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Biomedical subjects

G F Xavier

Publications and source records attributed to G F Xavier.

8 recordsLinked to original sources

Dentate gyrus-selective colchicine lesion and disruption of performance in spatial tasks: difficulties in "place strategy" because of a lack of flexibility in the use of environmental cues?

The effects of intradentate colchicine injections on the performance of tasks requiring spatial working and reference memory are controversial. Multiple-site colchicine injections (7 microg/microl; via a drawn micropipette) throughout the dentate gyrus (DG) of rats (nine sites in each hemisphere, 0.06 microl at each site) selectively destroy about 90% of the DG granule cells, as revealed by quantitative stereological estimates; stereology also revealed minor neuronal losses in the CA4 (33%) and CA1 (23%) subfields, but lack of damage to the CA3 hippocampal subfield. Spatial reference and working memory were assessed in Morris' water maze; in the reference memory task, the rats were required to learn a single, fixed location for the platform over several days of training; in the working memory task, animals were required to learn a new platform location every day, in a matching-to-place procedure. Compared to sham-operated controls, lesioned rats showed significant disruption in acquisition of the reference memory water maze task; however, the data reveal that these rats did acquire relevant information about the task, probably based on guidance and orientation strategies. In a subsequent probe test, with the platform removed, lesioned rats showed disruption in precise indexes of spatial memory (e.g., driving search towards the surroundings of the former platform location), but not in less precise indexes of spatial location. Finally, the lesioned rats showed no improvement in the match-to-place procedure, suggesting that their working memory for places was disrupted. Thus, although capable of acquiring relevant information about the task, possibly through guidance and/or orientation strategies, DG-lesioned rats exhibit a marked difficulty in place strategies. This is particularly evident when these rats are required to deal with one-trial place learning in a familiar environment, such as in the working memory version of the water maze task, which requires flexibility in the use of previously acquired information.

Animals↗

Loss of CA1 cells following global ischaemia correlates with spatial deficits in the circular platform task.

The effect of 15 min, four-vessel-occlusion (4-VO) ischaemia on performance by rats in the circular platform task (CPT) was investigated. Possible correlations between the extent of hippocampal cell loss and behavioural disruption were evaluated. Sham-operated controls (n=10) and 4-VO ischaemic animals (n=32) were required to escape from a 1.2 m diameter, brightly illuminated, white surface into a dark goal box located under one of 18 equally-spaced, 9 cm diameter holes arranged around the circumference (3 trials per day). The goal box was maintained in a single, fixed, rewarded location relative to the extramaze cues for 7 days (days 16-22 post-ischaemia). During the reversal test, the goal box was transferred to a new location 140 degrees from the initial point and kept in this new position from day 23 through day 25 post-ischaemia. Ischaemic rats were slower to find the goal box than sham-operated controls; this learning deficit correlated with the degree of neuronal loss in the CA1, but not in the CA2, CA3 and CA4 subfields and presubiculum of the hippocampal formation. During the reversal test, ischaemic rats persisted in searching for the goal box at the initially rewarded location. The circular platform task provides a good model for behavioural studies following transient forebrain ischaemia in the rat.

Animals↗

Hippocampal lesions induced by ionizing radiation: a parametric study.

The selective lesion of granule cell populations in the dentate gyrus induced by ionizing radiation has been proposed as a useful method for evaluating the effects of hippocampal lesions on behavioral tasks. In the first part of the present study we confirmed the induction of the selective lesion of hippocampal dentate gyrus by ionizing radiation in infant Wistar rats, reported previously, but to a smaller extent with less cell loss. A parametric study was thus performed to assess the effect of modification of the parameters previously tested, comprising three further steps: an increase in the total dose of X-rays and modification of the fractionating schedule; use of three radiation types, X-ray, gamma-ray, and electrons (at two energy levels, 3 and 7 mev); use of three X-ray energy levels, 180, 200 and 250 kVp; and assessment of the effect of five total X-ray doses, at 200 kVp, 10, 14, 16, 18 and 20 gy (grays). The data suggests that X-ray radiation, in a total dose of 14 gy, at the 200 kVp energy level, fractionated into seven consecutive exposures of 2 gy each and produces a lesion of about 85% of the dentate gyrus granule cells.

Animals↗

Rats do react to stimulus omission.

1. The great majority of data supporting the hypothesis of a system capable of comparing current sensorial inputs with an internal representation of the environment comes from studies about exploratory activity to new stimuli or to manipulation of features of a familiar stimulus. On the other hand, these data could also be explained simply by arousal constructs. In this context, demonstrations of exploratory behavior to the absence of a previously presented stimulus (i.e., stimulus omission) would provide stronger support for the idea of a comparator. 2. To test the reaction of rats to the absence of a stimulus, rats were submitted to 7 exploratory trials in an open-field. In the 1st trial there were only two patterns on the apparatus wall. In trials 2-6 a stimulus was presented in a designated area of the field. Finally, in the 7th trial this stimulus was omitted. Results showed that the animals reacted to the stimulus omission by spending more time in the stimulus presentation place during the 7th trial than 1) in the 1st trial (also without stimulus), 2) in the 6th trial (last trial with a stimulus present), and 3) in 3 neutral sectors of the same size as the stimulus presentation place, during the 7th trial. 3. These data indicate that rats do react to the absence of a familiar stimulus and provide strong support for the existence of a Comparator System since the rats responded to "something that wasn't there anymore", a response that could only be due to a reaction triggered by a mismatch between internal representation of the environment and its present state.

Analysis of Variance↗

Rats with dorsal hippocampal lesions do react to new stimuli but not to spatial changes of known stimuli.

The effect of visual distracting stimuli upon the straight alleyway performance of dorsal hippocampectomized Wistar rats was investigated. In comparison with control animals it was observed that dorsal hippocampectomized animals (1) ambulated more during the preexposure phase, (2) acquired at the same rate a running response for food (training phase), (3) reacted similarly to a new visual stimulus (black cards) presented in a sector of the alleyway, and (4) habituated to successive presentations of that stimulus in the same place. (5) However, dorsal hippocampectomized rats did not react, unlike the controls, to the presentation of the same stimulus in another place of the alleyway but (6) reacted to the visual pattern change of the stimulus (now black/white check cards) in the same place. These results indicate that under certain experimental conditions, hippocampus-lesioned animals are capable of interrupting a running response for food in order to explore a new conspicuously located stimulus, habituate to repeated presentations of that stimulus, and to react to a new pattern of visual stimulation. They suggest that hippocampectomized rats do not lose the capacity to react to a new stimulus; the disruption seems to be related to the spatial context of stimulus presentation, supporting a spatial mapping hypothesis of hippocampal function.

Animals↗

On delay-of-punishment and preexposure time: effects on passive avoidance behavior in rats.

Some procedures commonly employed in testing hypotheses of instrumental learning and classical conditioning as applied to the step-through passive avoidance task in rats are examined. In Experiment I, a 'delay-of-punishment gradient', i.e., decreased passive avoidance performance, was obtained by increasing response-shock time intervals (from 0 to 600 s) in training sessions. In Experiment II, decreased passive avoidance behavior was also obtained by submitting animals to nonreinforced preexposure (0 to 600 s) in the shock compartment prior to their receiving shock contingent on the response in training sessions. Experiment III repeated the 'delay-of-punishment gradient' and showed that adequate nonreinforced preexposure time before training decreases passive avoidance performance in animals trained through a noncontingent procedure. The results clearly show that environment training preexposure has a decreasing effect on passive avoidance performance. Increasing response-shock interval also has a decremental effect on this task. With large time intervals the latter effect can be explained as the result of preexposure to the training environment; the possibility of interaction between both processes was not discarded. For smaller time ranges (up to 30 s), the usual interpretation of 'delay-of-punishment gradient', namely decreased response-shock association, seems to be adequate to account for the results.

Animals↗

Effects of housing conditions on three behavioral tests in rats.

Groups of rats housed since weaning under two different kinds of housing conditions (wire and wooden cages) were compared at adulthood in the open field test, the step-through passive avoidance test, and for aggressiveness induced by REM-sleep deprivation and apomorphine administration. In the open field test wire-caged rats showed less rearing and grooming than wood-caged rats. This difference was accentuated by a single previous electrical shock (i.e., wire-caged rats exhibited less ambulation, rearing and grooming and more defecation than wood-caged rats, after shock) and was not altered by prior habituation to handling. In the passive avoidance test there were no significant differences between wire- and wood-caged rats. Wire-caged rats were more aggressive than wood-caged rats after REM-sleep deprivation and the administration of apomorphine. These results show that the control of previous housing conditions is an important variable to be considered in behavioral studies.

Aggression↗

Induction of microglial immunomolecules by anterogradely degenerating mossy fibres in the rat hippocampal formation.

Degeneration of myelinated axonal connections is generally held to provide a strong stimulus for microglial expression of major histocompatibility complex (MHC) class II antigen. The present study demonstrates that strong microglial reactions also are induced by axonal and terminal degeneration of the unmyelinated hippocampal mossy fibres. After destruction of dentate granule cells by focal injections of colchicine (or transection of the mossy fibres) in adult rats, immunocytochemical analysis of the mossy fibre terminal fields in the dentate hilus and regio inferior of hippocampus proper (CA3) revealed profound changes in microglial cells with increased expression of the complement receptor type 3 and induction of MHC class I antigen, leukocyte common antigen, lymphocyte function-associated antigen-1 and MHC class II antigen. The microglial reaction, first detectable 4 days after the lesion, became maximal during the third postlesional week, and had almost vanished 6 weeks after the lesion. From recent studies we know that anterograde degeneration of myelinated Schaffer-collaterals from CA3 to regio superior of hippocampus proper and myelinated entorhinal perforant path fibres to fascia dentata is accompanied by microglial expression of MHC class I antigen, but not class II. Together with the present findings, this demonstrates that myelin debris is neither necessary nor sufficient to induce expression of microglial MHC class II antigen within the hippocampus.

Animals↗