Effects of differential interference with postnatal cerebellar neurogenesis on motor performance, activity level, and maze learning of rats: a developmental study

The region of the cerebellum was X-irradiated in infant rats with selected exposure schedules designed to produce animals in which the cerebellar cortex was (a) essentially normal except for agenesis of late forming granule cells with axons situated in the uppermost molecular layer (12--15X), (b) lacking in stellate cells, with a severe reduction in granule cells with axons in the upper molecular layer (8--15X), (c) morphologically disorganized but had only intermediate cell agenesis (4--5X), or (d) disorganized and devoid of practically all postnatally forming interneurons (4--15X). In the first two experiments young adults had to traverse rotating rods that differed in texture and types of obstacles. The 8--15X animals showed no deficits on any of the rods tested. The third study dealt with spontaneous motor performance in the open field at three ages. The 4--5X and 4--15X animals were hypoactive as infants and young adults; this was attributed to their motor deficits. The 8--15X and 12--15X animals were hyperactive in the open field as young adults. The fourth experiment examined intra- and/or intersession habituation. No group differences were found in habituation patterns. In the fifth experiment, using activity wheels, the 4--15X group was hypoactive, and the 8--15X and 12--15X groups were hyperactive as young adults. In the sixth experiment young adults were tested for learning performance in a multiple-unit water maze. The 4--15X group was deficient on single alternation; the 4--5X and 12--15X groups on double alternation. The seventh experiment shed some light on the single alternation deficit of the 4--15X group; only these animals failed to alternate spontaneously in a nonaversive situation. In conclusion, these behavioral results, combined with those of recent morphological investigations, suggest that the cerebellar cortex is hierarchically organized: The basal domain of Purkinje cells and the lower molecular layer are implicated in the coordination of movements; the apical domain of Purkinje cells and the upper molecular layer, in the coordination of actions.     

Preoperative enrichment and behavioral recovery in rats with septal lesions

To assess the behavioral effects of preoperative differential housing male rats were placed in either enriched or isolated environments at weaning prior to receiving either sham operations or septal lesions when 57 days of age. Rats with septal lesions showed reduced habituation of ambulation and initially made fewer rears in an empty open field but made more object-contacts coupled with a lack of habituation in the object-filled field. Septal rats also showed severe impairments when tested in a 12-arm radial maze with 7 arms baited and 5 arms unbaited. Preoperative enrichment did not significantly affect these lesion-induced changes. Nevertheless, enrichment significantly lowered ambulation (but did not affect habituation) in the open field and increased the number of manipulatory relative to nonmanipulatory contacts. However, preoperatively enriched septal rats showed a deficit in spontaneous alternation (45%) in contrast to the high levels (83%) shown by intact enriched rats, whereas both intact and septal isolated rats showed similar levels of spontaneous alternation (68%). These results conflict with earlier reports that preoperative enrichment "protects" rats against the deficits produced by septal lesions.     

Habituation under stress: shocked mice show nonassociative learning in a T-maze

Conflicting predictions of reinforcement and neophobia-arousal theories were evaluated in a simple choice task. Four groups of C57BL/6J mice were administered daily two-trial tests in a uniform T-maze for 10 consecutive days. For three groups, the contingencies of footshock treatments were manipulated to reinforce alternation, perseveration, or both. A control group that was not administered footshock alternated, but all three groups that were stressed perseverated more and more across tests, despite the differences in reinforcement contingencies. These results are inconsistent with the predictions of reinforcement theory but consistent with the view that stressed or aroused animals are neophobic and use nonassociative learning (habituation) to distinguish between novel and familiar alternatives.     

Reward, novelty and spontaneous alternation

It has been suggested that rats' propensity for “win-shift” behaviour in spatial memory and spontaneous alternation tests reflects a species-specific foraging strategy which leads them to avoid places where they have recently found food. An alternative explanation is that they avoid places which are familiar. In three experiments using a T-maze, we evaluated these accounts by comparing the probability of avoiding or re-entering a recently visited arm, as a function of whether food had or had not been found on the previous visit. Each rat received a series of 16 exposure-test trial pairs over 8 days. Neither alternation nor repetition of the previous choice was differentially reinforced. Experiments I and II forced rats to enter a specific arm before a subsequent choice, and differed in the overall probability of reward; in Experiment III all choices were free. In all three experiments the probability of alternating was greater after nonreward than after reward. This effect occurred more reliably on later tests within a day, little difference appearing on earlier tests. It was concluded that there was no evidence for a spontaneous “win-shift” tendency as such, and that these and other results can be adequately accounted for by a combination of exploratory tendencies (spontaneous alternation) and the conventional effects of reward.     

Scopolamine-induced deficits in spontaneous alternation performance: attenuation with lateral ventricle injections of glucose.

This experiment determined whether centrally administered glucose can attenuate scopolamine-induced deficits in spontaneous alternation performance. All rats were surgically prepared with indwelling cannulae directed at the lateral ventricle. Thirty min prior to alternation tests, rats received systemic (ip) injections of saline or scopolamine (3 mg/kg). Ten or thirty min prior to training, the rats also received a direct injection into the lateral ventricle of either artificial cerebrospinal fluid (CSF) or glucose (3 micrograms in 1 microliter). Scopolamine significantly impaired spontaneous alternation performance relative to controls. Additional treatment with ICV glucose 30 min, but not 10 min prior to testing, significantly attenuated the scopolamine-induced deficit. These results add support to the view that glucose acts directly on brain systems to attenuate behavioral effects of cholinergic antagonists.     

Analysis of variances and covariances is misleading as a guide to a common factor model

The “factor” analyses published by Schultz, Kaye, and Hoyer (1980) confused component and factor analysis and led in this case as in many others to unwarranted conclusions. They used component analysis to develop factor models that were subjected to restricted (confirmatory) maximum likelihood analysis, but the final models for which good fits with the observed correlations were obtained were not common factor models. They were, however, discussed as such and conclusions drawn accordingly. When their correlation matrices are analyzed by the principal factors method, two factors are sufficient to account for the intercorrelations. These two factors generally support the a priori expectation of a difference between intelligence tasks and spontaneous flexibility tasks. They are also quite similar in younger and older subjects, when similarity is judged in terms of factor pattern. Factor loadings for the younger subjects, however, are much smaller than expectations based on the respective ranges of talent in the two groups of subjects or on past experience with similar tests in undergraduate student populations.     

VITESSE D'HABITUATION VISUELLE CHEZ DES BÉBÉS IVOIRIENS ET FRANÇAIS

A comparison of the habituation rate of two infant populations was performed: Ivory Coast and French 3-, 5- and 8-month-olds. The same age evolution of the habituation performance was observed, but no differences were found between the two cultures at any age. The African infant's lead in development as shown by infant tests is not observed with the habituation paradigm. If such data are confirmed, they will lead to the conclusion that the difference is more a motor than a cognitive one.     

Sustained attention in children at risk for schizophrenia: Findings with two visual continuous performance tests in a new sample

In partial replication of an earlier study, 35 children at high risk for schizophrenia, 25 children at high risk for affective disorder, and 53 normal control children from a new sample of 7- to 12-year-old subjects were tested with two new visual continuous performance tests. Response levels and intrasubject variability were analyzed separately. Multivariate analyses on factor scores derived from response levels indicate that "groups" is a significant predictor for a factor reflecting discriminability (or sensitivity) for the more difficult of these tests but not for the less difficult one, and that high risk for schizophrenia is associated with lower performance. Factor scores and multiple regression analyses were used to dichotomize subjects as to whether or not they are low performance outliers. A significantly larger proportion of subjects from the high risk for schizophrenia group than from the control groups were low performance outliers. Among subjects that developed psychopathology in adolescence, subjects at high risk for schizophrenia were more likely to have contributed low performance outliers early during childhood.     

Attenuation of Morphine-Induced Behavioral Changes in Rodents byd-andl-Glucose

Administration ofd-glucose enhances learning and memory in several tasks and also attenuates memory impairments and other behavioral effects of several drugs, including morphine. The present experiment compared the effects of peripherally administeredd-glucose with those ofl-glucose, a stereoisomer ofd-glucose that is not metabolized and does not readily cross the blood–brain barrier. Liked-glucose, though at somewhat different doses, peripherally administeredl-glucose attenuated morphine-induced deficits in spontaneous alternation performance in rats and mice and attenuated morphine-induced hyperactivity in mice.l-Glucose did not raise circulating levels of plasmad-glucose, suggesting that the effects ofl-glucose are not secondary to increased availability ofd-glucose. Using direct injections ofd- andl-glucose and morphine into the medial septum of rats, the findings indicate thatd-glucose but notl-glucose attenuated morphine-induced deficits in spontaneous alternation performance; indeed, intraseptal injections ofl-glucose alone impaired spontaneous alternation performance. These findings suggest that peripherall-glucose antagonizes morphine-induced behavioral effects by a peripheral signaling mechanism, one distinct from the mechanisms that mediate at least some of the effects ofd-glucose on brain function.     

The role of exploration in win-shift and win-stay performance on a radial maze

Win-shift spatial memory tasks in a radial maze reinforce animals for avoiding previously visited rewarded arms; win-stay tasks reinforce them for returning to those arms. Win-shift tasks have generally been found much easier to perform, and this may be explained either in terms of foraging models which postulate avoidance of locations where food has been found, or in terms of the predominance of spontaneous alternation (exploration). Experiment 1 examined spontaneous alternation behavior in the radial maze as a function of whether the first visit to an arm had been rewarded or not, and showed that alternation was more probable after nonreward than after reward in both hungry and thirsty rats (a result which conflicts with the foraging account of the win-shift superiority). Experiment 2 replicated the finding that win-stay discrimination performance was inferior to win-shift. A manipulation (lengthening the delay between initial and test choices) which weakens spontaneous alternation, reduced, but did not reverse, the win-shift superiority. In Experiment 3, in order to eliminate the influence of spontaneous alternation, versions of the win-stay and win-shift tasks were devised in which, unlike the original task, all arms were familiar at the choice trial. Under those conditions win-stay was performed better than win-shift. It is concluded that spontaneous alternation plays a major role in many spatial memory tasks, and that the results can best be accounted for by combining principles of exploration and simple associative learning, without recourse to foraging models.     

Age differences in within-session habituation of exploratory behavior: effects of stimulus complexity

The effects of age on the habituation of exploratory behavior of 8-month- and 28-month-old male C57BL/NNia mice were examined under three different stimulus complexity conditions. Increases in the degree of stimulus complexity resulted in an attenuation of between-session habituation and an initial disruption of within-session habituation by 8-month-old mice. Although increases in stimulus complexity also resulted in an increase in the overall level of exploration by aged mice, stimulus complexity was not found to have a systematic effect on between- or within-session habituation by aged mice. No between-session habituation was observed in aged mice under any of the stimulus complexity conditions. Further, aged mice exhibited significant within-session increases, rather than decreases, in exploration under each stimulus complexity condition. This disruption of within-session habituation in aged mice was found to persist over four daily test sessions. In view of the specific patterns of exploration by aged mice, the disruption of within-session habituation was attributed to age-related differences in reactivity to the arousal-inducing properties of novel stimuli.     

Influence of dorsal hippocampal lesions and MMP inhibitors on spontaneous recovery following a habituation/classical conditioning head–shake task

The present investigation combined a classical conditioning paradigm with a head–shake response (HSR) habituation task in order to evaluate the importance of dorsal hippocampal neural plasticity to spontaneous recovery. In the first experiment animals exhibited rapid HSR habituation (air stimulus to the ear) and an 85% level of spontaneous recovery following a 24 h inter-session interval. The addition of a brief tone prior to the air stimulus produced a similar pattern of habituation during the first session, but the level of spontaneous recovery was reduced (44%) during Session II. In a second experiment dorsal hippocampal lesioned rats placed on this tone/HSR paradigm responded with an 87% level of spontaneous recovery during Session II; while neocortex lesioned control rats indicated significantly reduced levels of spontaneous recovery (55%). In a third experiment bilateral injections of a general MMP inhibitor, FN-439, into the dorsal hippocampus resulted in high levels of spontaneous recovery (81%); while control rats injected with artificial cerebrospinal fluid displayed a significant attenuation of spontaneous recovery (45%). Finally, animals bilaterally injected with a specific MMP-3 inhibitor into the dorsal hippocampus indicated very similar results to those obtained following FN-439 injection. These findings indicate that animals prepared with dorsal hippocampal lesions, or injections with an MMP inhibitor, revealed an impaired association between the tone and air stimulus thus maximum spontaneous recovery was present 24 h later. Thus, it appears that the dorsal hippocampus influences habituation by conserving responses and reducing spontaneous recovery when a temporally contingent signaling cue is present.     

Telemetry provides new insights into entrainment of activity wheel circadian rhythms and the role of body temperature in the development of ulcers in the activity-stress paradigm

Two methods of monitoring the circadian rhythm of activity in rodents: (1) an activity wheel cage, which detects the number of wheel revolutions, and (2) an internal radio transmitter, which records gross motor activity (GMA) of the animal, were compared in both normal circadian cycles and during the development of activity-stress ulcers. Rats were implanted with a biotelemetry transmitter that detected GMA and body temperature (BT) and placed in activity wheel cages. A 12 hour/12 hour light/dark cycle was maintained throughout the experiment. Subjects were subdivided into two groups: (1) unlimited access to activity wheel (AW) cages and (2) locked activity wheel (LW) cages. Following an ad-libitum habituation period, animals were allowed food access for 1 hour/day during the light. In the habituation period, the animals showed higher GMA and BT during the dark phase when housed in AW cages than in LW cages. Both GMA and number of wheel revolutions increased dramatically after the onset of food restriction for the AW animals. There was a deleterious drop in BT in AW animals as the food-restricted period continued and a significant correlation existed between severity of ulcerations and BT. The findings of this experiment demonstrate that the activity wheel imposes an alternation of the circadian cycle, which, in turn, influences rhythmicity through reentrainment. Additionally, in the activity-stress paradigm, a significant drop in BT correlates with severity of ulcerations. A disrupted circadian cycle, involving hypothermia, is proposed as the mechanism underlying the demise of animals in the activity-stress paradigm.     

Response bias and the measurement of choice alternation

The problem of devising a measure of alternation of choices that is independent of response bias is considered. Previous solutions are equivalent to the correction for chance guessing in the Yes/No experiment of psychophysics, and require an estimate of response bias, usually from choices on the first of two daily trials. This involves the questionable assumption that response bias is homogeneous over time or across subjects. It is suggested that spontaneous alternation is analogous to the two alternative forced choice situation of psychophysics, and the fourfold point correlation is proposed as an index of alternation that is statistically independent of response bias. Implications for interpreting the effect upon spontaneous alternation of hippocampal and other lesions are considered.     

Telemetry Provides New Insights into Entrainment of Activity Wheel Circadian Rhythms and the Role of Body Temperature in the Development of Ulcers in the Activity-Stress Paradigm

Two methods of monitoring the circadian rhythm of activity in rodents: (1) an activity wheel cage, which detects the number of wheel revolutions, and (2) an internal radio transmitter, which records gross motor activity (GMA) of the animal, were compared in both normal circadian cycles and during the development of activity-stress ulcers. Rats were implanted with a biotelemetry transmitter that detected GMA and body temperature (BT) and placed in activity wheel cages. A 12 hour/12 hour light/dark cycle was maintained throughout the experiment. Subjects were subdivided into two groups: (1) unlimited access to activity wheel (AW) cages and (2) locked activity wheel (LW) cages. Following an ad-libitum habituation period, animals were allowed food access for 1 hour/day during the light. In the habituation period, the animals showed higher GMA and BT during the dark phase when housed in AW cages than in LW cages. Both GMA and number of wheel revolutions increased dramatically after the onset of food restriction for the AW animals. There was a deleterious drop in BT in AW animals as the food-restricted period continued and a significant correlation existed between severity of ulcerations and BT. The findings of this experiment demonstrate that the activity wheel imposes an alternation of the circadian cycle, which, in turn, influences rhythmicity through reentrainment. Additionally, in the activity-stress paradigm, a significant drop in BT correlates with severity of ulcerations. A disrupted circadian cycle, involving hypothermia, is proposed as the mechanism underlying the demise of animals in the activity-stress paradigm.     

Sex differences in aversive memory in rats: Possible role of extinction and reactive emotional factors

Studies usually show better spatial learning in males and stronger emotional memory in females. Spatial memory differences could relate to diverse strategies, while dissimilar stress reactions could cause emotional memory differences. We compared male and female rats in two emotional (classical emotional conditioning and aversive discrimination memory) and two emotionally “neutral” tasks: (1) plus-maze discriminative avoidance, containing two open and two enclosed arms, one of which presenting aversive stimuli (light/noise). No differences were found in learning, retrieving, or basal emotional levels, while only male rats presented extinction of the task; (2) contextual fear conditioning – a cage was paired to mild foot shocks. Upon reexposure, freezing behavior was decreased in females; (3) spontaneous alternation – the animals were expected to alternate among the arms of a four-arm maze. No differences between genders were found and (4) open-field habituation was addressed in an arena which the rats were allowed to explore for 10 min. Habituation was similar between genders. Differences were found only in tasks with strong emotional contexts, where different fear responses and stress effects could be determinant. The lack of extinction of discriminative avoidance by females points out to stronger consolidation and/or impaired extinction of aversive memories.     

Habituation in normal and down's syndrome fetuses

The ability of ten normal and two Down's syndrome fetuses to habituate to a repeated auditory stimulus was assessed. The normal fetuses were assessed on two separate occasions during the final trimester of pregnancy. The number of trials to habituate and latency to respond were recorded. The results demonstrated that all normal fetuses exhibited a decrement in response to repeated presentations of the stimulus, a 250-Hz sine wave. This was the result of habituation and not fatigue since fetuses recovered responding upon presentation of a new (500 Hz) stimulus and habituated faster on re-presentation of the original stimulus. The performance of fetuses remained stable over the two testing periods. The response of the Down's syndrome fetuses was different to that of normal fetuses rarely overlapping indices of habituation exhibited by normal fetuses. The study concludes that habituation may be a powerful tool to examine the behavioural and sensory development of the fetus and may be of use in the antenatal assessment of the existence and severity of neural abnormality.     

Habituation in normal and Down's syndrome fetuses.

The ability of ten normal and two Down's syndrome fetuses to habituate to a repeated auditory stimulus was assessed. The normal fetuses were assessed on two separate occasions during the final trimester of pregnancy. The number of trials to habituate and latency to respond were recorded. The results demonstrated that all normal fetuses exhibited a decrement in response to repeated presentations of the stimulus, a 250-Hz sine wave. This was the result of habituation and not fatigue since fetuses recovered responding upon presentation of a new (500 Hz) stimulus and habituated faster on re-presentation of the original stimulus. The performance of fetuses remained stable over the two testing periods. The response of the Down's syndrome fetuses was different to that of normal fetuses rarely overlapping indices of habituation exhibited by normal fetuses. The study concludes that habituation may be a powerful tool to examine the behavioural and sensory development of the fetus and may be of use in the antenatal assessment of the existence and severity of neural abnormality.     

Habituation and the human evoked potential

Habituation of human scalp-recorded cerebral evoked potentials was studied in response to auditory and visual repetitive stimuli of different intensities. Changes in magnitudes of evoked potentials with stimulus repetition were examined according to the parametric characteristics of habituation, generalization, and dishabituation. In addition, tests of the predictions of two theories of habituation were made regarding the degree and direction of intensity generalization of habituation. Both auditory and visual evoked potentials exhibited decrements in response magnitudes across the repetitive stimuli consistent with the parametric criteria of habituation. Early evoked potential peak components showed a pattern of intensity generalization of habituation consistent with the predictions of the dual-process theory of habituation. Intensity generalization of late evoked potential peak components occurred in a manner more consistent with the predictions of the stimulus comparator theory of habituation. These results provide further evidence that evoked potentials can be used as electrophysiological indexes of plasticity in humans.     

Arousal and T-maze choice behavior in mice: A convergent paradigm for neophobia constructs and optimal arousal theory

Three experiments investigating the effects of arousal on the T-maze choice behavior of inbred mouse strains are reported. In Experiment 1, CBA and NZB mice were administered unrewarded free choice alternation tests on 10 consecutive days under either No Shock, Shock Start (shocked in the start box), or Shock Choice (shocked at the choice point) treatment conditions. Both strain and treatment effects were observed: In the No-Shock condition, the nonreactive CBA strain alternated, but the reactive NZB strain did not. In the Shock Start condition the CBA strain showed only a suppressed alternation, while the NZB strain administered the same treatment perseverated. Both strains perseverated in the Shock Choice condition. In Experiment 2, NZB mice administered identical shocks in the start box and goal arms on both trials of five consecutive tests conducted once a day perseverated to the same goal arm in which they had been shocked on the first trial. In Experiment 3, NZB mice punished for perseverating (with shock continuation) and simultaneously reinforced for alternating (with shock termination) showed a “punishment paradox”; they perseverated despite the reinforcement contingencies. These results, which are congruent with the optimal arousal theory and several characteristics the theory shares with the emergent neophobia construct, support the contention that arousal mediates a symmetrical relationship between approach and avoidance along a novelty-familiarity continuum.