerebrum, and Met-enkephalin levels were increased in all brain regions of offspring from both maternally and paternally exposed rats.

Administration, Inhalation↗

Effects of multiple alcohol deprivations on operant ethanol self-administration by high-alcohol-drinking replicate rat lines.

Previously, we reported that the expression of an alcohol deprivation effect (ADE) under 24-h free-choice alcohol-drinking access in high-alcohol-drinking (HAD) replicate lines of rats is dependent upon repeated cycles of alcohol access and forced abstinence. In the present study, operant techniques (including progressive ratio measures) were used to examine the effects of initial deprivation length and number of deprivation cycles on the magnitude and duration of the ADE in HAD rats to test the hypothesis that repeated deprivations increase the reinforcing effects of ethanol. Adult male HAD-1 and HAD-2 rats were trained in two-lever operant chambers to concurrently self-administer 15% ethanol (v/v) on a fixed-ratio (FR)-5 schedule and water on an FR-1 schedule of reinforcement in daily 1-h sessions. Following 10 weeks of daily 1-h sessions, the HAD-1 and HAD-2 rats were randomly assigned to one of four groups (n=6-8/group/line): nondeprived, or deprived of alcohol for 2, 5, or 8 weeks. Following this initial period, the deprived groups were given 15% ethanol again in the operant chambers for a 2-week period, following which they were deprived again for 2 weeks (all three deprived groups). Following the fifth deprivation, the rats underwent a progressive ratio test to determine the breakpoints for the nondeprived and deprived groups. The expression of an ADE under operant conditions in HAD rats was dependent upon exposure to repeated cycles of ethanol access and abstinence. Additionally, repeated deprivations increased both the magnitude and the duration of the ADE as indicated by increased responding on the ethanol lever for more sessions. Breakpoint values for the deprived groups were 1.5-fold and twofold higher than the value for the nondeprived group for the HAD-1 and HAD-2 rats, respectively. The results suggest that repeated alcohol deprivations increased the expression of an ADE and the reinforcing effects of ethanol in both HAD replicate lines of rats, and these effects were more pronounced in the HAD-2 line than the HAD-1 line.

Alcohol Drinking↗

Reward-related neuronal activity in the rat superior colliculus.

The activity of single units in the intermediate and deep layers of the superior colliculus was recorded while rats performed an operant conditioning task. On all trials, each animal pressed a bar and then inserted his snout into a food cup; on half of the trials, food reinforcement was available. To test for tactile sensitivity, on half of the trials the rats received a puff of air to the face when the snout entered the food cup. Activity of most cells was correlated with the motor activity of inserting the snout into the food cup, even when reinforcement was not available. For many cells, a larger burst of activity was seen on the reinforced trials than on trials when rats made the same movements without the presence of reward. There was no evidence that an increase in tactile sensitivity occurred when the animal retrieved the reinforcement. These results suggest that cells in the superior colliculus have an increase in activity associated with reward retrieval, which for some neurons is not dependent on simple sensory or motor factors.

Action Potentials↗

How rats combine temporal cues.

The procedures for classical and operant conditioning, and for many timing procedures, involve the delivery of reinforcers that may be related to the time of previous reinforcers and responses, and to the time of onsets and terminations of stimuli. The behavior resulting from such procedures can be described as bouts of responding that occur in some pattern at some rate. A packet theory of timing and conditioning is described that accounts for such behavior under a wide range of procedures. Applications include the food searching by rats in Skinner boxes under conditions of fixed and random reinforcement, brief and sustained stimuli, and several response-food contingencies. The approach is used to describe how multiple cues from reinforcers and stimuli combine to determine the rate and pattern of response bouts.

Animals↗

Rationale and methodology for testing auditory cognition in songbirds.

Songbirds, and in particular zebra finches, present a wonderful opportunity to study cognition in species that have evolved specialized abilities and brain structures for auditory cognition. The authors describe the rationale, methods, and apparatus used to test the auditory perceptual and cognitive abilities of songbirds. They have developed an operant conditioning system for conducting discrimination experiments simultaneously with several songbirds. The system uses specialized single-board computers, standard personal computers, CD-ROMs, and custom-written software to present stimuli, control training, and record responses. Also, the authors describe software to produce high-quality synthesized and naturally occurring acoustic stimuli for use in studies of auditory cognition. Typical results from a challenging frequency-range discrimination are included.

Acoustic Stimulation↗

Within-session repeated acquisition behavior in rats as a potential model of executive function.

Higher levels of cognition, such as executive functions, are known to be disrupted in psychiatric disorders such as schizophrenia. As a potential model of executive function, rats were trained in a three-lever operant conditioning chamber to respond on two of the three levers in one of six possible correct sequences. When the rat completed a two-response sequence correctly for 10 consecutive trials, the correct sequence was randomly changed to another two-response sequence without signaling the rat. Rats readily acquired the behavioral baseline and completed all six response-sequences within a 60-min session. Phencyclidine, MK-801 ((5S,10R)-(+)-5-Methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine), apomorphine, scopolamine and triazolam all produced dose-related decreases in the total number of sequences completed. Phencyclidine and MK-801 markedly increased all errors while scopolamine produced modest increases; triazolam increased only total and intrarule errors, while apomorphine had no significant effect on errors. The present results suggest that within-session repeated acquisition of response sequences has the potential to be a useful model for studying executive function in rats.

Animals↗

Cannabinoid CB1 receptor is dispensable for memory extinction in an appetitively-motivated learning task.

The interaction of the cannabinoid CB1 receptor with its endogenous ligands plays an essential role in extinction of aversive memories (Marsicano, G., Wotjak, C.T., Azad, S.C., Bisogno, T., Rammes, G., Cascio, M.G., Hermann, H., Tang, J., Hofmann, C., Zieglgansberger, W., Di, M., V, Lutz, B., 2002. The endogenous cannabinoid system controls extinction of aversive memories. Nature 418, 530-534). The present study tested the generality of this observation in respect to positively-reinforced memories. To this end, male cannabinoid CB1 receptor deficient mice (CB1R-/-) and their wild-type littermate controls (CB1R+/+) were trained in an appetitively-motivated operant conditioning task, in which food-deprived animals received a food reward on nose-poking into an illuminated hole. During training, CB1R-/- turned out to be less motivated to participate in the task. After further restriction of daily food consumption, however, CB1R-/- reached the same level of performance as CB1R+/+ as far as number of correct responses and errors of omission are concerned. The accuracy of performance served as a measure for the memory of the light-reward association and was stable at similarly high levels over a retention period of 9 days without additional training (97.6+/-0.5% vs. 97.0+/-0.9% correct responses). During subsequent extinction training, the positive reinforcement was omitted. As a consequence, both CB1R-/- and CB1R+/+ showed a similar decline in accuracy of performance and total number of correct responses, accompanied by an increase in errors of omission. These data demonstrate that the cannabinoid CB1 receptor is not essential for extinction of the stimulus-response association in an appetitively-motivated learning task.

Animals↗

The relation between social behavior and negative affect in psychosis-prone individuals: an experience sampling investigation.

Daily social behavior and negative affect were examined in a sample of individuals with a wide spectrum of psychosis-proneness scores. Using the experience sampling method, participants were signaled five times per day for a 1-week period to provide naturalistic reports of location, activity, and social behavior. Little evidence was found for a direct association between psychosis-proneness and specific behavioral profiles, but individuals with higher scores of psychosis-proneness reported spending more time doing nothing or waiting. However, the levels of anxious and depressed moods experienced in certain social and environmental contexts were also predicted by psychosis-proneness scores. The present results indicate that psychosis-proneness was associated with an increase in anxiety when individuals were with friends and an increase in depressed mood in daily task situations such as working or studying. By contrast, psychosis-proneness predicted a decrease in depressed and anxious moods in other situations when the individual was not likely to be confronted by social contact with less known individuals, and lower anxious and depressed moods when in secure environments (in one's own home, home of family or friends). The implications of these findings are discussed in terms of understanding the expression of psychosis vulnerability and the potential reinforcement of maladaptive social behavior through operant conditioning mechanisms.

Affect↗

Impulsive-like behavior in differential-reinforcement-of-low-rate 36 s responding in mice depends on training history.

Prior behavioral history in operant conditioning paradigms may induce impulsive-like responding as shown in rats. Little is known to what extent behavioral history influences subsequent behavior in mice, therefore the present study investigated the effects of lever-pressing under a fixed-ratio 5 schedule of reinforcement on subsequent differential-reinforcement-of-low-rate (DRL) 36 s performance in wild type mice compared to the behavior of 5-HT1B receptor knockout mice. Acquisition of both autoshaping and fixed-ratio 5 training was faster in 5-HT1B receptor knockout compared to wild type mice. Nevertheless, in the DRL 36 s procedure no differences were observed between genotypes. Both wild type and 5-HT1B receptor knockout mice displayed premature or impulsive-like responding in the DRL 36 s procedure, for example a peak location of responses around 20 s and high rates of responding. Taken together, the present data suggest that impulsive-like responding in the DRL 36 s procedure in mice depends on prior behavioral history.

Animals↗

Maintaining accuracy at the expense of speed: stimulus similarity defines odor discrimination time in mice.

Odor discrimination times and their dependence on stimulus similarity were evaluated to test temporal and spatial models of odor representation in mice. In a go/no-go operant conditioning paradigm, discrimination accuracy and time were determined for simple monomolecular odors and binary mixtures of odors. Mice discriminated simple odors with an accuracy exceeding 95%. Binary mixtures evoking highly overlapping spatiotemporal patterns of activity in the olfactory bulb were discriminated equally well. However, while discriminating simple odors in less than 200 ms, mice required 70-100 ms more time to discriminate highly similar binary mixtures. We conclude that odor discrimination in mice is fast and stimulus dependent. Thus, the underlying neuronal mechanisms act on a fast timescale, requiring only a brief epoch of odor-specific spatiotemporal representations to achieve rapid discrimination of dissimilar odors. The fine discrimination of highly similar stimuli, however, requires temporal integration of activity, suggesting a tradeoff between accuracy and speed.

Animals↗

Extinction of cocaine self-administration reveals functionally and temporally distinct dopaminergic signals in the nucleus accumbens.

While Pavlovian and operant conditioning influence drug-seeking behavior, the role of rapid dopamine signaling in modulating these processes is unknown. During self-administration of cocaine, two dopaminergic signals, measured with 100 ms resolution, occurred immediately before and after the lever press (termed pre- and post-response dopamine transients). Extinction of self-administration revealed that these two signals were functionally distinct. Pre-response transients, which could reflect the motivation to obtain the drug, did not decline during extinction. Remarkably, post-response dopamine transients attenuated as extinction progressed, suggesting that they encode the learned association between environmental cues and cocaine. A third type of dopamine transient, not time locked to overt stimuli, decreased in frequency during extinction and correlated with calculated cocaine concentrations. These results show that dopamine release transients involved in different aspects of cocaine self-administration are highly plastic--differentially governed by motivation, learned associations linked with environmental stimuli, and the pharmacological actions of cocaine.

Analysis of Variance↗

Stressful stimuli modulate memory formation in Lymnaea stagnalis.

Stress has been shown to be a strong modulator of learning and memory in animals. We employ operant training of aerial respiratory behaviour in our model system, the pond snail Lymnaea stagnalis, to show that application of an acute consistent physical stressor enhances memory formation. A single 30 min operant conditioning training session, which normally results in intermediate-term memory (ITM) persisting 3h, results in long-term memory (LTM) persisting 24h if immediately preceded or followed by a stressor, for example a 30s exposure to 25 mM KCl. Other physical stressors (0.3% quinine-HCl or quick cooling and warming) similarly enhance memory formation. The memory is context specific and is not seen after the application of too much or too little stress. The memory can be extinguished by exposing snails to the hypoxic training environment and withholding reinforcing stimuli. The LTM that results from 30 min of training and stressor exposure is dependent on de novo protein synthesis and gene transcription in a single neuron, RPeD1. Because the soma of RPeD1 must be present for memory augmentation by the application of a stressor we are well placed for future investigations to directly determine the specific molecular alterations by which stress primes the formation of LTM.

Adaptation, Physiological↗

Odor discrimination assessment with an automated olfactometric method in a prosimian primate, Microcebus murinus.

The present study was aimed at adapting an automated olfactometer designed for use with rodents to a nocturnal lemur Microcebus murinus. This apparatus allows rigorous control of odor stimuli. We show that M. murinus could remain quiet and attentive for about 20 min in the test chamber, allowing daily sessions of 40 consecutive trials. This allowed us to train M. murinus subjects to learn a go/no-go discrimination procedure using fruity-odor cues. Each of seven subjects reached or exceeded a criterion of 33 correct responses in a block of 40 trials in a range of 4-14 training sessions. When trained on an odor reversal task, performance initially dropped sharply, followed by rapid acquisition of the new task. These outcomes demonstrate that, like rodents, M. murinus can be trained using operant conditioning in an automated olfactometer. This species should prove useful for investigating cognitive capacities and neurodegenerative disease in a primitive primate model.

Animals↗

The token economy for schizophrenia: review of the literature and recommendations for future research.

The token economy is a treatment intervention based on principles of operant conditioning and social learning. Developed in the 1950s and 1960s for long-stay hospital patients, the token economy has fallen out of favor since that time. The current review was undertaken as part of the 2003 update of the schizophrenia treatment recommendations of the Patient Outcomes Research Team (PORT). A total of 13 controlled studies of the token economy were reviewed. As a group, the studies provide evidence of the token economy's effectiveness in increasing the adaptive behaviors of patients with schizophrenia. Most of the studies are limited, however, by methodological shortcomings and by the historical context in which they were performed. More research is needed to determine the specific benefits of the token economy when administered in combination with contemporary psychosocial and psychopharmacological treatments.

Behavior Therapy↗

Detection of contour continuity and closure in three-month-olds.

The present study used an operant conditioning procedure and contour integration stimuli to test three-month-olds' sensitivity to both contour continuity and contour closure. The data demonstrate an immaturity of continuity detection and a lack of closure detection at that age, relative to a previous finding of a heightened sensitivity to closed contours in adult observers. This finding modifies the general view of infant visual perception that has been more focused on the quantitative development of various aspects of visual perception, including contrast sensitivity, binocular disparity processing, perceptual completion, and other perceptual skills. These results suggest qualitative change in terms of the organization of visual information during development, and implications of this finding for visual maturation of mechanisms suggested to underlie these detection abilities are discussed.

Conditioning, Operant↗

Effects of operational parameters on cake formation of CaSO4 in nanofiltration.

Inorganic fouling is one of the major limitations of nanofiltration (NF) application in drinking water treatment. In this study, we report the effect of operating parameters on the fouling of NF membranes by CaSO4 in terms of cake growth at membrane surface under various operating conditions. Increasing operating pressure and decreasing crossflow velocity promote CaSO4 nucleation and crystallization, thus enhance membrane fouling. The flux decline and its dynamics due to the change of operating parameters are assessed quantitatively based on a resistance model. Applied filtration pressure is found to have the most dominant impact on the inorganic fouling. It is shown that the filtration resistance caused by the formation and growth of CaSO4 cake on membrane surface is dependent on operating parameters.

Calcium Sulfate↗