The effects of intradentate colchicine injections on the performance of tasks requiring spatial working and reference memory are controversial. Multiple‐site colchicine injections (7 μg/μl; via a drawn micropipette) throughout the dentate gyrus (DG) of rats (nine sites in each hemisphere, 0.06 μl 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. Hippocampus 1999;9:668–681. © 1999 Wiley‐Liss, Inc.
The authors examined spatial working memory in the Morris water maze during the activity and rest periods of Wistar 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.
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.
KeywordsOs processos que levam à seleção de certas categorias de informação para processamento preferencial, que caracterizam a atenção, dependem não apenas da história prévia do sistema selecionador, isto é, suas memórias, como também de expectativas geradas com base em memórias sobre regularidades passadas e planos de ação. Defende-se neste trabalho que a associação conceitual envolvendo memória e atenção é vantajosa pois permite oferecer explicações parcimoniosas sobre diversos fenômeros revelados em estudos sobre atenção, além de gerar previsões testáveis sobre os efeitos da experiência prévia no desempenho em testes de atenção. Apresenta-se aqui um modelo sobre a influência de memórias (representadas por vias facilitadas no sistema nervoso) na atividade da rede nervosa e nos processos atencionais durante o desempenho de determinados tipos de tarefas. IntroduçãoMemória corresponde ao processo pelo qual experiências anteriores levam à alteração do comportamento. Atenção corresponde a um conjunto de processos que leva à seleção ou priorização no processamento de certas categorias de informação; isto é, "atenção" é o termo que refere-se aos mecanismos pelos quais se dá tal seleção.O sistema nervoso, em seu processo histórico de interação inicial com o ambiente, reage não apenas a estímulos, mas também às contingências espaciais e temporais entre os estímulos, e também destes com suas respostas, num processo de aprendizagem que leva a modificações no seu funcionamento, caracterizando alterações "de-baixo-para-cima". Com o acúmulo desses registros sobre ocorrências anteriores -memórias no sentido amplo da palavra -e a identificação de regularidades na ocorrên-cia desses eventos, o sistema nervoso passa a gerar previsões (probabilísticas) sobre o ambiente. Então, passa a agir antecipatoriamente e a selecionar as informações que serão processadas -um processo de "cima-para-baixo" -o que confere grande vantagem adaptativa. 1 Uma das conseqüências desse processo é o desenvolvimento de intencionalidade; ou seja, como resultados almejados podem ser previstos com base em registros sobre regularidades passadas, o sistema nervoso pode (1) gerar ações que levem aos resultados desejados e (2) atuar no sentido de selecionar determinados tipos de informação para processamento adicional, isto é, direcionar sua atenção.É indiscutível que esse processo de seleção atencional depende não apenas da história prévia do sistema selecionador, envolvendo suas memórias e portanto o significado pessoal e emocional dos estímulos, mas também de expectativas geradas
Glucose metabolism and insulin signaling disruptions in the brain have been proposed as a likely etiology of Alzheimer's disease. The aim of the present study was to investigate the time course of cognitive impairments induced by intracerebroventricular injection of streptozotocin (STZ) in rats and correlate them with the ensuing neurodegenerative process. Early and late effects of STZ were evaluated by using the reference and working memory versions of the Morris' water maze task and the evaluation of neurodegenerative markers by immunoblotting and the Fluoro-Jade C histochemistry. The results revealed different types of behavioral and neurodegenerative responses, with distinct time courses. We observed an early disruption on the working memory as early as 3h after STZ injections, which was followed by degenerative processes in the hippocampus at 1 and 15 days after STZ injections. Memory disruption increases over time and culminates with significant changes in amyloid-beta peptide and hyperphosphorylated Tau protein levels in distinct brain structures. These findings add information on the Alzheimer's disease-like STZ animal model and on the mechanisms underlying neurodegenerative processes.
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