Gilberto Fernando Xavier

Effect of Circadian Phase on Performance of Rats in the Morris Water Maze Task

The authors examined spatial working memory in the Morris water maze during the activity and rest periods ofWistar rats. Wheel-running activity was measured continuously as a marker of circadian phase. To minimize possible masking effects on performance, animals were placed in constant dim light the day before testing and tested in similar light conditions. Three experiments were run, each of them using animals varying in their previous experience in the water maze. Half of the animals of each experiment were tested 2 to 3 h after activity onset (active group), and the other half were tested 14 to 15 h after activity onset (inactive group). In the three experiments, a significant phase effect was observed in the animals’ performance in the water maze; animals tested in the active phase showed steeper acquisition curves. These phase effects on performance are due to the animals’ search pattern and not to a better acquisition and maintenance of spatial information; rats tested in the inactive phase found the platform faster on the first trial of the test, when the information on the location of the platform had not been presented to the animals. This effect vanished as the amount of training in the pool increased. Finally, swimming speed also showed a temporal effect, suggesting the existence of a phase effect for motivation to escape from the water; rats tested during their inactive phase tended to swim faster. All together, the data suggest a modulating effect of the biological clock on performance in the water maze, particularly when the animals are less experienced.

A construção da atenção a partir da memória

The processes that lead to the selection of information for additional processing, which characterizes attention, depend upon previous experiences and expectancies generated in the light of stored past experiences regularities and plans for action. It is proposed that conceptual association between memory and attention brings advantages for explaining a diversity of attentional phenomena and allow to generate testable predictions relating past experiences and performance in tests for attention. A model is presented relating the trained neural network (memories) and attention during performance of behavioral tasks.

Contextual, but not auditory, fear conditioning is disrupted by neurotoxic selective lesion of the basal nucleus of amygdala in rats

The basolateral amygdala complex (BLA) is involved in acquisition of contextual and auditory fear conditioning. However, the BLA is not a single structure but comprises a group of nuclei, including the lateral (LA), basal (BA) and accessory basal (AB) nuclei. While it is consensual that the LA is critical for auditory fear conditioning, there is controversy on the participation of the BA in fear conditioning. Hodological and neurophysiological findings suggest that each of these nuclei processes distinct information in parallel; the BA would deal with polymodal or contextual representations, and the LA would process unimodal or elemental representations. Thus, it seems plausible to hypothesize that the BA is required for contextual, but not auditory, fear conditioning. This hypothesis was evaluated in Wistar rats submitted to multiple-site ibotenate-induced damage restricted to the BA and then exposed to a concurrent contextual and auditory fear conditioning training followed by separated contextual and auditory conditioning testing. Differing from electrolytic lesion and lidocaine inactivation, this surgical approach does not disturb fibers of passage originating in other brain areas, restricting damage to the aimed nucleus. Relative to the sham-operated controls, rats with selective damage to the BA exhibited disruption of performance in the contextual, but not the auditory, component of the task. Thus, while the BA seems required for contextual fear conditioning, it is not critical for both an auditory-US association, nor for the expression of the freezing response.

Dentate gyrus and spatial behaviour

This article reviews evidence from studies employing colchicine-induced granule cell loss in the adult rat brain, and irradiation-induced hypoplasia of the neonatal dentate gyrus, on the performance of spatial and non-spatial behavioral tasks. The general picture emerging from this analysis reveals that the dentate gyrus granule cells are critically involved in spatial behavior, particularly when this requires the adoption of place strategies. This notion also provides an explanation for the behavioral effects of dentate gyrus granule cell loss seen in apparently non-spatial tasks.

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.

A modularidade da memória e o sistema nervoso

Memory seems not to be a single entity but a pool of several abilities mediated by distinct brain systems. Examination of available evidence allows distinction between short-term memory, working memory and long-term memory. Besides the existing task division into modules, which involves several processing units working in parallel, the final result is a unitary memory experience. Each module of memory maintains extensive connections with the others, and variable levels of independence between them are maintained. Lesions of independent modules break up their function, while lesions in modules which cooperate intimately produce an alteration of functioning in the unaffected ones in order to minimize deficiencies. This independent but cooperative functioning of modules can explain experimental dissociations after lesioning, and also the unitary memory experience in normal subjects. Data on lesioning of neural circuits that underly some modules of memory are analysed.

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.

Temporal lobe epilepsy and social behavior: An animal model for autism?

Social behavior depends on the integrity of social brain circuitry. The temporal lobe is an important part of the social brain, and manifests morphological and functional alterations in autism spectrum disorders (ASD). Rats with temporal lobe epilepsy (TLE), induced with pilocarpine, were subjected to a social discrimination test that has been used to investigate potential animal models of ASD, and the results were compared with those for the control group. Rats with TLE exhibited fewer social behaviors than controls. No differences were observed in nonsocial behavior between groups. The results suggest an important role for the temporal lobe in regulating social behaviors. This animal model might be used to explore some questions about ASD pathophysiology.

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.

Exposure of Neonatal Mice to Tobacco Smoke Disturbs Synaptic Proteins and Spatial Learning and Memory from Late Infancy to Early Adulthood

Exposure to environmental tobacco smoke (ETS) in the early postnatal period has been associated with several diseases; however, little is known about the brain effects of ETS exposure during this critical developmental period or the long-term consequences of this exposure. This study investigated the effects of the early postnatal ETS exposure on both reference and working memory, synaptic proteins and BDNF from late infancy to early adulthood (P3-P73). BALB/c mice were exposed to ETS generated from 3R4F reference research cigarettes (0.73 mg of nicotine/cigarette) from P3 to P14. Spatial reference and working memory were evaluated in the Morris water maze during infancy (P20-P29), adolescence (P37-P42) and adulthood (P67-P72). Synapsin, synaptophysin, PSD95 and brain-derived neurotrophic factor (BDNF) were assessed at P15, P35 and P65 by immunohistochemistry and immunoblotting. Mice that were exposed to ETS during the early postnatal period showed poorer performance in the spatial reference memory task. Specifically, the ETS-exposed mice exhibited a significantly reduced time and distance traveled in the target quadrant and in the platform location area than the controls at all ages evaluated. In the spatial working memory task, ETS disrupted the maintenance but not the acquisition of the critical spatial information in both infancy and adolescence. ETS also induced changes in synaptic components, including decreases in synapsin, synaptophysin, PSD95 and BDNF levels in the hippocampus. Exposure to ETS in the early postnatal period disrupts both spatial reference and working memory; these results may be related to changes in synaptogenesis in the hippocampus. Importantly, most of these effects were not reversed even after a long exposure-free period.