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No / In addition to their role in cellular metabolic activity, thyroid hormones (THs), also regulate neural development; the central nervous system is particularly dependent on TH for normal maturation and function. Specifically, there appears to be extensive inter-reliance between TH and acetylcholine (Ach), nerve growth factor and hippocampal function. These associations led us to investigate the possible effects of thyroxine (L-T4) on performance of a spatial learning task, where cholinergic activity and hippocampal function are known to be important. Groups of rats (n=20) received saline (controls) or L-T4 at 2.5 or 5 mg/kg daily for 4 days as a sub-chronic treatment, or 0, 5 or 10 mg/kg doses administered every third day for 28 days prior to testing as a chronic regimen. Rats were assessed in a watermaze for their ability to find a submerged or visible platform. Forty minutes prior to watermaze testing, half the animals in each group received 1 mg/kg scopolamine to elicit a cognitive deficit. Following testing, rats were decapitated, blood samples taken, and the frontal cortex and hippocampus were dissected out for acetylcholinesterase (AChE) assay. The results showed that L-T4 treatment, administered both sub-chronically and chronically, significantly enhanced the ability of rats to learn a spatial memory task, compared with controls. Moreover, both short-term and long-term L-T4 treatment reduced the cognitive-impairing effects of scopolamine. Improvements in performance were shown to occur alongside significantly increased cholinergic activity in frontal cortex and in the hippocampus of treated animals.These findings demonstrate an augmentative effect of L-T4 upon cognitive function, possibly mediated by an enhancement of cholinergic activity. The results support previous findings of a relationship between L-T4 and acetylcholine, and underscore possible mechanisms by which disorders of thyroid function may be associated with cognitive decline.

Cognitive Map Theory (O’Keefe & Nadel, 1978) posits that spatial behavior can reflect locale or taxon strategies. Only locale strategies depend on cognitive maps, and learning recruited by these strategies is unlike associative learning (e.g., Rescorla & Wagner, 1972; Mackintosh, 1975), which is prevalent in the taxon system. Associative learning phenomena like the blocking effect (Kamin, 1969) should therefore not occur during acquisition of cognitive maps. Contrary to this prediction, blocking effects have been demonstrated in spatial learning (e.g., Biegler & Morris, 1999; Chamizo, Sterio, & Mackintosh, 1985; Hamilton & Sutherland, 1999), and have been generally interpreted as evidence against cognitive map theory. Here we provide evidence suggesting that taxon and not locale strategies were promoted in these experiments, and we ask which factors determine whether taxon or locale strategies control spatial behavior in a computer-implementation of a widely used spatial task (Morris Water Maze; Morris, 1981). We isolated two factors relevant for spatial strategy choice in human spatial learning that are both related to the individual’s preexisting knowledge, namely conceptual knowledge about the distal cues, and knowledge about the task affordances. The blocking effect was used as an index for locale or taxon learning. We found that taxon strategies were more likely for abstract distal cues, while concrete cues promoted locale strategies – blocking was present for the former, but not the latter. When subjects were aware that the distal cues predicted locations, locale, and not taxon strategies were recruited, such that blocking was not observed. Spatial strategy choice appears to be largely driven by interindividual differences, and can therefore not be easily predicted a priori. Our findings cannot be explained by associative learning theories, but provide strong support for cognitive map theory and the position that multiple behavioral systems exist in the brain.

A neurogênese hipocampal é modulada por muitos fatores que incluem envelhecimento, estresse, enriquecimento ambiental, atividade física e aprendizado. Atividade física voluntária (espontânea) estimula a proliferação celular no giro denteado e facilita a aquisição e/ou retenção de tarefas dependentes do hipocampo, incluindo o Labirinto Aquático de Morris. Embora seja bem estabelecido que o exercício físico regular melhore o desempenho em tarefas de memória e aprendizado, não está claro qual a duração desses benefícios após o final da atividade física. Neste estudo investigamos a relação temporal entre os efeitos benéficos da atividade física associado ao aprendizado de tarefa dependente da função hipocampal, e sua relação com a neurogênese, levando em consideração também o tempo decorrido desde o término da atividade física. Grupos independentes de ratos tiveram acesso a roda de atividade ao longo de 7 dias (Grupo EXE) ou roda bloqueada (Grupo Ñ-EXE) e receberam injeções de BrdU nos últimos 3 dias de exposição roda. Após um INTERVALO de 1, 3 ou 6 semanas após o final da exposição a roda de atividade após o final da exposição a roda de atividade, os animais foram testados no labirinto aquático de Morris, sendo uma parte deles expostos a tarefa de memória operacional espacial, dependente da função hipocampal (H), e outra parte a uma tarefa de busca por uma plataforma visível, independente da função hipocampal (ÑH). Em ambos os casos, o intervalo entre as tentativas (ITI) foi de 10 minutos durante as sessões 1-6 e (virtualmente) zero minutos durante as sessões 7-10. Concluída a tarefa os cérebros foram processados para imuno-histoquímica. Foram feitas imunoistoquímicas para a detecção de Ki-67 (proliferação celular), BrdU, NeuN (para identificar neurónios maduros), e DCX (para identificar imaturo neurônios). Nossos dados suportam a ideia que atividade física voluntária induz um aumento na proliferação celular e na diferenciação neuronal (neurogênese) no giro denteado. A introdução de um período de intervalo entre o final do exercício e a execução da tarefa comportamental causa uma redução significativa na sobrevivência dos novos neurônios, como observado com 1 semana de intervalo em comparação com os animais testados com 6 semanas de intervalo. Em contraste, entretanto, o presente resultado não confirma que esse aumento da neurogênese é acompanhado por melhora na memória espacial, como avaliado por meio da versão que envolve memória operacional no labirinto aquático de Morris. O aprendizado da tarefa do labirinto aquático de Morris, na versão de memória operacional que é dependente do hipocampo, leva a um aumento da sobrevivência dos novos neurônios que foram produzidos no período de exercício, ao passo que o aprendizado da versão independente da tarefa leva a uma redução do número absoluto de novos neurônios / Hippocampal adult neurogenesis is modulated by many factors including age, stress, environmental enrichment, physical exercise and learning. Spontaneous exercise in a running wheel stimulates cell proliferation in the adult dentate gyrus and facilitates acquisition and/or retention of hippocampal-dependent tasks including the Morris water maze. While it is well established that regular physical exercise improves cognitive performance, it is unclear for how long these benefits last after its interruption. In this study, we investigate the temporal relation between exercise-induced benefits associated with learning of a hippocampal-dependent task, this relationship with neurogenesis, considering the time after exercise has ended. Independent groups of rats were given free access to either unlocked (EXE Group) or locked (No-EXE Group) running wheels for 7 days, having received daily injections of BrdU for the last 3 days. The animals were then transferred to standard home cages. After a time period of either 1, 3 or 6 weeks, the animals were tested in the Morris water maze, one of them being exposed to the spatial working memory task dependent on hippocampal function (H) and partly to a task search for a visible platform, independent of hippocampal function (NH). In both cases, the interval between trials (ITI) was 10 minutes during sessions and 1-6 and (virtually) zero minute during the sessions 7-10. After the task brains were processed for immunohistochemistry. Cell proliferation and net neurogenesis were assessed in hippocampal sections using antibodies against BrdU, NeuN (to identify mature neurons), and DCX (to identify immature neurons). Data of the present study confirm that exposure of rats to 7 days of spontaneous wheel running increases cell proliferation and neurogenesis. In contrast, however, the present results did not confirm that this neurogenesis is accompanied by a significant improvement in spatial learning, as evaluated using the working memory version of the Morris’ water maze task. The introduction of a delay period between the end of exercise and cognitive training on the Morris water maze reduces cell survival; the number of new neurons was higher in the EXE1 week delay group as compared to the EXE6 week delay. We showed that learning the Morris water maze in the working memory task dependent on hippocampal function (H) increases the new neurons survival, in contrast, learning hippocampal-independent version of the task decreases number of new neurons

Prenatal stress exposure (PNS) has detrimental effects on the offspring’s brain and behaviour and has been identified as an etiological factor in inducing cognitive function deficits in rodents and humans. The neural mechanisms are unclear, however reprogramming of the neuroendocrine stress axis, the hypothalamo-pituitary- adrenal (HPA) axis is hypothesised. A psychosocial stressor (residentintruder paradigm) was used to generate PNS rat offspring, making these studies clinically compatible. The hippocampus and the medial prefrontal cortex (mPFC) are critical in regulating cognitive function and also contribute to the negative feedback control of the HPA axis via corticosteroid receptors, including the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR). Here the Barnes maze was used to assess spatial learning and memory in male and female PNS offspring during adulthood under different scenarios, including basal and acute and chronic stress conditions. Under basal conditions, PNS was associated with reduced GR and MR mRNA expression in the medial prefrontal cortex (mPFC) and the hippocampus, respectively; suggesting inhibitory feedback control of the HPA axis may be compromised in PNS rats. Moreover, impaired spatial learning was observed in male PNS rats following acute restraint stress. Bilateral lesions of the prelimbic cortex and central administration of an MR antagonist in control rats suggested acute stress-induced learning deficits in PNS males were a result of impaired hippocampus-mediated inhibitory feedback control of the HPA axis. Conversely, a one-week variable stress regimen facilitated spatial learning in PNS rats and this was associated with elevated MR mRNA expression in the dentate gyrus. Moreover, facilitated learning in the PNS rats exposed to chronic stress could be blocked by central administration of an MR antagonist, indicating a facilitatory role of hippocampal MR in spatial learning. In summary, opposite effects of PNS on spatial learning were observed under acute and chronic stress conditions, in which hippocampal MR played a key role in regulating behavioural performance. The effect of age was also examined in PNS rats, and the findings from middle-aged (10-11 months old) rats indicated PNS may accelerate cognitive decline. Sex differences were also studied, with control females’ out-performing males under basal conditions in terms of spatial learning and behavioural flexibility; however following prenatal or chronic stress these sex differences were no longer detected. Furthermore, acute stress impaired spatial learning to a greater extent in females, and this might be attributed to greater HPA axis responses to stress in females compared with males. In conclusion, prenatal stress alters later cognitive performance, in a sex- and stress context-dependent manner. Hippocampal MR plays a critical role in mediating spatial learning, particularly during stress conditions.

Despite very extensive studies on molecular mechanisms of learning and memory formation it is little known about individual variation in the learning skills within a random animal population and about the differences in the brain biochemistry behind this variation. In the present study, we have focused on the expression and distribution of nitric oxide synthase (NOS), one of the molecules implemented in activity-dependent neuroplasticity, in the rat hippocampus, the structure critical for episodic memory in humans and animals. The aim of the present study was to investigate the differences in expression of three different NOS isoforms: neural (n), epithelial (e), and inducible (i), in four hippocampal subregions (CA1, CA3, DG, and hilus) between Wistar rats classified on the basis of their performance in partially baited 12-arm radial maze as &ldquo / good&rdquo / and &ldquo / poor&rdquo / learners. The NOS isoforms were visualized on coronal hippocampal sections using fluorescent immunohistochemistry technique and n- and eNOS images were processed using ImageJ software, while iNOS immunoreactivity (IR) was assessed by counting immunoreactive cells. In this study, overall hippocampal levels of nNOS were significantly higher than those of eNOS and iNOS. The level of n and eNOS was higher in CA1 compared to DG/hilus areas, but lower than that in CA3 region. The expression of iNOS was the highest in CA1 and the lowest in hilus region. nNOS IR was significantly higher in &ldquo / poor&rdquo / than in &ldquo / good&rdquo / learners but only in CA1 region. No significant between-group differences were found in eNOS expression. iNOS expression was higher in &ldquo / poor&rdquo / learners but it did not reach the required significance level.

The aim of the present study was to elucidate the possible relationship between the levels of various brain fatty acids and learning indices in aged and young mice classified as &ldquo / good&rdquo / or &ldquo / poor&rdquo / learners basing on their performance in a spatial learning task, the Morris Water Maze. The levels of several fatty acids including palmitic, stearic, oleic, linoleic, arachidonic acid (AA) and docosahexaenoic acid (DHA) were measured using gas chromatography separately in samples from four different brain areas: hippocampus, cortex, striatum and hypothalamus. The level of oleic acid in the cerebral cortex was significantly higher in young-good learners as compared to young-poor learners and higher in young-poor learners than in old-poor learners, with no significant difference in the concentration of this acid between old-good and old-poor learners. The most consistent correlation between animals&rsquo / learning capacity and brain fatty acid&rsquo / level was found for the arachidonic acid in the hippocampal region: AA level was significantly lower in young-good learners as compared to both young-poor learners&rdquo / and old-good learners&rdquo / with young-good learners showing significantly better performance than the two other groups. Interestingly, except hypothalamus, no significant between-group differences were recorded for the remaining fatty acids including DHA, in none of the four brain regions examined.

No description available.

The objective of the present study was to examine the effects of prenatal exposure to alcohol on sensorimotor coordination, emotionality, learning and memory in young adult Wistar rats. Most of the recent reports concerning behavioral effects of fetal alcohol exposure refer to the juvenile period of life and very few studies investigated different aspects of behavior simultaneously in the same subjects. In the current study, alcohol was delivered to the pregnant dams by intragastric infusions, throughout gestation days (GD) 7-20, at the dose of 6g /kg maternal body weight /day. This dose resulted in relatively high peak blood alcohol concentration (340 mg/dl) as assessed on GD 20. A pair-fed isocaloric and untreated control groups were included. Prenatal alcohol administration retarded dams&rsquo / weight gain significantly, and had an adverse effect on pups&rsquo / weight at birth but not in adulthood. No between-group differences were observed in the litter size and in the pups&rsquo / mortality. The adult brain weight was neither affected. Pups were subjected to a series of behavioural tests as young adults (at 2.5 months of age). In adulthood, rats prenatally treated with alcohol were not impaired in sensorimotor coordination and/or did not show muscle weakness as assessed by rotarod/accelerod tests. Their behavior in the open field and plus maze suggested alcohol-induced increase in iv anxiety level and some decrease in behavioral flexibility, but hyperactivity was not observed. In cognitive tasks, alcohol treated rats showed slightly slower rate of initial place learning in the water maze. However, memory retention tested after 1 and 10-day delay, reversal learning, rate of extinction of place preference, as well as working memory capacity appeared to be the same in alcohol exposed and control rats. The possible reasons of this negative result are discussed.