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Operant conditioning after temporal lobe lesions in man: conditional and simple discrimination learning.

Temporal lobe lesions have been found to impair the acquisition of classical conditional discrimination learning in an eyelid conditioning paradigm, with sparing of simple eyelid conditioning. In the present study, subjects with left or right temporal resections were compared with normal controls on two operant conditioning tasks using a conditional and a simple discrimination paradigm analogous to the previously reported classical conditioning tasks. Subjects with right temporal lesions, and to a lesser extent those with left temporal lesions, were impaired relative to frontal lobe and control subjects in the acquisition of a conditional discrimination within an operant conditioning setting. A subsequent experiment showed that both left and right temporal lobe subjects were unimpaired on a simple operant discrimination task. These findings are compatible with theory relating hippocampal function to the learning of if-then rules.

Adult↗

Interaction of haloperidol and area postrema lesions in the disruption of amphetamine-induced conditioned taste aversion learning in rats.

Two experiments were run to determine the mechanisms underlying the acquisition of an amphetamine-induced conditioned taste aversion. In the first experiment, it was shown that pretreatment with haloperidol (0.1-0.5 mg/kg, IP) attenuated. but did not prevent, taste aversion learning produced by amphetamine (3 mg/kg, IP). In the second experiment, combining area postrema lesions with haloperidol (0.5 mg/kg) pretreatment completely blocked the acquisition of an amphetamine-induced taste aversion. The results are interpreted as indicating that amphetamine-induced taste aversion learning has both a central component, which is mediated by dopaminergic receptors, and a nondopaminergic peripheral component, which is mediated by the area postrema.

Amphetamine↗

Impaired conditioned taste aversion learning in spinophilin knockout mice.

Plasticity in dendritic spines may underlie learning and memory. Spinophilin, a protein enriched in dendritic spines, has the properties of a scaffolding protein and is believed to regulate actin cytoskeletal dynamics affecting dendritic spine morphology. It also binds protein phosphatase-1 (PP-1), an enzyme that regulates dendritic spine physiology. In this study, we tested the role of spinophilin in conditioned taste aversion learning (CTA) using transgenic spinophilin knockout mice. CTA is a form of associative learning in which an animal rejects a food that has been paired previously with a toxic effect (e.g., a sucrose solution paired with a malaise-inducing injection of lithium chloride). Acquisition and extinction of CTA was tested in spinophilin knockout and wild-type mice using taste solutions (sucrose or sodium chloride) or flavors (Kool-Aid) paired with moderate or high doses of LiCl (0.15 M, 20 or 40 mL/kg). When sucrose or NaCl solutions were paired with a moderate dose of LiCl, spinophilin knockout mice were unable to learn a CTA. At the higher dose, knockout mice acquired a CTA but extinguished more rapidly than wild-type mice. A more salient flavor stimulus (taste plus odor) revealed similar CTA learning at both doses of LiCl in both knockouts and wild types. Sensory processing in the knockouts appeared normal because knockout mice and wild-type mice expressed identical unconditioned taste preferences in two-bottle tests, and identical lying-on-belly responses to acute LiCl. We conclude that spinophilin is a candidate molecule required for normal CTA learning.

Animals↗

Associative learning in humans--conditioning of sensory-evoked brain activity.

A classical conditioning paradigm was employed in two experiments performed on 35 human volunteers. In nine subjects, the presentation of Landolt rings (conditioned stimuli, CS + ) was paired with an electric stimulus (unconditioned stimuli, UCS) applied to the left median nerve. Neutral visual control stimuli were full circles (CS -) that were not paired with the UCS. The skin conductance response (SCR) was determined in a time interval of 5 s after onset of the visual stimuli, and it was measured in the acquisition and test phase. Associative learning was reflected by a SCR occurring selectively with CS +. The same experiment was repeated with another group of 26 adults while electroencephalogram (EEG) was recorded from 30 electrodes. For each subject, mean evoked potentials were computed. In 13 of the subjects, a conditioning paradigm was followed while the other subjects served as the control group (non-contingent stimulation). There were somatosensory and visual brain activity evoked by the stimuli. Conditioned components were identified by computing cross-correlation between evoked somatosensory components and the averaged EEG. In the visual evoked brain activity, three components with mean latencies of 105.4, 183.2, and 360.3 ms were analyzed. Somatosensory stimuli were followed by major components that occurred at mean latencies of 48.8, 132.5, 219.7, 294.8, and 374.2 ms latency after the shock. All components were analyzed in terms of latency, field strength, and topographic characteristics, and were compared between groups and experimental conditions. Both visual and somatosensory brain activity was significantly affected by classical conditioning. Our data illustrate how associative learning affects the topography of brain electrical activity elicited by presentation of conditioned visual stimuli.

Adult↗

Conditioned taste aversion as a learning and memory paradigm.

Conditioned taste aversion (CTA) is a well established learning and memory paradigm in rats and mice that is considered to be a special form of classical conditioning. Rodents--as well as many other species including man--learn to associate a novel taste (CS) with nausea (US), and as a consequence avoid drinking fluid with this specific taste. In contrast to other types of classical conditioning, even CS-US intervals lasting several hours lead to an aversion to the gustatory CS. With increasing CS-US delay duration, however, the aversion against the CS gradually decreases. Mice differ from rats in their reaction to the CS as well as the US. They tolerate a much higher concentration of saccharin and they do not show any clear signs of nausea when injected with the US. Advantages of this task are its relative independence of motor behavior, well described pathways for the CS and partly the US, and the wealth of available anatomical and pharmacological data implying several brain structures (e.g. parabrachial nucleus, amygdala, insular cortex), neurotransmitters and their receptors (e.g. cholinergic system, NMDA-receptors), and cellular processes (e.g. expression of immediate early genes, Ras-MAP kinase signaling pathway, CREB phosphorilation, protein tyrosine phosphorilation, protein synthesis) in CTA. The CTA paradigm has also been successfully used to phenotype mouse mutants.

Animals↗

Perceptual or motor learning in SRT tasks with complex sequence structures.

We investigated under which conditions sequence learning in a serial reaction time task can be based on perceptual learning. A replication of the study of Mayr (1996) confirmed perceptual and motor learning when sequences were learned concurrently. However, between-participants manipulations of the motor and perceptual sequences only supported motor learning in cases of more complex deterministic and probabilistic sequence structures. Perceptual learning using a between-participants design could only be established with a simple deterministic sequence structure. The results seem to imply that perceptual learning can be facilitated by a concurrently learned motor sequence. Possibly, concurrent learning releases necessary attentional resources or induces a structured learning condition under which perceptual learning can take place. Alternatively, the underlying mechanism may rely on binding between the perceptual and motor sequences.

Adult↗

Effect of odor quality and intensity on conditioned odor aversion learning in the rat.

Odor quality and intensity were varied to test the ability of rats to associate odor with an induced illness. Rats were allowed 10 minutes access to water on each of nine days; deodorized air was directed towards each rat's nose while drinking at familiarization and recovery sessions (days 1-5 and 7-8, respectively) and odorized air at treatment and test sessions (days 6 and 9, respectively). Each rat was injected with LiCl following its drinking period on day 6. The difference between the amount of water consumed on day 6 and day 9 gave a measure of the conditioned aversion. Only mild or no aversion occurred with odors of n-butyric acid, benzylamine, cyclohexanone, and n-butanol. Strong conditioned aversions were obtained to odors of triethylamine, 1,4-cineole, and isoamyl acetate, and the degree of aversion increased linearly with the log of odor concentration. The effect of odor quality, intensity and presentation method, and the role of the different chemoreceptor systems in the acquisition of odor aversions are discussed.

Animals↗

Lidocaine infusion in a critical region of cerebellum completely prevents learning of the conditioned eyeblink response.

New Zealand white rabbits were implanted with cannulas in the dorsal or ventral aspect of the anterior interpositus nucleus. Three days (and 6 days for some dorsal-infusion animals) of standard tone-airpuff training was given with continuous infusion (constant rate of 0.2 microL/min) of lidocaine or saline. All animals were then given 3 days of training with no infusion. All lidocaine-infused animals exhibited no conditioned responses in the 3 or 6 days of infusion training. Dorsal-infusion animals learned in the subsequent 3 days of no infusion training as if naive, that is, they exhibited no savings. Animals with ventral cannula locations learned during infusion training, as shown in postinfusion training. These results strongly support the hypothesis that the essential memory trace for eyeblink conditioning is formed and stored in the cerebellum.

Animals↗

[The effects of acute administration of thyrotropin-releasing hormone on conditioned active avoidance learning and passive avoidance learning in rats (author's transl)].

The effects of acute administration of thyrotropin-releasing hormone (TRH) on the fear motivated learning of male Wistar rats were studied using a shuttle box. Two kinds of experiments - active avoidance learning (shuttle avoidance learning) and passive avoidance learning were performed. TRH (500 microgram/kg) was injected subcutaneously 40 to 50 minutes before the test trials. 1. In shuttle avoidance learning, TRH facilitated the acquisition after 8 sessions-pretraining and retarded the extinction after 8 approximately 12 sessions-pretrainings compared with saline. In passive avoidance learning, however, the reverse results were obtained: TRH retarded the acquisition and facilitated the extinction. 2. In shuttle avoidance learning, the acquisition facilitating effect of TRH was seen only in poor performer rats (poor performer was defined as less than 37 median score of conditioned avoidance responses in 8 sessions-pretraining), but not in good performer rats (more than 37 conditioned avoidance responses). 3. In shuttle avoidance learning, the acquisition facilitating effect of TRH was not seen in poor performer rats after 15 sessions-pretrainings, and the extinction retarding effect of TRH was not seen in the rats after 28 sessions-pretrainings. 4. From the above results it can be concluded that TRH possesses a fear reducing effect, and the behavioral changes brought about by TRH are seen most obviously in the rats which are in highly fearful conditions.

Animals↗

Neural substrates of discriminative avoidance learning and classical eyeblink conditioning in rabbits: a double dissociation.

In a previous study, lesions of the deep cerebellar nuclei blocked classical eyeblink conditioning, but did not impair discriminative avoidance learning in rabbits. Here, was also found previously, lesions of the anterior and medial dorsal thalamic nuclei severely impaired discriminative avoidance learning. However, these lesions had no impact on discriminative eyeblink conditioning or reversal learning. These results complete the demonstration of a double dissociation, indicating distinct neural substrates for the acquisition of these learned behaviors. It is proposed that the two learning circuits identified by these studies mediate, respectively, acquisition of specific adaptive reflexes and whole-body, voluntary goal-directed movements.

Animals↗

Appetitive learning using visual conditioned stimuli in the pond snail, lymnaea.

Feeding can be conditioned in the pond snail Lymnaea stagnalis to two different visual stimuli (a black panel or a 5-mm black and white check surround) by pairing the potential conditioned stimulus (CS) with sucrose. Exclusion of chemical cues (associated with differences between the water in home tank and that in training apparatus) that could serve as CS is important for successful visual conditioning. A featureless gray surround, used as an alternative to the check (to which it was matched in luminance) in counterbalanced training designs, was discriminated from the check, showing that resolution (for which the eyes would be necessary) was occurring. The gray surround was largely ineffective as a CS. Single-trial learning was possible with the black panel, but not with the check; it is argued that this may be due to lack of prior experience of stimuli like the check. Conditioning of feeding has now been obtained in Lymnaea to chemical, tactile, and visual cues, opening the way to comparative studies of the neural circuitry underlying appetitive conditioning in different senses, so far explored in Lymnaea only for tactile CS. Such comparative studies are as yet largely lacking in invertebrates.

Animals↗

Deficits on conditional associative-learning tasks after frontal- and temporal-lobe lesions in man.

Patients with unilateral frontal- or temporal-lobe excisions were tested on a spatial and a nonspatial conditional associative task. These tasks required the learning of arbitrary associations between a set of stimuli and a set of responses. Patients with excisions from the left or right frontal cortex were severely impaired in learning both tasks. Patients with left or right temporal-lobe excisions that did not involve extensive damage to the hippocampal region were not impaired, whilst those with more radical involvement of the hippocampal region exhibited deficits that were material-specific and varied with the side of the lesion.

Adolescent↗

Blockade of NMDA receptors in the dorsomedial striatum prevents action-outcome learning in instrumental conditioning.

Although there is consensus that instrumental conditioning depends on the encoding of action-outcome associations, it is not known where this learning process is localized in the brain. Recent research suggests that the posterior dorsomedial striatum (pDMS) may be the critical locus of these associations. We tested this hypothesis by examining the contribution of N-methyl-D-aspartate receptors (NMDARs) in the pDMS to action-outcome learning. Rats with bilateral cannulae in the pDMS were first trained to perform two actions (left and right lever presses), for sucrose solution. After the pre-training phase, they were given an infusion of the NMDA antagonist 2-amino-5-phosphonopentanoic acid (APV, 1 mg/mL) or artificial cerebral spinal fluid (ACSF) before a 30-min session in which pressing one lever delivered food pellets and pressing the other delivered fruit punch. Learning during this session was tested the next day by sating the animals on either the pellets or fruit punch before assessing their performance on the two levers in extinction. The ACSF group selectively reduced responding on the lever that, in training, had earned the now devalued outcome, whereas the APV group did not. Experiment 2 replicated the effect of APV during the critical training session but found no effect of APV given after acquisition and before test. Furthermore, Experiment 3 showed that the effect of APV on instrumental learning was restricted to the pDMS; infusion into the dorsolateral striatum did not prevent learning. These experiments provide the first direct evidence that, in instrumental conditioning, NMDARs in the dorsomedial striatum are involved in encoding action-outcome associations.

2-Amino-5-phosphonovalerate↗

Specificity of conditional associative-learning deficits in obsessive-compulsive disorder (OCD) and non-OCD anxiety disorders.

The acquisition of conditional associations using neutral and disease-related nouns was studied in 15 inpatients with obsessive-compulsive disorder (OCD), 15 inpatients with non-OCD anxiety disorders and 15 chronic pain inpatients. Patients were comparable with respect to age, sex, depression, intelligence, executive functions, verbal and spatial memory, visuoconstructive functions, and handedness. The investigation took place in the diagnostic phase prior to the patient's beginning a standardized behavioral treatment program. It was hypothesized that anxiety patients acquired disease-related material faster than pain patients but that only OCD patients show inferior performance with respect to neutral stimuli. Results show that the three patient groups were widely comparable concerning neuropsychological background measures and showed equivalent results with respect to disease-related stimuli. But OCD patients yielded an inferior degree of performance when neutral stimuli were used whereas non-OCD anxiety disorder and pain patients displayed an equivalent degree of performance both for neutral and disease-related material, respectively. Results are discussed within the framework of obsessive-compulsive spectrum disorders.

Adult↗