Biomedical subjects

J Caston

Publications and source records attributed to J Caston.

At least 19 recordsLinked to original sources

PubMed2000

Effects of early midline cerebellar lesion on cognitive and emotional functions in the rat.

Midline lesion of the cerebellum was performed in young 10-day-old DA/HAN strained (pigmented) rats. Once adults, the lesioned animals were subjected to a series of behavioral tests and their performances were compared with those of control (nonlesioned) rats. Compared with controls, the spontaneous motor activity of the lesioned rats was higher, they showed persevering behavior and did not pay attention to environmental distractors. In anxiety and social discrimination tests, disinhibition tendencies were obvious, which suggested that the animals were less dependent on the context. These abnormalities were most likely due to early midline lesion of the cerebellum and not to a deficit in maternal care before weaning, since the dams took care of the lesioned and control pups similarly. From these results, it can be concluded that the cerebellar vermis is involved in motor control, attentional capabilities and emotional behavior. Given that the lesioned rats observed in this study presented obvious autistic-like symptoms, and since a number of autistic subjects have cerebellar deficits and, particularly, a hypoplasia of vermal lobules, our results may strengthen the idea that the cerebellar vermis is involved in autism, as already suggested in the guinea pig (Caston J, et al. Eur J Neurosci 1998;10:2677-2684).

Age Factors↗

PubMed2000

Potentiation of the effect of an anesthetic, chloral hydrate, by stress and corticosterone: a behavioral study in the mouse.

Many studies have demonstrated that stressors can modify the physiological action of drugs, mainly morphine. The present study investigated the effects of a mild stressor on chloral hydrate (Chl)-induced sedation in mice. For 4 consecutive days, NaCl and Chl-treated mice (300 mg kg(-1)) were stressed (S) either by a 5 min exposure to a brightly lit inescapable open field, or i.p. injected with corticosterone (Cor) (15 mg kg(-1)). Then, their spontaneous motor activity was recorded on an actisystem during 20 min and compared with that of the unstressed (US) NaCl and Chl-treated mice. On day 1 and 4, neither stressor nor i.p. administered Cor had any influence on the spontaneous motor activity of NaCl-treated mice. In Chl-treated mice, the spontaneous motor activity was very low. On day 1, it was similar in S mice, Cor-injected mice, and US mice. On the contrary, on day 4, both stress and Cor enhanced the anesthetic-induced hypoactivity, showing that the magnitude of sedation increased. It can then be stated that stressor, provided it was repeatedly administered, potentiated the sedative action of chloral hydrate and that such a potentiation was probably, but not only, Cor-dependent. Given that stress and Chl both produce dopamine overflow, it can be hypothesized that S, potentiates the sedative action of Chl through a dopaminergic link.

Anesthetics, Intravenous↗

PubMed2000

Chronic stress in pregnant rats: effects on growth rate, anxiety and memory capabilities of the offspring.

Female rats were repeatedly stressed for 10 periods of 15 min by the presence of a cat, at the 10th (S10) or the 19th (S19) gestational day. The litter from stressed females often contained a majority of males or a majority of females, especially in the S19 group. The death of pups was dramatically high in the S19 group and, compared with controls, growth of the surviving animals was slower. When adult, their long-term memory was altered and they exhibited an aversive behavior relative to wide areas. Moreover, cognitive alterations were revealed by the low level of exploration and the inability to rapidly process the relevant environmental cues. These deficits resemble those of psychiatric patients who had been submitted to pre-natal stress.

Animals↗

PubMed2000

Effects of centrolateral or medial thalamic lesions on motor coordination and spatial orientation in rats.

The effects of central lateral (CL) or medial thalamic lesions were evaluated on tests requiring balance and equilibrium (rotorod, stationary beam, and hole-board), and spatial orientation (Morris water maze). Lesions of the medial nuclei impaired rotorod and spatial orientation, while CL lesions impaired only rotorod performance. Neither lesion affected stationary beam and hole-board tests or visuomotor guidance while swimming toward a visible platform. These spatial and sensorimotor deficits cannot be explained by reduced cerebral activation, but instead are attributable to specific projections from the anterior intralaminar nuclei to the basal ganglia and neocortex.

Animals↗

PubMed1999

An unsteady platform test for measuring static equilibrium in mice.

An unsteady platform test is presented in which mice must remain still on a narrow surface in order to prevent a fall. The mouse spontaneous mutation, Lurcher, causing cerebellar cortical degeneration, was evaluated on the unsteady platform, requiring balance in a stable body position (static equilibrium), as opposed to the stationary beam test, in which the animals are free to move on a larger surface (dynamic equilibrium). Lurcher mutants spent less time and had a higher number of slips than controls on the unsteady platform. In contrast, Lurcher mutants did not differ from controls for latencies before falling and distance travelled on the stationary beam. These results are discussed in terms of the possible involvement of two cerebellar circuits in motor control.

Animals↗

PubMed1999

Influence of stimulation of the olivocerebellar pathway by harmaline on spatial learning in the rat.

Administration of harmaline to the rat, which activates synchronously and rhythmically the olivary neurons and the olivocerebellar pathway, elicits visuo-motor, spatial learning and spatial memory deficiencies which are dose-dependent. Since activation and lesion of the olivocerebellar pathway have similar effects, it is concluded that normal functioning of this pathway is required for spatial learning achievement.

Analysis of Variance↗

PubMed1999

Role of an enriched environment on the restoration of behavioral deficits in Lurcher mutant mice.

Lurcher mutant mice, characterized by massive degeneration of the cerebellar cortex, and normal littermate controls were reared from birth either in standard conditions or in an enriched environment. The effects of this manipulation on motor functions, landmark water maze learning, exploration, and anxiety were evaluated at 3 months of age. Under standard conditions, Lurcher mutants were impaired in comparison to controls on tests of sensorimotor function and had altered exploratory tendencies. The enriched housing improved the motor coordination of Lurcher mutants and decreased the number of trials before reaching criterion in the landmark water maze. In addition to its effects in Lurcher mutants, enriched rearing also increased some behavioral abilities in normal mice. It is hypothesized that enriched housing altered brain morphology or neurochemistry in both normal and cerebellar-damaged animals.

Animals↗

PubMed1999

Effects of electrolytic lesions of the lateral pallidum on motor coordination, spatial learning, and regional brain variations of cytochrome oxidase activity in rats.

In view of recent theories suggesting a role for basal ganglia circuits in motor control and cognition, rats with bilateral electrolytic lesions of the lateral part of the globus pallidus were compared with control rats on motor coordination tasks and spatial learning in the Morris water maze. By comparison with sham-operated controls, rats with lesions of the lateral pallidum were impaired during acquisition of the rotorod task. Deficits were observed in a wooden beam task, but not in hole-board and suspended string tests. In addition, lesioned rats were impaired during acquisition of place learning but not of visuomotor guidance in the Morris water maze. Alterations of brain metabolism, as assessed by cytochrome oxidase activity, were found in three regions of lesioned rats, the subthalamic nucleus, the superior colliculus, and the centromedial thalamus of lesioned rats, probably as a result of interrupted neocortico-basal ganglia circuitry as a secondary consequence of the primary lesion.

Animals↗

PubMed1999

Rearing environmental enrichment in two inbred strains of mice: 1. Effects on emotional reactivity.

The effects of an enriched rearing environment on two types of anxiety-like behavior (designated "trait" and "state" anxiety) and on spontaneous activity were investigated in two inbred strains of mice, BALB/c (C) and C57BL/6(B6). Subjects were socially reared from birth to 56 days of age under enriched or standard rearing conditions. The enriched environment consisted of an assembly of plastic boxes in which a various number of objects (running wheels, pieces of plastic, etc.) offered the possibility of multiple activities. The subjects were subsequently tested in three situations: a spontaneous activity recorder, an elevated plus-maze test (a model of state anxiety), and a free exploration test (a model of trait anxiety). No group differences could be found in spontaneous activity. Environmental enrichment, however, decreased the level of both types of anxiety-like behavior in the C strain. In contrast, the level of trait anxiety of the B6 mice was not modified. The results were discussed in relation to possible CNS modifications, especially in the limbic system.

Analysis of Variance↗

PubMed1999

Hu-Bcl-2 transgenic mice with supernumerary neurons exhibit timing impairment in a complex motor task.

Programmed neuronal cell death is common during development, and is thought to be important in the elimination of errors in axonal projection, cell position and sculpting of neuronal circuits. However, the potential importance of programmed cell death for complex behaviour in the adult animal has never been addressed. We studied motor abilities in a strain of transgenic mice with neuronal overexpression of the human Bcl-2 protein, which have supernumerary neurons due to reduced developmental cell death. Our results show that these mice have a clear deficiency in fine timing of motor coordination without impairment of basic motor functions. This is the first indication that altered developmental cell death and the consequent neuronal surplus can impair complex behaviour in the adult animal.

Animals↗

PubMed1998

Role of the cerebellum in exploration behavior.

Compared to +/+ mice, Lurcher (+/Lc) mutant mice whose cerebellar cortex is lacking almost all Purkinje cells and granule cells, exhibit a low level of exploration; this deficit is not due to a low level of activity but to both a decreased motivation to explore a novel environment and to spatial deficits. The characteristics of exploration in cerebellectomized +/+ and +/Lc mice suggest that the cerebellum is involved not only in cognitive but also in motivational processes.

Animals↗

PubMed1998

Timed active avoidance learning in lurcher mutant mice.

Lurcher mutant mice (+/Lc) which exhibit a massive loss of neurons in the cerebellar cortex and in the inferior olivary nuclei were subjected to an active avoidance learning task; the animals' avoidance response must occur within a small time window after a short or a long delay. The control mice needed a mean of 8.3 sessions of 10 trials (short delay group) and of 11.8 sessions (long delay group) and showed good retention after a 24 h interval. When subjected to the same number of sessions, the +/Lc mice were unable to learn the timing task. However, a subgroup of lurcher mutants was able to learn after a high number of sessions (25.4 sessions as a mean). There was no intergroup difference in the standard version of one-way active avoidance. These results indicate that the cerebellar cortex is involved in time processing during active avoidance. The cerebellum may be part of a loop including the cerebral cortex known to be involved in time perception. An alternative explanation is that the cerebellar mutant animals had persevering tendencies acquired during performance of the one-way avoidance task.

Animals↗

PubMed1998

Early development of synchronized walking on the rotorod in rats. Effects of training and handling.

There is considerable improvement of motor coordination on the rotorod during the first 3 weeks of development in rats. The purpose of the present study was to determine some factors implicated in this improvement. From days 15-22 of age, rats were: (1) extensively trained on the rotorod; (2) minimally trained on the rotorod; (3) handled daily but not trained on the rotorod; and (4) neither handled nor trained. All animals were tested on the rotorod on day 23, with separate groups of the naive rats also being tested on days, 19, 20, 21 or 22. Latencies before falling and the percentage of time spent walking in time to the movement of the rotating rod were recorded. There was a close correspondence between these two scores during ontogeny. The percentage of time spent walking was similar among extensively trained, minimally trained, and handled rats and significantly higher than that measured in rats tested only on 1 day. These results indicate that the emergence of this postural sensorimotor skill is more dependent on the maturation of sensorimotor brain region than on previous training on the apparatus.

Aging↗

PubMed1998

The cerebellum and postural sensorimotor learning in mice and rats.

Animals with cerebellar damage caused by gene mutations, surgical ablations and irradiation by X-rays during developmental stages are impaired in maintaining posture and equilibrium. For most tests, even in animals with total cerebellectomy, postural sensorimotor learning is not abolished. Simpler compensatory movements may be adopted. The acquisition of simple sensorimotor skills occurring after massive damage of the cerebellar cortex may be explained by the modulatory role of the cerebellar deep nuclei during learning processes or by the influence of extracerebellar regions taking over lost cerebellar function.

Animals↗

PubMed1998

Differential roles of cerebellar cortex and deep cerebellar nuclei in learning and retention of a spatial task: studies in intact and cerebellectomized lurcher mutant mice.

Lurcher mutant mice (+/Lc) exhibit a massive loss of neurons in the cerebellar cortex and the inferior olivary nucleus, while deep cerebellar nuclei are essentially intact. To discriminate the relative participation of the cerebellar cortex and deep structures in learning and memory, 3 to 6-month-old +/Lc mice were subjected to a spatial learning task derived from the Morris water escape. They were able to learn to escape as well as their strain-matched controls (+/+). Seven days later, their scores showed that they had memorized the spatial environment but not as accurately as +/+ mice. Cerebellectomy before training did not significantly alter the escape learning capabilities of either group, whereas cerebellectomy performed after learning completely abolished retention in +/+, as well as in +/Lc, mice. These results suggest that the cerebellum, although not necessary for learning a spatial task, plays a crucial role in its retention, and that the storing structure of spatial information differs in +/+ and +/Lc mice.

Analysis of Variance↗

PubMed1998

An animal model of autism: behavioural studies in the GS guinea-pig.

Autism is a human behavioural pathology marked by major difficulties in abnormal socialization, language comprehension and stereotypic motor patterns. These behavioural abnormalities have been associated with corticocerebral and cerebellar abnormalities in autistic patients, particularly in vermal folia VI and VII. Progress in understanding this disease has been hindered by the absence of a non-primate animal model. GS guinea-pigs are a partially inbred, non-ataxic guinea-pig strain with cerebellar and corticocerebral abnormalities similar to those reported to exist in human patients with autism. In order to determine if GS guinea-pigs represent an animal model of autism, their behaviour was compared with that of Hartley strain guinea-pigs. GS animals learned a motor task significantly more rapidly than Hartley guinea-pigs, but performed it in a more stereotypic manner and were less influenced by environmental stimuli than Hartleys. GS animals exhibited significantly less exploratory behaviour in a novel environment and were significantly less responsive to 50-95 dBA pure tones than Hartley guinea-pigs. In a social interaction assay, GS guinea-pigs interacted significantly less frequently with each other or with Hartley guinea-pigs than Hartleys did under the same conditions. GS behaviour thus exhibits autistic-like behaviour patterns: motor stereotypy, lack of exploration and response to environment and poor social interaction. Coupled with the neuropathological findings, this abnormal behaviour suggests that GS guinea-pigs could be a useful animal model of autism.

Acoustic Stimulation↗

PubMed1997

Fear decrease in transgenic mice overexpressing bcl-2 in neurons.

Neuronal destruction in the amygdala, hypothalamus and cerebellum provokes a diminution in anxiety and neophobia. In transgenic mice that express the human bcl-2 gene under the control of neuron specific enolase promotor (Hu-bcl-2), BCL-2 overexpression reduces the naturally occurring neuronal death, producing an increase of the number of neurons and brain size. Since BCL-2 over-expression has been observed in different parts of the brain and especially in the amygdaloid nuclei, the hypothalamus and the cerebellum, we studied the fear-related behavior of these transgenic mice. Hu-bcl-2 transgenic mice showed a decrease in anxiety and neophobia, indicating that, for this particular behavior, supernumerary neurons elicit the same modification as that observed after neuronal destruction.

Animals↗

PubMed1997

Effect of cerebellar granule cell depletion on spatial learning and memory and in an avoidance conditioning task: studies in postnatally X-irradiated rats.

Rats of the DA/HAN strain (pigmented rats) were submitted to two experimental tasks consisting in spatial learning (water escape experiment) and in passive avoidance conditioning. These rats were either totally or partially deprived of their granule cells using two different schedules of postnatal X-irradiation of the cerebellum. When they were 3 months old, the animals were submitted to an initial learning session, followed by a retrieval test seven days later. The scores of the rats which were partially deprived of granule cells appeared similar to those of controls, except for a mild deficiency of spatial learning. The learning and retrieval scores of the rats totally deprived of granule cells were similar to those of controls at the passive avoidance conditioning task, but these animals were unable to accurately learn a spatial task and showed memory impairments relative to controls. These results are discussed in terms of cognitive defects.

Animals↗