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Effects of midline and lateral cerebellar lesions on motor coordination and spatial orientation.

Rats were lesioned in the midline cerebellum, comprising the vermis and fastigial nucleus, or the lateral cerebellum, comprising the cerebellar hemispheres and dentate nucleus, and evaluated in a series of motor and non-motor learning tests. Rats with midline lesions had difficulty in maintaining their equilibrium on a bridge and were slower before turning upward and traversed less squares on an inclined grid. They were not impaired for muscle strength when suspended from a horizontal wire. Rats with lateral lesions had milder deficits on the bridge and were not affected in the other two tests. In the Morris water maze test, rats with lateral lesions were deficient in spatial orientation, whereas rats with midline lesions were deficient in visuomotor coordination. Lateral lesions had no effects on visual discrimination learning. These results illustrate the differential influence of midline as opposed to lateral cerebellar regions on both motor and non-motor behaviors. Fastigial nucleus lesions decreased the time spent in equilibrium and latencies before falling on the bridge and the distance travelled along the inclined grid but had no effect on muscle strength when suspended from the horizontal string. Quadrant entries and escape latencies were higher in rats with fastigial lesions during the hidden platform condition of the Morris water maze but not during the visible platform condition. It is concluded that fastigial-lesioned rats are impaired in equilibrium and spatial orientation but with repeated trials learn to improve their performances.

Analysis of Variance↗

Scotopic thresholds of rhesus monkeys at different grating densities under normal and low-protein diets.

Scotopic thresholds of rhesus monkeys were determined over a range of luminance levels, from 1138 to 17.8 x 10(-9) cd/cm2, and grating densities, from .132 to 1.58 lines per cm. The effects of a low-protein diet on these thresholds were also investigated, and standard stimulus objects within the discrimination learning situation were employed. Obtained thresholds decreased systematically from about 350 to 20 x 10(-9) cd/cm2, and there were no significant differences due to dietary protein level.

Animals↗

Conditional learning in aged rats: evidence of hippocampal and prefrontal cortex impairment.

Groups of normal old rats and young adult rats were administered a test of conditional discrimination learning in which different visual stimuli were associated with responses to different levers. Initially, rats were tested in a zero-delay condition in which they selected their responses in the presence of the conditional stimuli. They were later tested at 5- and 15-s delays between stimulus presentation and the appearance of the levers. Old rats were impaired in learning the basic conditional discrimination, a test thought to be sensitive to frontal lobe dysfunction. Age differences increased with the length of the interval, revealing a time-dependent memory loss that was attributed to impaired hippocampal function.

Aging↗

Effect of sex and age on brain monoamines and spatial learning in rats.

The concentrations of noradrenaline (NA), dopamine (DA), serotonin (5-HT), and their metabolites were measured in the prefrontal cortex, caudate-putamen, and hippocampus in young (3 months) and aged (27-31 months) Wistar rats of both sexes. Age-related changes were found in prefrontal NA and HVA/DA ratio, striatal DA and DOPAC/DA ratio, and striatal and hippocampal 5-HT and 5-HIAA/5-HT ratio. Age and sex dependent changes were found in striatal DA and DOPAC/DA ratio, and hippocampal MHPG-SO4/NA ratio. The aged rats were tested in spatial discrimination and reversal tasks in a T maze. The effects of alpha 2-agonist medetomidine (3 micrograms/kg) on the task performance were assessed in relation to individual variation in monoamine metabolism. Medetomidine impaired spatial discrimination learning of the aged rats by interacting with the hippocampal 5-HT turnover. Medetomidine improved reversal learning through an interaction with the striatal DA turnover and reduced the number of perseverative errors after reversal, mainly due to its interaction with the prefrontal NA turnover. It is concluded that the memory enhancing effect of drugs acting through the brain monoamine systems is highly dependent on the stage of degeneration of these systems that show considerable individual variation in aged animals.

Adrenergic alpha-Agonists↗

Pseudolearners in discrimination reversal.

This research investigated the shape of the acquisition and reversal functions in retardates' discrimination learning, with safeguards against suspected artifacts in other studies. A modified Wisconsin General Test Apparatus was used with 60 retardates in a 2 X 2 factorial design. Another 11 were classified as pseudolearners. The variables were the prereversal criteria and the number of irrelevant dimensions. After meeting criterion subjects were given 30 more trials for the detection of pseudolearners, but all received reversal training. Performance was stationary in both acquisition and reversal, suggesting all-or-none learning. For learners, differences of midreversal plateaus appeared which were opposite to predictions of the Zeaman and House (1963) theory. When pseudolearners were included, however, the plateau effect partially conformed to the theory.

Adolescent↗

Timing of nicotine effects on learning in zebrafish.

RATIONALE: Nicotine has been shown in many, but not all, studies to improve cognitive function in a number of species including rats, mice, monkeys, and humans. Recently, we have found that nicotine also improves memory in zebrafish. Nicotinic agonists are being developed as novel treatments for Alzheimer's disease and other cognitive impairments. OBJECTIVES: In screening the therapeutic potential of novel nicotinic agonists, it is important to have a rapid assay of cognitive improvement. Zebrafish can help with this effort. METHODS: We have developed a method of rapidly assessing spatial position discrimination learning in zebrafish in one session of seven trials. We used this method to determine the cognitive effects of nicotine. RESULTS: Nicotine (100 mg/l administered during 3 min of immersion) caused a significant improvement in percent correct performance. This dose was within the effective range we found to improve the choice accuracy performance of zebrafish using the more time-intensive delayed spatial alternation procedure. Interestingly, the positive effect of nicotine was seen at 20-40 min postadministration, but not earlier, and declined at 80 and 160 min posttreatment. At the 40-min postdosing interval, 200 mg/l nicotine was also found to significantly improve choice accuracy. Nicotine-induced accuracy improvement was reversed by the nicotinic antagonist mecamylamine given shortly before testing but not when given concurrently with nicotine. CONCLUSIONS: This position discrimination procedure in zebrafish effectively demonstrated the cognitive-enhancing effects of nicotine. This model may be useful in the early screening of novel nicotinic compounds for treatment of cognitive dysfunction.

Animals↗

Tryptophan depletion impairs stimulus-reward learning while methylphenidate disrupts attentional control in healthy young adults: implications for the monoaminergic basis of impulsive behaviour.

RATIONALE: Altered serotonergic and dopaminergic function have been widely implicated in behavioural disorders associated with impulsivity and risk-taking. However, little research has addressed the specific cognitive consequences of changed monoaminergic function that might contribute to the production of impulsive behaviour. OBJECTIVES AND METHODS: We compared the effects of rapid plasma tryptophan depletion, acute doses of the mixed indirect catecholamine agonist, methylphenidate (40 mg), and acute doses of the alpha(1)/alpha(2 )agonist, clonidine (1.5 microg/kg), on aspects of visual discrimination learning involving either acquisition of altered stimulus-reward associations (i.e. updating the affective valence of exteroceptive stimuli) or the control of attention towards relevant as opposed to irrelevant stimulus dimensions. RESULTS: Relative to subjects who received placebo, subjects with reduced tryptophan exhibited a deficit in the ability to learn changed stimulus-reward associations, but were still able to shift an acquired attentional set away from a now-irrelevant stimulus dimension towards a newly relevant dimension. By contrast, subjects who received methylphenidate were able to learn effectively about changing stimulus-reward associations, but showed an enhanced ability to shift an attentional bias, in combination with slowed response times. Subjects who received clonidine showed neither of these changes. CONCLUSIONS: These results suggest that reduction in central serotonin leads to altered neuromodulation of the cortical and subcortical regions (e.g. orbitofrontal cortex, striatum and anterior temporal structures) that mediate important aspects of associative learning whereby exteroceptive stimuli acquire altered incentive motivational value. On the other hand, facilitation of catecholamine neurotransmitters may disrupt the allocation of attention between relevant and irrelevant features of the environment, perhaps through altered modulation of the dorsolateral prefrontal cortex. The implications of these results for understanding the differential neuromodulation of cognitive functions are discussed.

Adolescent↗

[Correlation between ability of learning-memory and synaptosomal free [Ca2+]i in mice of different age].

In the present investigation, the behavior of learning and memory of 1-month and 6-month-old mice was studied by using Y-maze and one-trial passive avoidance response device. The synaptosomal free [Ca2+]i of four main brain regions (Hippocampus, Cerebral cortex, Cerebellum, Tectum of midbrain) of these mice were measured by fluorescent probe Ca2+ indicator Fura-2 and an AR-CM-MIC cation measurement system. The results showed that, in comparison with 1-month-old mice, the ability of discrimination learning and memory of 6-month-old ones were attenuated, and the synaptosomal free [Ca2+]i of hippocampus was increased.

Age Factors↗

Studies of marginal zinc deprivation in rhesus monkeys: infant behavior.

Rhesus monkey infants were marginally deprived of zinc (4 ppm diet) from conception and were compared to controls (100 ppm diet) during the first year of life in development of reflexes and motor patterns, mother-infant interaction, delayed response performance, discrimination learning and reversal, and open field behavior. Deficits in amount and variety of behavior were recorded in deprived infants; spontaneous locomotor activity was 50% below control levels in males at 1 mo of age; spontaneous activity was 7-10% lower in both males and females at 3 mo of age; response latencies were 50% lower than controls at 7-9 mo; failure to reach discrimination reversal criterion was seen in 71% of deprived infants as compared to 10% of controls at 10 mo of age; and abnormally low levels of climbing and exploration were seen in two of six deprived infants at 12 mo of age. No abnormalities in the rate of behavioral development or in emotional adaptability were observed. These and other results suggest that syndromes of lethargy, apathy, and hypoactivity are characteristic of behavioral effects of marginal zinc deprivation in primates.

Animals↗

Modifications and influences of tactual preferences for shape and texture.

The effects of pretraining on tactual preferences for shape and texture and the effects of the preferences on discrimination learning were investigated in three experiments using kindergarten and third grade children. The pretraining experience significantly affected the dimensional preferences in both age groups, while an unexpected significant sex difference indicated a stronger texture preference in girls. Children tended to learn faster when the dimension they preferred was relevant to the task, but girls were affected more strongly than boys. In all experiments, the girls' behavior closely resembled that predicted for younger children.

Behavior Therapy↗

Differential effects of neuropeptides on short-term memory in primates.

In a within-subject design, six rhesus monkeys (3 males and 3 females) received a 100 micrograms/kg injection of one of seven neuropeptides or a diluent control solution and were then tested for activity level, learning (discrimination reversal), short-term memory (delayed response), and for responsiveness to noxious stimuli. One daily injection was made with a different peptide for 10 consecutive days, including pre- and post tests on th first and last days with the diluent control. DSIP and D-Phe4-Met enkephalin seemed to produce some interference with short-term memory, while alpha-MSH showed some facilitation of it, as indicated by interactions of the peptides with the delay periods of 0, 15, or 30 sec. Sex differences were found in the learning task and the responsiveness to a noxious stimulus, suggesting the possibility of interactions between the peptides and endogenous hormones.

Animals↗

Ontogeny of eyeblink conditioning using a visual conditional stimulus.

The developmental emergence of associative learning in rodents is determined by interactions among sensory, motor, and associative systems that are engaged in a particular experimental preparation (Carter & Stanton, 1996; Hunt & Campbell, 1997; Rudy, 1992). In fear conditioning, chemosensory, auditory, and visual cues emerge successively as effective conditional stimuli (CS) during postnatal ontogeny. In the present study, we begin to examine the generality of this principle of sensory system development for eyeblink conditioning, a form of associative learning that develops substantially later than conditioned fear (Carter & Stanton, 1996). We asked whether the developmental emergence of eyeblink conditioning to a visual CS occurs at an age that is the same or different from conditioning to an auditory CS. In Experiment 1, rat pups were trained on postnatal Day 17 or 24 with experimental parameters (and design) that were identical to our previous studies of eyeblink conditioning except that presentation of a light rather than a tone served as the CS. The outcome was also identical: no eyeblink conditioning on Day 17 and strong conditioning on Day 24. In Experiment 2, conditioning to tone versus light was directly compared by means of a discrimination learning design on postnatal Days 19, 21, 23, and 31. There was no evidence for differential development of auditory versus visual eyeblink conditioning. The difference between this outcome and previous ones involving conditioned fear (Hunt & Campbell, 1997; Rudy, 1992) suggests that principles concerning sensory maturation and learning may be different for early- versus late-developing associative systems.

Amygdala↗

Lesions of the fornix but not the amygdala impair the acquisition of concurrent discriminations by rats.

Rats with lesions in either the fornix, the amygdala, or both were compared with control animals on the acquisition of three different concurrent object discrimination tasks. In the first task the animals received one trial per day on each of six pairs of stimulus objects ('spaced' condition). In the second task the animals received four trials per day on each of six stimulus pairs ('standard' condition), and in the last task the animals received 36 trials on each of two stimulus pairs in just a single day ('massed' condition). Animals with fornical lesions were impaired on all three conditions. In contrast, the amygdala lesions only affected the 'massed' condition and then only when the animals had to select the 'non-preferred' stimulus. Although animals with combined amygdala and fornical lesions were impaired on all three conditions there was no evidence that their deficit was greater than that in the animals with lesions restricted to just the fornix. In view of the evidence that concurrent discrimination learning offers an appropriate test for anterograde amnesia these findings are seen as consistent with the notion that the hippocampus, but not the amygdala, is critically involved in the mnemonic processes disrupted by amnesia.

Amygdala↗

Using stimulus shaping and fading to establish stimulus control in normal and retarded children.

The present study was an effort to investigate whether, in addition to his IQ level, the child's ability to identify all relevant stimulus components would affect the frequency of overselective responding. Children of different IQ levels (i.e. normal, educably retarded, and trainable retarded children) participated. Subjects were trained to learn the meanings of four sets of fictitious words, i.e. two sets containing words printed in Roman letters (Roman words), and two sets containing words printed in Hebrew letters (Hebrew words). All subjects could identify the words of each set. The normal and educably retarded subjects could read aloud the Roman words, whereas the trainable retarded subjects could not. None of the subjects could read the Hebrew words. Two training procedures were used, one requiring transfer of stimulus control (fading), and one which did not (stimulus shaping). The results indicated that, firstly, the discrimination learning of the normal and educably retarded subjects covaried with the IQ level and their ability to read the words. The learning rate was not affected by the training procedures. Secondly, the trainable retarded subjects learned much better through stimulus shaping than through fading. Their acquisition rates were slow and not affected by the types of letters. Thirdly, the training procedures had no effect on the breadth of stimulus control. Instead, it covaried as a function of the IQ level (all groups) and of the child's ability to read the words (normal and educably retarded subjects). Fourthly, the training procedures had, however, considerable effect on which letters controlled the discriminations. When overselective selective responding was evident, the letters that had been associated with the prompts were more often functional than the other letters, but only for the words trained through stimulus shaping.

Child↗

The development of inhibitory control in preschool children: effects of "executive skills" training.

As one of several processes involved in the executive functioning of the cognitive system, inhibitory control plays a significant role in determining how various mental processes work together in the successful performance of a task. Studies of response inhibition have shown that although 3-year-old children have the cognitive capacity to learn the rules required for response control, indicated by the correct verbal response, developmental constraints prevent them from withholding the correct response (Bell & Livesey, 1985; Livesey & Morgan, 1991). Some argue that these abulic dissociations are relative to children's ability to reflect on the rules required for response control (Zelazo, Reznick, & Pinon, 1995). The current study showed that repeated exposure to tasks facilitating the acquisition of increasingly complex rule structures could improve inhibitory control (as measured by a go/no-go discrimination learning task), even in children aged 3 years. These tasks included a variant of Diamond and Boyer's (1989) modified version of the Wisconsin Card Sort Task and a simplification of the change paradigm (Logan & Burkell, 1986). It is argued that experience with these tasks increased the acquisition of complex rules by placing demands on executive processes. This includes response control and other executive functions, such as representational flexibility, the ability to maintain information in working memory, the selective control of attention, and proficiency at error correction. The role of experiential variables in the development of inhibitory control is discussed in terms of the interaction between neural development and appropriate executive task experience in the early years.

Attention↗