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PubMedDate not supplied

Psychophysiological and behavioral differences as a function of age and Parkinson's disease.

Differences related to age and to specific neurological (Parkinsonian) damage were studied by contrasting, respectively, old (mean age 64 years) and young (27 years) subjects (N = 15), and old-normal (N = 15) and old-Parkinsonian (N = 15) subjects. Both behavioral as well as psychophysiological dependent variables were employed. The behavioral measure was performance on a discrimination learning task, while the psychophysiological measures were based on habituation to a repeated tone stimulus and on a Pavlovian differential conditioning preparation. The behavioral task showed predominantly age-related differences, with the young learning faster. Another age-related difference was interpreted as showing a more insight-like learning process in the young. Response-bias (beta) values did not differ between groups. Age-related differences also emerged more clearly than specific-neurological-damage differences in the psychophysiological data. The older subjects manifested markedly less autonomic conditioning, which was probably due to a lowering of reactivity, as well as the emergence of habituation to the (loud-noise) unconditional stimulus. A correlational analysis of discrimination conditioning also yielded age-related differences. Most notably, reactivity played a greater role in conditioning in the old than in the young subjects. The results illustrated how psychophysiological measures can provide information that complements those provided by behavioral measures.

Adult↗
PubMed2006

Rule learning and reward contingency are associated with dissociable patterns of dopamine activation in the rat prefrontal cortex, nucleus accumbens, and dorsal striatum.

The midbrain dopamine system has been ascribed roles in reward expectancy, error detection, prediction, and memory. However, these theories typically do not differentiate between dopamine response and action in different forebrain terminal fields. We measured dopamine release in the prefrontal cortex (PFC), nucleus accumbens (NAc), and dorsal striatum (DS) of rats exposed to the same maze apparatus under three behavioral conditions: a set-shift task in which reward depended on discrimination learning and extradimensional set-shifting, a yoked condition in which reward was intermittent and not under the control of the subject, and a "reward-retrieval" variant in which reward was certain on every trial. We found dissociable patterns of dopamine release associated with learning, uncertainty, and reward. Dopamine increased in all three regions when reward was contingent on rule learning and shifting or was uncertain. These increases were sustained after behavior. There was a significant correlation between the magnitude of increase in PFC dopamine and the rapidity with which rats shifted between discrimination rules. In the yoke condition, in which the receipt of reward was always uncertain, the opposite relationship between dopamine levels and likelihood of reward was observed. Predictable, noncontingent reward was associated with increased dopamine levels in the NAc and DS. In contrast, PFC dopamine did not increase significantly above baseline levels. Thus, the dopaminergic projections to the PFC and nucleus accumbens were selectively, yet differentially, activated in situations of uncertainty and cognitive demand, whereas the dopaminergic projection to the DS responded independently of task differences in learning and reward.

Animals↗
PubMed1990

Dopamine and ACh involvement in plastic learning by hypothalamic neurons in rats.

Unit activity in the rat lateral hypothalamus (LHA) was recorded during discrimination learning of cue tone stimuli (CTS). CTS+ predicted reward (glucose or intracranial self-stimulation); CTS- predicted aversion (electric shock or tail pinch); and all behavior responses were by the same act, licking. Roles of the LHA dopaminergic and cholinergic systems in CTS learning were investigated by electrophoretic application of dopamine (DA) and acetylcholine (ACh), and their antagonists. The CTS+, the predicted reward and DA, all had similar effects (inhibition) on many LHA neurons; and these were all opposite to the effects (excitation) of CTS-, the predicted aversion, and ACh. Neural responses to CTS+ were blocked by spiperone, and responses to CTS- were blocked by atropine. Sensitivity of LHA neurons to DA was reduced by extinction of CTS+ learning for reward, and sensitivity to ACh was reduced by CTS- learning for aversion. The data suggest that afferent DA and ACh inputs to LHA neurons are essential for plastic CTS+ and CTS- learning.

Acetylcholine↗
PubMed1987

Discriminative stimulus properties of ethosuximide in the pigeon.

After initial exposure to 80 mg/kg, pigeons trained on a two-key drug discrimination procedure rapidly learned to discriminate 120 mg/kg ethosuximide from saline. When 40-160 mg/kg doses of ethosuximide were administered during generalization tests, the percentage of responses directed to the ethosuximide-appropriate key varied directly with dose. Time-effect determinations revealed that the discriminable properties of ethosuximide were evident as early as 15 min after, and as late as 2 h after, intramuscular injection. The discriminative stimulus properties of ethosuximide failed to generalize to the anticonvulsant compounds clonazepam (0.5-4 mg/kg), methsuximide (25-200 mg/kg), and phenytoin (5-15 mg/kg). Generalization was apparent with certain doses of primidone (250, 300 mg/kg) and mephenytoin (80, 160, 240 mg/kg). The concomitant administration of pentylenetetrazol (5, 10, 20 mg/kg) partially blocked the discriminable properties of the training dose of ethosuximide.

Animals↗
PubMed1998

The hippocampus as an associator of discontiguous events.

The hippocampus has long been thought to be an important cortical region for associative learning and memory. After several decades of experimental and theoretical studies, a picture is emerging slowly of the generic types of learning tasks that this neural structure might be essential for solving. Recently, there have been attempts to unify electrophysiological and behavioral observations from rodents performing spatial learning tasks with data from primates performing various tests of conditional and discrimination learning. Most of these theoretical frameworks have rested primarily on behavioral observations. Complementing these perspectives,we ask the question: given certain physiological constraints at the neuronal and cortical level, what class of learning problems is the hippocampus, in particular, most suited to solve? From a computational point of view, we argue that this structure is involved most critically in learning and memory tasks in which discontiguous items must be associated, in terms of their temporal or spatial positioning, or both.

Animals↗
PubMed1986

Lateral hypothalamus neuron involvement in integration of natural and artificial rewards and cue signals.

Involvement of rat lateral hypothalamus (LHA) neurons in integration of motivation, reward, and learning processes was studied by recording single-neuron activity during cuetone discrimination, learning behavior to obtain glucose, or electrical rewarding intracranial self-stimulation (ICSS) of the posterior LHA. To relate the activity of an LHA neuron to glucose, ICSS, and anticipatory cues, the same licking task was used to obtain both rewards. Each neuron was tested with rewards alone and then with rewards signaled by cuetone stimuli (CTS), CTS1+ = 1,200 Hz for glucose, CTS2+ = 4,300 Hz for ICSS, and CTS- = 2,800 Hz for no reward. The activity of 318 neurons in the LHA was analyzed. Of these, 212 (66.7%) responded to one or both rewarding stimuli (glucose, 115; ICSS, 193). Usually, both rewards affected the same neuron in the same direction. Of 96 neurons that responded to both rewards, the responses of 72 (75%) were similar, i.e., either both excitatory or both inhibitory. When a tone was associated with glucose or ICSS reward, 81 of the 212 neurons that responded to either or both rewards and none of 106 neurons that failed to respond to either reward acquired a response to the respective CTS. Usually, the response to a tone was in the same direction as the reward response. Of 45 neurons that responded to both glucose and CTS1+, 38 (84.4%) were similar, and of 66 that responded to both ICSS and CTS2+, 47 (71.2%) were similar. The neural response to a tone was acquired rapidly after licking behavior was learned and was extinguished equally rapidly before licking stopped in extinction. The latency of the neural response to CTS1+ was 10-150 ms (58.7 +/- 40.9 ms, mean +/- SE, n = 31), and that of the first lick was 100-370 ms (204.8 +/- 59.1 ms, n = 31). The latency of neural responses to CTS2+ was 10-230 ms (68.3 +/- 53.5 ms, n = 33), and that of the first lick was 90-370 ms (212.4 +/- 58.5 ms, n = 33). There was no significant difference between the neural response latencies for the two cue tones nor between the lick latencies for the different rewards. Neurons inhibited by glucose or ICSS reward were distributed widely in the LHA, whereas most excited neurons were in the posterodorsal subarea; fewer were in the anteroventral subarea. Neurons responding to the CTS for glucose or ICSS were found more frequently in the posterior region.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMedDate not supplied

Auditory processing disorders and problems with hearing-aid fitting in old age.

The hearing handicap experienced by elderly subjects depends only partially on end-organ impairment. Not only the neural unit loss along the central auditory pathways contributes to decreased speech discrimination, but also learning processes are slowed down. Diotic listening in elderly people seems to fasten learning of discrimination in critical conditions, as in the case of sensitized speech. This fact, and the binaural gain through the binaural release from masking, stress the superiority, on theoretical grounds, of binaural over monaural hearing-aid fitting.

Acoustic Stimulation↗
PubMed1998

Simultaneous learning of motion discrimination in two directions.

We take issue with theories about the direction specificity in perceptual learning of motion discrimination. Trials of motion discrimination in two opposite directions were interleaved in uneven proportions (2:1). Human subjects improved faster in the direction with less frequent trials, indicating that learning transferred from the more frequent to the less frequent direction.

Adult↗
PubMed1975

"Stimulus generalization" between differentiated visual, auditory, and central stimuli.

Cats were trained to discriminate between two different repetition rates of flicker and of click. Both approach-approach and avoidance-avoidance discriminations were used. After substantial overtraining, transfer of frequency discrimination was initiated to stimulation of the reticular formation using bursts of electrical pulses at the same two repetition rates. Significant levels of discriminated performance were obtained in all cats very quickly, indicating good cross-modal transfer between the peripheral discriminanda and the central stimuli. The literature on stimulus generalization and cross-modal transfer is reviewed and the findings of this experiment are discussed in that context. Certain conditions are defined which, if satisfied, justify the interpretation that stimulus generalization or rapid cross-modal transfer indicate that facilitation of subsequent tasks in a training sequence can be attributed to mediation by a specific neuronal mechanism established by training on a previous task. The present experiment was designed in view of such criteria. The evidence of good cross-modal transfer is interpreted to mean that brain mechanisms storing memories about discriminations between visual or auditory stimuli with different repetition rates can be effectively activated by gross electrical stimuli at the same repetition rates. Conflict trials were then carried out in which flicker or click at either frequency was contradicted by concurrent RF stimuli at the other frequency. As the current level of RF stimuli was parametrically increased, it was found that the central stimuli achieved almost complete control over the behavioral outcome in most cases. Concurrent transfer of training, using a counterbalanced training sequence, was then carried out to stimulation of the visual cortex, lateral geniculate, medial geniculate, and the intralaminar nuclei of the thalamus. In each case, rapid transfer was displayed by at least one animal. Once performance to brain stimulation at a given repition rate was established, little change was observed when the fine structure of the stimulus was altered by changing parameters of the stimulus burst. These findings are interpreted as providing support for a statistical theory of memory, since they constitute evidence that previously learned discriminative behavior can readily be elicited by compelling large ensembles of neurons in various brain regions to discharge with particular temporal patterns. It is difficult to reconcile these results with theories which postulate that learning establishes new synaptic pathways in which discharge must occur for memories to be retrieved.

Animals↗
PubMed1998

The uterine environment enhances cognitive competence.

Genetically identical mouse embryos were transferred into same-strain uteri (transfer controls) or into hybrid uteri. A third group was not transferred. When adult, the mice were given a series of behavioral tests. In-strain transfer controls differed from non-transfer mice only on two activity measures, and did not differ on any cognitive variable. In contrast, mice reared in hybrid uteri were found to be superior to in-strain transfer mice on discrimination learning. Lashley maze learning and Morris maze learning; they also showed better adaptation in an avoidance learning shuttlebox. To our knowledge this is the first study showing that the uterine environment can have a general enhancing effect upon cognitive competence across a broad range of behaviors.

Animals↗
PubMed1987

Effects of arecoline and pilocarpine on learning ability in marmosets pretreated with hemicholinium-3.

Common marmosets (Callithrix jacchus) were trained to perform serial reversal position discrimination tasks in a Wisconsin General Test Apparatus. Intraventricular injection of hemicholinium-3 4 h before testing resulted in a profound impairment of position discrimination learning which could be overcome by the intramuscular administration of low doses of the muscarinic agonists, arecoline or pilocarpine.

Animals↗
PubMed2001

Effects of selective thalamic and prelimbic cortex lesions on two types of visual discrimination and reversal learning.

The effects of excitotoxic lesions of the mediodorsal nucleus of the thalamus, the anterior thalamic nuclei and of the prelimbic cortex were examined on two tests of discrimination and reversal learning. In experiment 1A (visual discrimination and reversal), rats were required to discriminate two stimuli, and respond to the stimulus associated with reward (the S+ stimulus). There was no effect of lesion on acquisition of this task. However, when stimulus-reward contingencies were reversed, animals with lesions of the mediodorsal nucleus of the thalamus made significantly more errors than control animals or animals of other lesion groups. In experiment 1B (conditional discrimination), animals were required to learn a rule of the type 'If stimulus A then go left, if stimulus B then go right'. No main effect of lesion on acquisition was observed in this experiment. To test the generality of the reversal effect obtained in experiment 1A, a second cohort of animals with the same lesions was tested on acquisition of the visuospatial conditional task immediately postsurgery, followed by the reversal of the conditional rule (experiment 2). As in experiment 1B, no main effect of lesion group was observed during acquisition of the task. However, lesions of the mediodorsal nucleus of the thalamus resulted in a mild impairment according to number of sessions required to attain criterion performance of the task when the response rule was reversed. The results of the present study provide evidence for a role for the mediodorsal nucleus of the thalamus in new learning, particularly when stimulus-reward contingencies are reversed. Furthermore, they show that the functions of this thalamic nucleus can be dissociated from those of the anterior thalamus and the prelimbic cortex.

Animals↗
PubMed2005

Neurocognitive and psychotiform behavioral alterations and enhanced hippocampal long-term potentiation in transgenic mice displaying neuropathological features of human alpha-mannosidosis.

Mice with alpha-mannosidase gene inactivation provide an experimental model for alpha-mannosidosis, a lysosomal storage disease with severe neuropsychological and psychopathological complications. Neurohistological alterations in these mice were similar to those in patients and included vacuolations and axonal spheroids in the CNS and peripheral nervous system. Vacuolation was most prominent and evenly distributed in neuronal perikarya of the hippocampal CA2 and CA3 regions, whereas CA1 and dentate gyrus were weakly or not affected. Field potential recordings from CA1 region in hippocampal slices showed enhanced theta burst-induced long-term potentiation (LTP) in alpha-mannosidase-deficient mice. Longitudinal assessment in age-matched alpha-mannosidase-deficient and wild-type littermates, using an extended test battery, demonstrated a neurocognitive and psychotiform profile that may relate to the psychopathological alterations in clinical alpha-mannosidosis. Brainstem auditory-evoked potentials and basic neuromotor abilities were not impaired and did not deteriorate with age. Exploratory and conflict tests revealed consistent decreases in exploratory activity and emotional blunting in the knock-out group. alpha-Mannosidosis mice were also impaired in aversively motivated learning and acquisition of signal-shock associations. Acquisition and reversal learning in the water maze task, passive avoidance learning in the step-through procedure, as well as emotional response conditioning in an operant procedure were all impaired. Acquisition or shaping of an appetitive instrumental conditioning task was unchanged. Appetitive odor discrimination learning was only marginally impaired during shaping, whereas both the discrimination and reversal subtasks were normal. We propose that prominent storage and enhanced LTP in hippocampus have contributed to these specific behavioral alterations in alpha-mannosidase-deficient mice.

Animals↗
PubMed1990

Acute tolerance to ethanol using drug discrimination and open-field procedures in rats.

This study examined the phenomenon of acute tolerance to ethanol (ETOH) using drug discrimination learning (DDL), and open-field (OF) procedures. In DDL, rats were trained to discriminate between ETOH (1.2 g/kg) and saline. Doses of ETOH lower (0.6 and 0.9 g/kg), or higher (1.8 and 2.4 g/kg) than the training dose were tested to examine possible influence of ETOH pretreatment doses on the expression of acute tolerance. To assess concentrations of ETOH in the organism, a rebreathed air procedure was used. Equal concentrations after different ETOH doses were achieved by postponing the tests until sufficient time had elapsed. Only doses of ETOH higher than the training dose produced acute tolerance in the DDL procedure. For the response-time data no acute tolerance was observed. In the OF experiment, the occurrence of acute tolerance was examined for different spontaneous behaviours in drug-naive animals. At equal ETOH concentrations, the group examined during the descending phase of intoxication (1.8 g/kg, 60 min post-injection), reared significantly more than the group tested during the ascending phase (1.5 g/kg, 10 min post-injection). Other OF behaviours did not differ significantly between the two time intervals. Thus, it is suggested that acute tolerance is seen both in ETOH naive and in ETOH pre-exposed rats. However, in DDL acute tolerance was observed only when doses higher than training dose of ETOH were evaluated.

Animals↗
PubMed1993

An assessment of the interaction between cholecystokinin and the opiates within a drug discrimination procedure.

Recently, cholecystokinin (CCK) has been reported to antagonize a variety of opiate-induced effects, including nociception, body shaking, thermoregulation, and locomotion. Consistent with these results, a number of CCK antagonists potentiate the opiates in a range of behavioral and physiological assessments. The present study further examined the interaction between CCK and the opiates within the conditioned taste aversion baseline of drug discrimination learning, a design that utilizes the stimulus properties of the drug to control consummatory behavior. Specifically, animals injected with CCK prior to saccharin-LiCl pairings and the CCK vehicle prior to saccharin alone rapidly acquired the CCK-vehicle discrimination, avoiding saccharin consumption following the administration of CCK and consuming the same saccharin solution following the vehicle. Although the stimulus properties of CCK did not generalize to either naloxone or diprenorphine, morphine blocked and naloxone potentiated CCK's stimulus effects. These data are thus consistent with a physiological (rather than a pharmacological) interaction between CCK and the opiates.

Animals↗