Pour rendre compte du traitement de l’information visuo-spatiale, l’hypothèse dominante est celle du calepin visuo-spatial (Baddeley, 1986). Cependant l’approche multi-systèmes est actuellement remise en question et les théories fonctionnelles défendent l’idée d’un système mnésique unique. C’est dans cette perspective que se situe notre recherche qui s’organise autour de trois questions. La première consiste à définir les traitements visuo-spatiaux mis en œuvre lors de la manipulation d’informations visuo-spatiales. La seconde tente d’établir des profils comportementaux des traitements visuo-spatiaux caractéristiques du vieillissement normal et pathologique (Alzheimer). La troisième porte sur l’expression de la flexibilité cognitive chez des sujets âgés lors de la résolution des blocs de Corsi.Deux expériences ont été réalisées dans lesquelles les participants (sujets Alzheimer et contrôles) devaient résoudre la tâche de Corsi, dans sa version ordre direct (expérience 1) et dans ces versions ordre direct et indirect (expérience 2). Les données ont été exploitées en recourant à une méthodologie d’analyse de protocoles individuels. Dans la première expérience, nous nous sommes intéressée aux erreurs rencontrées. Dans la seconde étude, nous avons étendu nos analyses aux traitements visuo-spatiaux inhérents à ces erreurs. Les résultats obtenus ont permis de définir cinq traitements visuo-spatiaux (vectoriel, vectoriel partiel, identité stricte, approximatif et mixte), de mettre en évidence des profils comportementaux concernant le traitement vectoriel partiel et identité stricte pour les sujets âgés sains lors de la condition indirecte et de montrer l’expression de flexibilité cognitive spontanée lors des traitements visuo-spatiaux séquentiels. Nos analyses ont ainsi permis de proposer une approche différente du traitement de l’information visuo-spatiale en substituant le concept de traitement visuo-spatial à celui de calepin visuo-spatial. / Currently, to account visuospatial information processing, the dominant hypothesis is that of the visuospatial sketchpad (Baddeley, 1896). However, such models postulating the existence of several independent modules are being questioned and recent functional theories defend a single memory system. Our research therefore is organized in this perspective around three questions.The first one aim to define the different visuospatial processing when visuospatial information is needed. The second one is to attempt to establish behavioral profiles of the visuospatial processing by normal ageing people and pathological one (Alzheimer). The third question is to express the cognitive flexibility of elderly patients when solving the Corsi block-tapping task.Two experiments were conducted where participants (seniors affected by Alzheimer’s disease ‘AD’ and a control group of elderly) had to solve the Corsi block-tapping task, in the direct condition (experiment 1) and in the direct and indirect conditions (experiment 2). The data were analyzed using the methodology of individual protocols analysis. In the first experiment, we examined different errors encountered during the resolution of the task. In the second research we extended our analysis to visuospatial processing associated with these errors.We identified five major visuospatial processing: “the vector processing”, “partially vectorial”, “strict identity”, “approximate identity” and “mixed”, to highlight behavioral profiles on the ‘partially vectorial’ processing and ‘strict identity’ to the healthy elderly subjects in the indirect condition and show the expression of spontaneous flexibility in AD patients and normal subjects. Our analysis allowed us to propose a different approach that improve knowledge about both normal and pathological (here Alzheimer’s disease) ageing. Analyzing the subjects in action, conducts to speak in terms of visuospatial processing rather than visuospatial sketchpad.

Résoudre aisément un problème, c’est-à-dire trouver une procédure rapide et efficace menant à la solution, nécessite de pouvoir considérer la situation selon plusieurs points de vue pour en choisir le plus pertinent, mais aussi de pouvoir en changer lorsque l’on se trouve face à une impasse, ce que l’on peut interpréter comme une expression de la flexibilité cognitive. Une adaptation des problèmes de jarres de Luchins a été présentée à 486 enfants scolarisés en CM1 et en CM2, afin d’observer leur capacité à faire preuve de flexibilité cognitive, puis, après tirage au sort, un certain nombre d’épreuves et d’échelles ont été proposés à 100 d’entre eux, lors de deux entretiens individuels. En effet, l’objet de cette étude est de montrer, auprès d’enfants se situant au niveau des opérations concrètes, que la flexibilité cognitive, qui leur permet d’élaborer des stratégies cognitives variées et de remettre en question leur point de vue initial, est liée, d’une part, à leur niveau de développement opératoire ainsi qu’à leur capacité à prendre en compte un point de vue différent du leur, et cela en lien avec leurs capacités de décentration et la présence d’une théorie de l’esprit. Mais il est, d’autre part, de montrer qu’au-delà de ces aspects développementaux, la flexibilité cognitive est également en lien avec la capacité de pouvoir confronter son point de vue à un autre, ce qui signifie qu’il ne s’agit pas seulement de prendre en compte un autre point de vue que le sien, mais aussi de pouvoir les prendre en compte en même temps, en concevant le fait que ces deux points de vue sur une même réalité sont susceptibles de coexister. Dès lors, faire preuve de flexibilité cognitive serait lié à la capacité de pouvoir confronter son propre point de vue à un autre, en se mettant à la place de l’autre tout en restant soi-même et en supportant la remise en cause que cela induit, donc aux capacités empathiques et à l’estime de soi. Cette recherche exploratoire a permis de valider partiellement nos hypothèses et a révélé, notamment à travers un essai de modélisation, certaines différences liées au genre. / Solving a problem easily, that is to say finding a fast and effective procedure leading to a solution, requires considering the situation from several points of view in order to choose the most appropriate one. However, this also requires being able to switch point of view when faced with a standstill ̶ which can be interpreted as an expression of cognitive flexibility. An adaptation of Luchins’ water jar experiment was presented to 486 school children from French CM1 and CM2 classes (England: Year 5 and Year 6), with the aim of observing their capacity to put cognitive flexibility into practice. Then, following a draw, several tests and levels were presented to 100 children from the group throughout two individual meetings. Indeed, the aim of this study is demonstrating that, for children who are at the stage of concrete operations, cognitive flexibility, which enables them to elaborate various cognitive strategies and question their initial point of view, is linked both to their operational development level and to their ability to take into account a point of view which differs from theirs, in association with their decentration abilities and the presence of a theory of mind. Furthermore, the goal of this study is also demonstrating that, beyond these developmental aspects, cognitive flexibility is also linked to the ability to confront one’s point of view with another one, which means not only taking into account someone else’s point of view but also having the ability to consider both perspectives simultaneously, appreciating that these two points of view on the same reality may co-exist. Consequently, displaying cognitive flexibility is supposedly linked to the capacity to confront one’s point of view with another one, by looking at things from the other’s perspective while also remaining ourselves and bearing the challenge that this implies ̶ and therefore linked to one’s self-esteem and empathetic capabilities. This exploratory research has enabled us to partially validate our hypotheses and has revealed, particularly through a modelling trial, some differences linked to gender.

A presente pesquisa centra-se no estudo das relações entre memória de curto prazo, memória de trabalho, velocidade de processamento, processamento visuoespacial, funções executivas, atenção seletiva e alternada e desempenho matemático, uma vez que essas relações podem esclarecer as diferenças entre os alunos na aprendizagem da matemática. O trabalho teve como objeto de observação crianças da 2ª série do ensino fundamental. Consiste em um estudo com base correlacional e comparativa. A amostra desta pesquisa é composta por 40 alunos, com idade entre 8 e 9 anos. A investigação envolvendo o funcionamento neuropsicológico e o desempenho cognitivo na aprendizagem matemática é relevante, pois para desenvolver habilidades de cálculo matemático é fundamental que o aluno tenha construído o conceito de número e esta construção está vinculada ao desenvolvimento das funções neuropsicológicas. O desempenho matemático é avaliado através da Prova de Aritmética de Capovilla, Montiel e Capovilla (2007) e as funções neuropsicológicas, através de quatro subtestes da Escala Wechsler WISCIII, que são: Memória de Curto Prazo – teste de Dígitos de Ordem Direta; Memória de Trabalho – Dígitos de Ordem Inversa; Velocidade de Processamento - Procurar Símbolos e Códigos; Percepção Visuoespacial – teste de Cubos. A Função Executiva é avaliada através do Teste das Trilhas de Montiel e Capovilla (2007) e a Atenção, através do Teste de Atenção por Cancelamento de Montiel e Capovilla (2007). Observa-se uma correlação significativa entre Desempenho Matemático e Memória de Curto Prazo, Velocidade de Processamento, Função Executiva e Atenção. Neste estudo, não se encontrou uma correlação estatisticamente significativa entre as funções Memória de Trabalho e Processamento Visuoespacial. / This paper approaches the relationship amongst neuropsychological functions –Short Term Memory (STM), Working Memory (WM), Speed Processing (SP), Visual Spatial Perception (VSP), Executive Functions (EF), Attention (A) and Math Performance (MP) in 2nd grade children at a public Elementary School from Porto Alegre. It is a comparative and correlation study. The sample of this research is composed for 40 pupils with are between 8 and 9 years. Research involving neuropsychological functioning and cognitive performance in mathematics is pertinent, for it is essential that the student build the notion of number in order to develop mathematical skills and such construction relies on the expansion of neuropsychological functions. The mathematical performance is measured by the Arthmetic Test of Capovilla, Montiel and Capovilla (2007) and the neuropsychological functions are verified by subtests Wechsler WIS CIII; Short Term Memory is assessed by the Digits in Direct Order, while the Working Memory is established by the Digits in Reverse Order. The speed processing is assessed through the use of Find Symbols and Codes activities, and spatial perception is confirmed by the utilization of cubes. The Executive Function is assessed by the Trail Making of Montiel and Capovilla (2007) and attention is assessed by the Attention Test for Cancellation of Montiel and Capovilla (2007). There is a momentous correlation amid math performance and Short-Term Memory, speed processing, executive function and attention. This study one did not mett, however, the establishment of a statistically significant correlation between the Working Memory functions and the Visual Spatial Processing.

No description available.

A presente pesquisa centra-se no estudo das relações entre memória de curto prazo, memória de trabalho, velocidade de processamento, processamento visuoespacial, funções executivas, atenção seletiva e alternada e desempenho matemático, uma vez que essas relações podem esclarecer as diferenças entre os alunos na aprendizagem da matemática. O trabalho teve como objeto de observação crianças da 2ª série do ensino fundamental. Consiste em um estudo com base correlacional e comparativa. A amostra desta pesquisa é composta por 40 alunos, com idade entre 8 e 9 anos. A investigação envolvendo o funcionamento neuropsicológico e o desempenho cognitivo na aprendizagem matemática é relevante, pois para desenvolver habilidades de cálculo matemático é fundamental que o aluno tenha construído o conceito de número e esta construção está vinculada ao desenvolvimento das funções neuropsicológicas. O desempenho matemático é avaliado através da Prova de Aritmética de Capovilla, Montiel e Capovilla (2007) e as funções neuropsicológicas, através de quatro subtestes da Escala Wechsler WISCIII, que são: Memória de Curto Prazo – teste de Dígitos de Ordem Direta; Memória de Trabalho – Dígitos de Ordem Inversa; Velocidade de Processamento - Procurar Símbolos e Códigos; Percepção Visuoespacial – teste de Cubos. A Função Executiva é avaliada através do Teste das Trilhas de Montiel e Capovilla (2007) e a Atenção, através do Teste de Atenção por Cancelamento de Montiel e Capovilla (2007). Observa-se uma correlação significativa entre Desempenho Matemático e Memória de Curto Prazo, Velocidade de Processamento, Função Executiva e Atenção. Neste estudo, não se encontrou uma correlação estatisticamente significativa entre as funções Memória de Trabalho e Processamento Visuoespacial. / This paper approaches the relationship amongst neuropsychological functions –Short Term Memory (STM), Working Memory (WM), Speed Processing (SP), Visual Spatial Perception (VSP), Executive Functions (EF), Attention (A) and Math Performance (MP) in 2nd grade children at a public Elementary School from Porto Alegre. It is a comparative and correlation study. The sample of this research is composed for 40 pupils with are between 8 and 9 years. Research involving neuropsychological functioning and cognitive performance in mathematics is pertinent, for it is essential that the student build the notion of number in order to develop mathematical skills and such construction relies on the expansion of neuropsychological functions. The mathematical performance is measured by the Arthmetic Test of Capovilla, Montiel and Capovilla (2007) and the neuropsychological functions are verified by subtests Wechsler WIS CIII; Short Term Memory is assessed by the Digits in Direct Order, while the Working Memory is established by the Digits in Reverse Order. The speed processing is assessed through the use of Find Symbols and Codes activities, and spatial perception is confirmed by the utilization of cubes. The Executive Function is assessed by the Trail Making of Montiel and Capovilla (2007) and attention is assessed by the Attention Test for Cancellation of Montiel and Capovilla (2007). There is a momentous correlation amid math performance and Short-Term Memory, speed processing, executive function and attention. This study one did not mett, however, the establishment of a statistically significant correlation between the Working Memory functions and the Visual Spatial Processing.

A presente pesquisa centra-se no estudo das relações entre memória de curto prazo, memória de trabalho, velocidade de processamento, processamento visuoespacial, funções executivas, atenção seletiva e alternada e desempenho matemático, uma vez que essas relações podem esclarecer as diferenças entre os alunos na aprendizagem da matemática. O trabalho teve como objeto de observação crianças da 2ª série do ensino fundamental. Consiste em um estudo com base correlacional e comparativa. A amostra desta pesquisa é composta por 40 alunos, com idade entre 8 e 9 anos. A investigação envolvendo o funcionamento neuropsicológico e o desempenho cognitivo na aprendizagem matemática é relevante, pois para desenvolver habilidades de cálculo matemático é fundamental que o aluno tenha construído o conceito de número e esta construção está vinculada ao desenvolvimento das funções neuropsicológicas. O desempenho matemático é avaliado através da Prova de Aritmética de Capovilla, Montiel e Capovilla (2007) e as funções neuropsicológicas, através de quatro subtestes da Escala Wechsler WISCIII, que são: Memória de Curto Prazo – teste de Dígitos de Ordem Direta; Memória de Trabalho – Dígitos de Ordem Inversa; Velocidade de Processamento - Procurar Símbolos e Códigos; Percepção Visuoespacial – teste de Cubos. A Função Executiva é avaliada através do Teste das Trilhas de Montiel e Capovilla (2007) e a Atenção, através do Teste de Atenção por Cancelamento de Montiel e Capovilla (2007). Observa-se uma correlação significativa entre Desempenho Matemático e Memória de Curto Prazo, Velocidade de Processamento, Função Executiva e Atenção. Neste estudo, não se encontrou uma correlação estatisticamente significativa entre as funções Memória de Trabalho e Processamento Visuoespacial. / This paper approaches the relationship amongst neuropsychological functions –Short Term Memory (STM), Working Memory (WM), Speed Processing (SP), Visual Spatial Perception (VSP), Executive Functions (EF), Attention (A) and Math Performance (MP) in 2nd grade children at a public Elementary School from Porto Alegre. It is a comparative and correlation study. The sample of this research is composed for 40 pupils with are between 8 and 9 years. Research involving neuropsychological functioning and cognitive performance in mathematics is pertinent, for it is essential that the student build the notion of number in order to develop mathematical skills and such construction relies on the expansion of neuropsychological functions. The mathematical performance is measured by the Arthmetic Test of Capovilla, Montiel and Capovilla (2007) and the neuropsychological functions are verified by subtests Wechsler WIS CIII; Short Term Memory is assessed by the Digits in Direct Order, while the Working Memory is established by the Digits in Reverse Order. The speed processing is assessed through the use of Find Symbols and Codes activities, and spatial perception is confirmed by the utilization of cubes. The Executive Function is assessed by the Trail Making of Montiel and Capovilla (2007) and attention is assessed by the Attention Test for Cancellation of Montiel and Capovilla (2007). There is a momentous correlation amid math performance and Short-Term Memory, speed processing, executive function and attention. This study one did not mett, however, the establishment of a statistically significant correlation between the Working Memory functions and the Visual Spatial Processing.

We investigated the hypermediatic integration of free information and communication technology in study activities, mediated by Free Virtual Teaching and Learning Environment, more specifically Moodle, in a course at the Federal University of Santa Maria. Our goal was to identify the advances and challenges of this integration in teaching and learning mediated by Moodle, in order to bring contributions to the educational process. Thus, we use the concept of educational action research, which involved a retrospective movement (questioning and reflective understanding of practice) and prospective (planning of new actions guided by the results already shown). In this work, we have also taken the methodological guidance of three matrices: Problem-Dialog Matrix (PDM), Thematic-Organizing Matrix (TOM) and Thematic-Analytical Matrix (TAM), which were organized respectively in three stages of spiral-cycles: thematic concern, organization and analysis. Study activities, dialog applied to problem-searching, educational hypermedia and cognitive flexibility were concepts that guided the development of hypermediatic study activities. Then, we conclude that the study activities organized in hypermediatic mode, mediated by Moodle, from a socio-constructivist, problem-dialog and Cognitive Flexibility Theory perspective, present a great scholar potential for the critical appropriation of scientific knowledge in relation to different contexts of reality. / Investigamos a integração hipermidiática das Tecnologias da Informação e da Comunicação livres nas atividades de estudo, mediadas por Ambiente Virtual de Ensino-Aprendizagem Livre, mais especificamente pelo Moodle, em um curso presencial da Universidade Federal de Santa Maria. Nosso objetivo foi detectar quais avanços e desafios dessa integração no ensino-aprendizagem mediado pelo Moodle, a fim de trazer contribuições para o processo educacional. Para isso, empregamos a concepção de trabalho de pesquisa denominada investigação-ação educacional, o que envolveu um movimento retrospectivo (problematização e compreensão reflexiva da prática) e prospectivo (planejamento de novas ações orientado pelos resultados já evidenciados). Nesse trabalho, também adotamos a orientação metodológica de três matrizes: Matriz Dialógico-Problematizadora (MDP), Matriz Temático-Organizadora (MTO), e Matriz Temático-Analítica (MTA), que foram organizadas respectivamente em três etapas dos ciclos-espiralados: preocupação temática, organização e análise. Os conceitos atividades de estudo, diálogoproblematizador, hipermídia educacional e flexibilidade cognitiva guiaram o desenvolvimento das atividades de estudo hipermidiática. Ao final desse percurso investigativo, concluímos que as atividades de estudo organizadas de modo hipermidiático e dialógico-problematizador, mediadas pelo Moodle, na perspectiva sócio-construtivista e da Teoria da Flexibilidade Cognitiva, apresentam grande potencial escolar para a apropriação crítica do conhecimento científico face aos diversos contextos da realidade.

Cognitive flexibility can be described as adaptive ability to change one's behavior in response to the environment. Psychological tests measure cognitive flexibility mainly as an ability to switch between different cues, tasks or objects. This thesis is focused on cognitive flexibility in patients with obsessive compulsive disorder (OCD). To assess it, participants were tested in two different virtual tests of cognitive flexibility in spatial navigation task: Active allothetic place preference and Active allothetic place avoidance. In one of the tests participants have to navigate in rotating arena towads invisble goal (AAPP). In the other one they have to avoid invisible sector where time is counted upon entering (AAPA). As the sector and goal are visually imperceptible, participants have to use only cues inside and outside the arena and are also informed about entering the sector by sound signal. The sector changes its position from stable position in room frame to stable position in arena frame between conditions. Therefore, participants have to learn to switch between room and arena frame to sucessfully solve the task. Results of this study suggest that OCD patients are significantly worse in estimating position of the goal in AAPP, especially after change of condition. Further comparsion of...

Les enfants qui ont subi une asphyxie périnatale modérée (MPA) risquent de développer des déficits cognitifs et comportementaux subtils et durables, notamment des troubles d'apprentissage et des problèmes émotionnels. Comprendre les mécanismes sous-jacents est une étape essentielle pour concevoir une thérapie ciblée. Déterminer comment le développement du cerveau est corrélé entre les humains et les rongeurs n'est pas simple, mais il existe également un alignement inter-espèces considérable en termes d'étapes clés du développement. Sur la base des changements biochimiques et neuroanatomiques au cours du développement précoce, le consensus général est qu'un cerveau de rongeur P8-10 correspond à peu près au cerveau d'un enfant à terme ; par conséquent, nous avons utilisé cette fenêtre temporelle comme référence pour développer un modèle préclinique de MPA chez la souris. Nous avons d'abord établi un protocole qui nous permet d'observer de manière fiable les crises induites par l'hypoxie chez les souris postnatales. Nous avons constaté que l'exposition de chiots P8-9 directement à 4 % d'O2 pendant 8 minutes induit de manière fiable des crises avec une latence d'environ 5 minutes chez 3 souches de souris (FVB, C57Bl/6, 129S6). Cet aspect est cliniquement pertinent car les convulsions sont la caractéristique néonatale la plus importante de l'encéphalopathie de stade 2 (modérée) telle que définie par l'échelle de Sarnat. Les souris MPA adultes présentent des séquelles à long terme sur des performances cognitives spécifiques, notamment des déficits de la mémoire de reconnaissance et de la flexibilité cognitive, mais aucune altération du comportement moteur et émotionnel. Le cortex préfrontal (PFC) régule la flexibilité cognitive et le comportement émotionnel. Les neurones qui libèrent la sérotonine (5-HT) projettent vers le PFC, et les composés modulant l'activité 5-HT influencent l'émotion et la cognition. On ne sait pas si les dérégulations de la 5-HT contribuent aux problèmes cognitifs induits par le MPA. Dans une première étude, nous avons trouvé que les niveaux d'expression de 5-HT, quantifiés par immunohistochimie, et de libération de 5-HT, quantifiés par microdialyse in vivo chez des souris éveillées, sont réduits dans le PFC de souris MPA adultes. Les souris MPA présentent également une régulation de la température corporelle altérée après l'injection de l'agoniste des récepteurs 5-HT1A, 8-OH-DPAT, suggérant la présence de déficits dans la fonction des auto-récepteurs 5-HT sur les neurones du raphé. Enfin, le traitement chronique de souris MPA adultes avec de la fluoxétine, un inhibiteur du transporteur de recapture de la 5-HT, ou l'agoniste des récepteurs 5-HT1A, la tandospirone, sauve la flexibilité cognitive et les troubles de la mémoire. Ensemble, ces données démontrent que le développement de la fonction du système 5-HT est vulnérable à une asphyxie périnatale modérée. L'hypofonctionnement de la 5-HT pourrait à son tour contribuer à une déficience cognitive à long terme à l'âge adulte, indiquant une cible potentielle pour les thérapies pharmacologiques. Les circuits GABAergiques comprennent une variété étonnante de différents types de cellules, qui sont probablement recrutées par différents événements comportementaux. Un sous-type important de cellules GABAergiques, les cellules positives à la parvalbumine (PV), génèrent des potentiels d'action à haute fréquence et synchronisent l'activité des neurones pyramidaux excitateurs. Les cellules PV sont particulièrement importantes pour la génération d'oscillations gamma, qui à leur tour régulent de nombreuses fonctions cognitives, notamment le traitement attentionnel axé sur les objectifs et la mémoire de travail. Des découvertes récentes indiquent que les cellules PV utilisent beaucoup plus d'énergie que les autres neurones corticaux, ce qui peut les rendre très vulnérables aux conditions de stress métabolique et oxydatif causées par le MPA. Nos données ont montré que l'expression de PV est altérée chez les souris MPA adultes. Nous avons en outre constaté que le niveau d'expression du récepteur de la neurotrophine p75NTR, qui limite la maturation des cellules PV au cours de la première semaine postnatale, est augmenté chez les souris MPA. La suppression génétique de p75NTR dans les neurones GABAergiques exprimant le facteur de transcription Nkx2.1, qui comprend les cellules PV, protège les souris de la perte de niveaux de PV et des effets cognitifs à long terme du MPA. Enfin, un traitement d'une semaine avec un inhibiteur de p75NTR commençant après le MPA sauve complètement les déficits d'activité cognitive et corticale chez les souris adultes. L'ensemble de ces données révèle une cible moléculaire potentielle pour le traitement des altérations cognitives causées par le MPA. / Children who experienced moderate perinatal asphyxia (MPA) are at risk of developing long lasting subtle cognitive and behavioral deficits, including learning disabilities and emotional problems. Understanding the underlying mechanisms is an essential step for designing targeted therapy. Determining how brain development correlates between humans and rodents is not straightforward, however there is also considerable cross-species alignment in terms of key developmental milestones. Based on biochemical and neuroanatomical changes during early development, the general consensus is that a P8-10 rodent brain corresponds roughly to the brain of a term infant; therefore, we used this time window as reference to develop a preclinical model of MPA in mouse. We first established a protocol that allows us to reliably observe hypoxia-induced seizures in postnatal mice. We found that exposing P8-9 pups directly to 4% O2 for 8 minutes reliably induces seizures with a latency of about 5’ in 3 mouse strains (FVB, C57Bl/6, 129S6). This aspect is clinically relevant as seizures are the most prominent neonatal hallmark of Stage 2 (Moderate) encephalopathy as defined by the Sarnat Scale. Adult MPA mice show long-term sequelae on specific cognitive performance, including deficits in recognition memory and cognitive flexibility, but no impairment in motor and emotional behavior. The prefrontal cortex (PFC) regulates cognitive flexibility and emotional behavior. Neurons that release serotonin (5-HT) project to the PFC, and compounds modulating 5-HT activity influence emotion and cognition. Whether 5-HT dysregulations contribute to MPA-induced cognitive problems is unknown. In a first study, we found that 5-HT expression levels, quantified by immunohistochemistry, and 5-HT release, quantified by in vivo microdialysis in awake mice, are reduced in PFC of adult MPA mice. MPA mice also show impaired body temperature regulation following injection of the 5-HT1A receptor agonist 8-OH-DPAT, suggesting the presence of deficits in 5-HT auto-receptor function on raphe neurons. Finally, chronic treatment of adult MPA mice with fluoxetine, an inhibitor of 5-HT reuptake transporter, or the 5-HT1A receptor agonist tandospirone rescues cognitive flexibility and memory impairments. All together, these data demonstrate that the development of 5-HT system function is vulnerable to moderate perinatal asphyxia. 5-HT hypofunction might in turn contribute to long-term cognitive impairment in adulthood, indicating a potential target for pharmacological therapies. GABAergic circuits comprise an astonishing variety of different cell types, which are likely recruited by different behavioral events. An important subtype of GABAergic cells, the fast-spiking, parvalbumin-positive (PV) cells, generate action potentials at high frequency and synchronize the activity of excitatory pyramidal neurons. PV cells are particularly important for the generation of gamma oscillations, which in turn regulate many cognitive functions including goal-directed attentional processing and working memory. Recent findings indicate that PV cells utilize much more energy than other cortical neurons, which may render them highly vulnerable to conditions of metabolic and oxidative stress caused by MPA. Our data showed that PV expression is impaired in adult MPA mice. We further found that the expression level of the neurotrophin receptor p75NTR, which limits PV cell maturation during the first postnatal week, is increased in MPA mice. Genetic deletion of p75NTR in GABAergic neurons expressing the transcription factor Nkx2.1, which include PV cells, protects mice from PV levels loss and the long-term cognitive effects of MPA. Finally, one week treatment with a p75NTR inhibitor starting after MPA completely rescues the cognitive and cortical activity deficits in adult mice. All together this data reveals a potential molecular target for the treatment of the cognitive alterations caused by MPA.

No description available.