The main goal of this study was to further explore the hypothesis that experience-dependent neural network activity and neurotransmission can modulate adult OPC proliferation and differentiation. More specifically, we used stereology to establish whether extensive reference memory training and system-wide administration of GABAergic agonists and antagonists could influence the proliferation and differentiation of adult OPCs, as well as the prevalence of OPC-neuron pairs. Analysis of the effects of reference memory training on OPC proliferation and differentiation corresponds to experiment 2, analysis of the effects of GABAergic agents on OPC proliferation and differentiation corresponds to experiment 3, and analysis of the effects of both reference memory training and GABAergic agents on OPC-neuron pairs, as well as an histological analysis of these closely apposed cells, corresponds to experiment 4.

Lithium is widely used in the management of bipolar disorder, yet memory impairment is a serious side effect. To assess the effects of lithium on spatial working and reference memories, we have employed a plus maze utilizing spontaneous alternation (SA) and place-learning paradigms in two experiments with the black molly fish. Four treatment groups were gavaged with 20 μl of a 10, 100, or 1000 mM lithium chloride (LiCl) solution or ddH2O vehicle every 12 h for 22 to 24 days. On Day 15, subjects began an 8-day SA task or a 10-day place-learning task. Results indicate that there is a significant difference in SA performance among the treatment groups for Days 1, 2, and 3. Results of the place-learning task indicate that the 1 M dose group needed significantly more trials to reach criterion and made significantly fewer correct first choices than the other dose groups. Capillary ion analysis determinations of plasma and brain lithium levels illustrate linear dose-response relationships to doses administered. Regression analyses indicate that there is a relationship between SA performance and plasma/brain lithium levels during the initial part of testing. Collectively, the results indicate that chronic lithium administration impairs spatial working and reference memories.

No description available.

There is a growing consensus, based on several converging lines of evidence, which suggests schizophrenia is the product of a developmental insult occurring in the late 2 nd or early 3 rd trimester. Additionally, it has been observed that adults who abuse the noncompetitive NMDA antagonist PCP present with symptoms that mimic schizophrenia, such as hallucinations, formal thought disorder, delusions, unstable or flattened affect, social withdrawal, and impaired cognition. Thus, several labs have attempted to use early postnatal PCP administration in rodents as a drug model of schizophrenia. The current study investigated the cognitive effects of early postnatal PCP administration in C57BL/6 mice. Mouse pups received daily administrations of either 10.0 mg/kg PCP or saline on postnatal (PN) days 5-15. After weaning, pups were assessed in locomotor activity, a reference memory task in the Morris water maze, and a spatial delayed alternation task in the T-maze. Additionally, pups were subjected to a pharmacological challenge with PCP in the delayed alternation task. In males, No significant differences were detected between PCP- and saline-treated animals in locomotor activity. However, in the reference memory task, PCP-treated males had significantly longer path lengths, and displayed a non-significant trend towards increased thigmotaxia. Furthermore, males treated with PCP displayed significantly reduced accuracy in the working memory task without differences in choice latency, and were more sensitive to the acute effects of PCP than saline controls. Finally, these deficits were associated with a 29% increase in NR1 subunit expression in the hippocampus. Interestingly, PCP-treated female mice were not significantly different from saline-treated controls in locomotor activity, reference memory task performance, or delayed alternation performance, did not have a significantly different reaction to pharmacological challenge with PCP in the delayed alternation task, and did not demonstrate any changes in NR1 subunit expression. The present study provided the first evidence that early postnatal PCP administration in C57BL/6 mice can produce selective memory pairments. However, this effect was limited to the male mice, suggesting that the female mice were protected somewhat from these effects.

Depuis de nombreuses années, les scientifiques ont étudié les bases neurales de la mémoire. Cependant, une question clé demeure: comment le cerveau distingue t'il les informations suffisamment importantes pour être consolidées en mémoire à long terme des informations stockées de manière temporaire en mémoire à court-terme/mémoire de travail, et qui doivent être effacées afin de ne pas saturer nos ressources cognitives. Contrairement à l'opinion populaire qui considère l'oubli comme nuisible à notre mémoire, de nombreux travaux suggèrent que l'oubli est un processus adaptatif essentiel permettant le filtrage des informations non-essentielles qu'on peut stocker de manière temporaire. Étonnamment, on connaît peu de choses des bases cellulaires et moléculaires de cet oubli adaptatif. Le travail présenté dans cette thèse vise à déterminer les bases de cette forme d'oubli adaptatif, en particulier de celui nécessaire au traitement des informations en mémoire de travail. Avec cette thèse, nous avons ainsi montré que le gyrus denté est une structure clé responsable du traitement des informations non pertinentes en mémoire, un processus essentiel qui permet une utilisation optimale de nos ressources cognitives. Nous pensons que ces travaux nous aident à mieux comprendre comment le cerveau gère les interférences, mais également à identifier les mécanismes responsables de l'oubli « utile » d'informations / For many years, scientists have been investigating the neural bases of memory. However, a key question remains unanswered: how does the brain distinguish information important enough to be consolidated into long-term memory from information required only temporarily, and that needs to be cleared away for not saturating our cognitive resources. In contrast to the popular view considering forgetting as deleterious to our ability to remember, forgetting might be an essential adaptive process allowing the filtering of non-essential information. Surprisingly, very little is known on the cellular and molecular bases of adaptive forgetting. The work presented in this thesis aims to find a way to determine such bases of adaptive forgetting, in particular in the context of Working Memory processing. With this thesis, we thus showed that the dentate gyrus is a critical node in processing the forgetting of irrelevant information, an essential process allowing optimal use of cognitive resources. Our work sheds light not only on the question of how the brain responds to interferences, but also on the mechanisms of "forgetting" what should be forgotten

No description available.

La maladie d'Alzheimer (MA) est caractérisée par un déclin progressif des fonctions cognitives avec une détérioration de la mémoire, une atrophie cérébrale et deux lésions histologiques caractéristiques retrouvées lors d'examens post-mortem : les plaques extracellulaires de peptide β-amyloïde et les enchevêtrements intracellulaires de la protéine Tau anormalement phosphorylée. De nombreux modèles animaux de la MA ont été développés afin de comprendre et de tester différents traitements dirigés contre cette pathologie. Cependant, aucun modèle de rongeur non transgénique, développant à la fois les plaques amyloïdes et la pathologie neurofibrillaire, n'est disponible à ce jour. L'objectif de cette étude est de développer le premier modèle non transgénique, développant les deux lésions histologiques caractéristiques de la MA chez le rat. Le principe consiste à réaliser une injection concomitante et intrahippocampale d'un AAV (virus associé aux adénovirus) recombinant contenant le gène humain de la protéine Tau présentant la mutation P301L, et du peptide Aβ1-42 qui est le principal composant des plaques amyloïdes. Après plusieurs expériences, nous avons obtenu un modèle animal représentatif des stades précoces de la MA, c'est-à-dire avec des lésions focalisées dans l'une des premières structures du cerveau affectée par la MA : l'hippocampe. La présence des deux lésions histopathologiques caractéristiques de la maladie, accompagnée d'une astrocytose, a été observée par immunohistofluorescence. Une détérioration de la mémoire concernant plus particulièrement la mémoire de travail, ainsi que des anormalités de l'activité électrique cérébrale et notamment durant les phases de sommeil paradoxal, enregistrées par électroencéphalographie, ont également été mises en évidence. / Alzheimer's disease (AD) is characterized by a progressive decline in cognitive function with a memory impairment, a brain atrophy, and two histological hallmarks observed from post-mortem examination: extracellular β-amyloid plaques and intracellular tangles of the Tau protein abnormally phosphorylated. Numerous animal models of AD have been developed to understand and to test drugs against this pathology. However, any non-transgenic model of rodent developing amyloid plaques and the neurofibrilary pathology is currently available. The aim of this study is to develop the first non-transgenic model producing the two histopathological features of AD in the rat. The principle is to perform a concomitant intrahippocampal injection of a recombinant AAV (Adeno-Associated Virus) containing the human transgene tau with the P301L mutation, and of Aβ1-42 peptide, the main component of the amyloid plaques. After several experiments, we have obtained an animal model representative of the early steps of AD, i.e. with lesions focalized in one of the first affected brain structures in the AD: the hippocampus. The presence of the two histopathological hallmarks has been observed by immunohistofluorescence and associated with an astrogliosis. A memory impairment concerning more particulary the working memory, and abnormalities of the electrical activity of the brain and of the rapid eye movement sleep recorded by electroencephalography, are also characterized.

The desire to enhance and make ourselves better is not a new one and it has continued to intrigue throughout the ages. Individuals have continued to seek ways to improve and enhance their well-being for example through nutrition, physical exercise, education and so on. Crucial to this improvement of their well-being is improving their ability to remember. Hence, people interested in improving their well-being, are often interested in memory as well. The rationale being that memory is crucial to our well-being. The desire to improve one’s memory then is almost certainly as old as the desire to improve one’s well-being. Traditionally, people have used different means in an attempt to enhance their memories: for example in learning through storytelling, studying, and apprenticeship. In remembering through practices like mnemonics, repetition, singing, and drumming. In retaining, storing and consolidating memories through nutrition and stimulants like coffee to help keep awake; and by external aids like notepads and computers. In forgetting through rituals and rites. Recent scientific advances in biotechnology, nanotechnology, molecular biology, neuroscience, and information technologies, present a wide variety of technologies to enhance many different aspects of human functioning. Thus, some commentators have identified human enhancement as central and one of the most fascinating subject in bioethics in the last two decades. Within, this period, most of the commentators have addressed the Ethical, Social, Legal and Policy (ESLP) issues in human enhancements as a whole as opposed to specific enhancements. However, this is problematic and recently various commentators have found this to be deficient and called for a contextualized case-by-case analysis to human enhancements for example genetic enhancement, moral enhancement, and in my case memory enhancement (ME). The rationale being that the reasons for accepting/rejecting a particular enhancement vary depending on the enhancement itself. Given this enormous variation, moral and legal generalizations about all enhancement processes and technologies are unwise and they should instead be evaluated individually. Taking this as a point of departure, this research will focus specifically on making a case for ME and in doing so assessing the ESLP implications arising from ME. My analysis will draw on the already existing literature for and against enhancement, especially in part two of this thesis; but it will be novel in providing a much more in-depth analysis of ME. From this perspective, I will contribute to the ME debate through two reviews that address the question how we enhance the memory, and through four original papers discussed in part three of this thesis, where I examine and evaluate critically specific ESLP issues that arise with the use of ME. In the conclusion, I will amalgamate all my contribution to the ME debate and suggest the future direction for the ME debate.