Les fonctions exécutives (FE), et en particulier le Contrôle Inhibiteur (CI), jouent un rôle très important dans la réussite académique et professionnelle ainsi que dans la physiopathologie de nombreux troubles psychiatriques. L'adolescence est une période critique du développement du CI, ce dernier étant sous-tendu en particulier par la maturation tardive du cortex préfrontal jusqu’au début de l'âge adulte. Le premier objectif de cette thèse a été de cartographier les bases neurales du CI durant le développement et d'en évaluer leurs spécificités en les comparant avec celles de la mémoire de travail (MdT), une autre composante clef des FE. À partir d'une méta-analyse des études en IRMf du CI et de la MdT incluant 845 enfants, 1377 adolescents et 10235 adultes, nous avons identifié des modifications de l'activité fonctionnelle, à savoir le passage d'un réseau diffus à un réseau focal plus spécialisé avec l'âge, en accord avec un modèle dynamique du développement cérébral. Un large recouvrement de régions fronto-pariétales pour le CI et la MdT a également été détecté, ce qui soulève la question de la spécificité des processus et des tâches de ces deux FE. Par la suite, nous avons analysé l'effet à long terme du neuro-développement précoce sur le CI à partir de l'étude de la morphologie sulcale, un paramètre anatomique du cerveau déterminé lors de la vie fœtale. Dans un premier temps, nous avons montré, d'après une analyse longitudinale de 243 IRM, la stabilité du motif des sillons durant le développement. Nous avons par la suite établi que les polymorphismes sulcaux du cortex cingulaire antérieur et du sillon frontal inférieur contribuaient, de manière complémentaire, à l'efficience du CI chez l'enfant et également chez l'adulte. Enfin, nous nous sommes intéressés à l’entraînement cognitif au CI à l'adolescence, une période de très grande plasticité cérébrale et de sensibilité à l'environnement. Nous avons étudié chez 49 adolescents de 16-17 ans l'effet d'un entraînement intensif sur tablette tactile (25 sessions de 15 minutes par jour) au CI versus Contrôle Actif aux niveaux cognitif et cérébral (IRMf : tâches de stop-signal, de matrice de points, du réseau attentionnel et de gratification retardée). Nous avons en particulier évalué l'effet des facteurs neurodéveloppementaux précoces sur la réceptivité à l’entraînement au CI. Ces travaux s'inscrivent dans un nouveau champ de recherche interdisciplinaire à l'interface entre les neurosciences et la psychologie. Dans une perspective translationnelle éducative et thérapeutique, il vise à évaluer le plus finement possible, grâce à l'imagerie cérébrale anatomique et fonctionnelle, quelles interventions pédagogiques et thérapeutiques sont susceptibles d'aider au mieux le cerveau à surmonter des difficultés d'ordre cognitif. / Executive functions (EF), including Inhibitory Control (IC), play a major role in academic and professional achievement, as well as in the pathophysiology of many psychiatric disorders. Adolescence is a critical period in IC development as it is underlain by the protracted maturation of prefrontal cortex until early adulthood. The first objective of this thesis was to examine the neural bases of IC during development and to evaluate their specificities by comparing them with the working memory (WM), another key component of EF. Based on a meta-analysis of IC and WM fMRI studies including 845 children, 1377 adolescents and 10235 adults, we identified changes in functional activity with a shift from a diffuse to a more focal and specialized network with age. These results support the model of dynamic neurofunctional development. Moreover, a large overlap of fronto-parietal regions was found for IC and WM, which raises issues regarding the specificities of IC and WM processes and tasks. Second, we analyzed the long-term effect of early neurodevelopment on IC based on the sulcus morphology, an anatomical brain feature determined during fetal life. We showed, using a longitudinal analysis of 243 MRIs, that folding patterns are fixed from childhood to adulthood. Subsequently, we established that the sulcal polymorphisms of the anterior cingulate cortex and the inferior frontal sulcus complementary contributed to IC efficiency in both children and adults. Finally, we studied IC training in adolescence, a period of high brain plasticity and environmental sensitivity. We examined the effects of an intensive IC training (25 sessions of 15 minutes per day) versus active control training group on touchscreens in 49 adolescents (16-17 years-old) on cognitive and brain levels (fMRI: stop-signal, dot matrix, attentional network and delayed gratification tasks). We also assessed the effect of early neurodevelopmental factors on IC training receptivity. This thesis is part of a new field of interdisciplinary research, at the interface between neurosciences and psychology. It includes translational educational and therapeutic perspectives, with aims at evaluating as finely as possible, using anatomical and functional brain imaging, what pedagogical and therapeutic interventions are likely to help the brain to overcome cognitive difficulties.

Collision avoidance systems have become an integrated part of modern vehicles and aim to avoid accidents or mitigate the crash severity for the occupant. For example, the autonomous emergency braking system influences the pre-crash state of the occupant in sitting posture, stress state, or velocity. The occupant might try to retain its posture by activating muscles, which induce muscle bracing and could counteract the movement of the occupant in the pre-crash phase.  Therefore, it is essential to study the influence of active musculature on occupant response in pre-crash and crash events. A finite element human body model (HBM) with and without closed-loop muscle activation control was used to simulate the occupant response during those events. Comparing the HBM responses & head kinematics reveal an influence of muscle bracing in the evasive braking manoeuvre. Simulating the pre-crash and in-crash phase in two stages can provide multiple benefits. However, the correlation between a single-stage simulation (baseline) and a two-stage simulation needs to be investigated. The baseline simulation uses an active HBM to model an occupant during an evasive braking manoeuvre and the muscles are deactivated when entering the frontal impact phase. The parameters of the final pre-crash state, which are needed to mimic the baseline’s response when transitioning from the pre-crash to the in-crash event are investigated in this study. For that reason, sitting position, stress state and velocity are transferred respectively to the initial passive in-crash HBM state. The simulations enabled the comparison of occupant response and calculation of cross-correlation. Each retainment strategy gave a good cross-correlation with the baseline simulation. / Kollisionsundvikande system har blivit en viktig del i moderna fordon där syftet är att undvika olyckor samt att minska allvarhetsgraden av olyckor för de åkande. Ett exempel är nödbromssystem som kan påverka den åkandes initiala tillstånd direkt före en krock som, till exempel, sittposition, spänningstillstånd, eller initial hastighet inför krock. Den åkande kan försöka att bibehålla sin hållning genom att aktivera sina muskler vilket påverkar rörelsen av dess kropp under för-krocks fasen. Det är därför viktigt att studera hur aktiva muskler påverkar rörelsen av kroppen hos den åkande under både före krocksfasen och själva krockfasen. En finit element humanmodell (HBM) med och utan reglerad muskelaktivitet används för att prediktera responsen hos den åkande i båda faserna. En jämförelse mellan simuleringarna visar att aktiva muskler kan påverka åkandekinematiken under bromsningsförloppet. Att simulera fasen före krock och fasen under krock i två steg kan medföra flera fördelar. Korrelationen mellan en enkelstegssimulering (originalsimulering) och en tvåstegssimulering måste dock studeras. Som originalsimulering används en aktiv HBM för att modellera den åkande under för-krocksfasen där den reglerade muskelaktiviteten inaktiveras under krockfasen. I denna studie undersöks den åkandes initiala tillstånd före krocken som behövs för att efterlikna originalsimulerings respons vid övergången från för-krocksfasen till krockfasen. Av den anledningen mappas det passiva HBM-tillståndet till det slutliga tillståndet av före krocksfasen för sittposition, spänningstillstånd respektive hastighet. Simuleringarna möjliggjorde en jämförelse av åkande respons och beräkning av korskorrelation. Varje mappningsstrategi gav en bra korskorrelation med originalsimuleringen.

In this thesis we examine the question whether it is possible to model approach and avoidance behaviour with probabilistic machine learning. The results from this project will primarily aid in our collective understanding of human existence. Secondly, it will extend the knowledge with regards to probabilistic machine learning in the Neuroscience domain. We aid this through building a Variational Recurrent Neural Network (VRNN) that is trained on Electroencephalography (EEG)-data from participants that is subjected to odours with varying pleasantness. The pleasantness of the odours is used to divide the participants into two classes based on their self reported experience. This data is used to train the VRNN. The performance of the VRNN is evaluated by how well we are able to reconstruct the original data from a low dimensional latent representation. In this task the model performs on a similar level as related works. We further investigate how changes in the latent space effects reconstructed data. Despite being disentangled, the latent variables are hard to interpret. Furthermore we try to classify and cluster the latent space as either approach or avoidance behaviour with a Support Vector Machine and Uniform Manifold Approximation. The classification results are only slightly better than random, indicating that the learned latent space is not suitable for the task This is most likely due to the patterns that make up approach and avoidance behaviour is seen as noise by the VRNN. This leads to the patterns not being accurately modelled. This is shown by the evidence that frontal α -asymmetry that exists in the data is not reconstructed by the model. The conclusion is therefore that a VRNN is less suitable for modelling underlying behaviour from raw EEG data due to the low signal to noise ratio. We instead suggests to focus on specific frequency ranges in specific regions when applying machine learning in this domain. / Den här uppsatsen behandlar frågan huruvida det är möjligt att modellera närmande och frånstötande beteendemönster med hjälp av maskininlärning. Resultaten från detta projekt ämnar huvudsakligen att främja vidare förståelse av den mänskliga existensen. Vidare ämnar den även att utvidga förståelsen av hur probabilistisk maskininlärning kan användas för att utforska dylika hänseenden. Vi genomför detta genom att bygga en Variational Recurrent Neural Network-modell (VRNN) som tränas på data från experiment där personer utsätts för olika lukter samtidigt som deras Elektroencefalografi (EEG) spelas in. Deltagarna delas in i två klasser beroende på deras självrapporterade upplevelse av luktens njutbarhet. Maskininlärningsmodellen utvärderas genom att vi analyserar hur väl den lyckas rekonstruera datan. Detta lyckas den väl med. Vidare så undersöker vi hur förändringar i modellens latenta rum påverkar rekonstrueringen av datan. Resultaten från det experimentet är ej tydliga. Vidare så försöker vi klassificera och klustra det latenta rummet med avseende på närmande och frånstötande beteende med hjälp av en Support Vector Machine och Uniform Manifold Approximation. Resultaten från dessa experiment är att vi inte lyckas klassificera eller klustra det latenta rummet med avseende på närmande och frånstötande beteende bättre än slumpen. Vi argumenterar för att detta beror på att de underliggande mönster som skapar dessa beteenden ses som brus av VRNN-modellen och därmed inte modelleras. Detta visas genom att frontal α-asymmetri som existerar i datan ej rekonstrueras av modellen. Slutsaten blir därmed att en VRNN är mindre passande att använda vid modellering av underliggande beteenden av obehandlad EEG data. Detta på grund av det låga signal till brus-förhållandet i EEG-datan. Vi föreslår att istället fokusera på specifika frekvensområden i specifika hjärnregioner när maskininlärning appliceras på EEG.

The investigation of the atmospheric fate and transport of semi-volatile organic compounds (SOCs) often requires the sampling of large volumes of air (>100 m3) in a relatively short period of time. Conventionally high-volume pumps are not suitable for remote areas without access to reliable network power. We have developed a flow through sampler for such situations. It consists of a horizontally-oriented flow-tube, that can collect gaseous and particle-bound SOCs from large volumes of air by turning into the wind and having the wind blow through a porous sampling medium such as polyurethane foam. Through both indoor and outdoor experiments, we quantified its air sampling rate (through battery operated anemometers inside and outside of the flow tube), its sampling efficiency (by theoretical plate number analysis of the break-though curves for PCBs, PAHs, OCPs and PBDEs), and its accuracy (by comparison of concentrations, time trends, temperature dependences and isomer ratios with those obtained by conventional high-volume sampling) under conditions of constant and variable meteorological conditions (wind speed, temperature). The flow-through sampler was deployed to monitor SOC concentrations at a remote Chinese research station located close to Nam Co Lake, Tibet. During the campaign, fifteen 1 month-long samples were taken, corresponding to sample volumes between 5,000 and 20,000 m3. Despite those large sample volumes, only HCB and HCHs experienced break-through, but application of frontal chromatograph theory allows the estimation of breakthrough-corrected air concentrations even for those relatively volatile SOCs. The pesticide levels at Nam Co are generally very low. Most pesticides had higher levels during summer, resulting in a strong temperature dependence. This is correlated with air mass origin across the Himalayas in the Gangetic plains of India and Bangladesh. The flow through sampler constitutes a feasible method for reliably and quantitatively collecting SOCs from large air volumes.

Geólogo / En los Andes Centrales las estructuras compresivas presentan variaciones a lo largo del rumbo en su geometría y cinemática. Ejemplo de ello son las estructuras de orientación NNE SSW que involucran al basamento paleozoico de las cuencas de Lautaro y Lagunillas en la Cordillera Frontal de la tercera región; consistiendo principalmente en fallas invertidas positivamente y fallas inversas. A pesar de existir mapeo geológico (1:100.000) y secciones balanceadas para la zona, aún existen interrogantes como la cinemática y proyección en profundidad de las estructuras, y su relación con estructuras heredadas de eventos tectónicos previos. Este trabajo busca resolver estas interrogantes al evaluar si el acortamiento de discontinuidades angulares en el basamento, relacionadas con procesos tectónicos extensionales, es un parámetro influyente en el desarrollo de dominios estructurales oblicuos. Mediante la integración de datos de superficie y modelos análogos. Se utilizaron 3 conjugaciones diferentes de una orientación N20E como discontinuidad de velocidad. Llevándose a cabo 3 series de modelos, tanto extensivos, como extensivos sometidos a compresión; utilizando arena como principal material de modelación. Los resultados muestran que durante la compresión de un sistema extensional pre-existente (hemi-grabenes): (a) las estructuras extensionales previas no necesariamente conservan su orientación, pudiendo rotar; (b) la orientación del sistema pre-existente, puede influenciar la orientación de las nuevas estructuras inversas, adoptando estas últimas un lineamiento paralelo al pre-existente; (c) pudiendo además estas nuevas estructuras enmascarar la configuración estructural del sistema pre existente, tanto en superficie como en profundidad; o (d) la reactivación del borde de cuenca propagarse como short-cuts en el basamento. Al contrastar los modelos con el prototipo natural, destaca: (a) el límite occidental de la Cuenca de Lagunillas se puede aproximar como una falla normal de borde de cuenca decapitado; (b) el lineamiento actual de la Cuenca Lautaro puede asociarse a una discontinuidad en la corteza de orientación N20ºE durante la extensión, pudiendo esta herencia influenciar la orientación de las estructuras inversas de lineamiento similar desarrolladas durante el periodo compresivo; (c) los resultados son aplicables a otras latitudes de la Cordillera Frontal, reproduciendo geometrías presentes en el Valle del Tránsito.

A ketamina, antagonista não competitivo de receptores NMDA, apresenta potentes efeitos psicomiméticos, sendo capaz de acentuar o estado psicótico de pacientes esquizofrênicos. Uma das áreas cerebrais afetadas por seu uso é o córtex pré-frontal, já que o desempenho em tarefas que dependem de sua atividade é profundamente alterado pela administração aguda de ketamina. Assim como na esquizofrenia, estas alterações podem sofrer influência de fatores hormonais, alterações estas que podem ser explicadas pelos efeitos dos hormônios sexuais femininos, como o estrogênio, os quais apresentam um papel regulador sobre os sistemas dopaminérgicos, serotonérgicos, glutamatérgicos e GABAérgicos, todos afetados pelos efeitos agudos e crônicos do uso de ketamina. Este projeto, portanto, teve como meta avaliar os possíveis efeitos da administração crônica e retirada de ketamina sobre a expressão de comportamentos relacionados à ansiedade humana em ratas da linhagem Wistar, assim como a influência dos hormônios estradiol e a progesterona sobre esta variável. As possíveis alterações farmacológicas induzidas pela administração crônica de ketamina sobre os sistemas dopaminérgicos e serotoninérgicos da divisão pré-límbica (PrL) do córtex pré-frontal medial serão avaliadas através da injeção local de antagonista/agonista específicos. Nossos dados reforçam a ideia de que a ketamina demonstra de forma significativa a expressão da resposta aprendida de medo. E também, os dados mostram que a abstinência da droga altera este comportamento, particularmente a capacidade cognitiva relacionada ao encadeamento de estímulos. Da mesma forma que outras drogas de abuso, estas alterações parecem envolver tanto o sistema dopaminérgico quanto serotoninérgico do CPFm. / Ketamine, a non-competitive antagonist of NMDA receptors, has potent psychomimetic effects, being able to accentuate the psychotic state of schizophrenic patients. One of the brain areas affected by its use is the prefrontal cortex, since performance in tasks that depend on its activity is profoundly altered by the acute administration of ketamine. As in schizophrenia, these changes may be influenced by hormonal factors, which can be explained by the effects of female sex hormones, such as estrogen, which play a role in the dopaminergic, serotonergic, glutamatergic and GABAergic systems, all affected acute and chronic effects of ketamine use. This project therefore aimed to evaluate the possible effects of chronic administration and withdrawal of ketamine on the expression of behaviors related to human anxiety in Wistar rats, as well as the influence of the hormones estradiol and progesterone on this variable. The possible pharmacological changes induced by chronic ketamine administration on the dopaminergic and serotonergic systems of the prelambial (PrL) division of the medial prefrontal cortex will be assessed by specific local antagonist / agonist injection. Our data reinforce the idea that ketamine demonstrates significantly the expression of the learned response of fear. Also, the data show that drug abstinence alters this behavior, particularly the cognitive capacity related to the chaining of stimuli. Like other drugs of abuse, these changes appear to involve both the dopaminergic and serotonergic system of CPFm.

Estudos apontam a substância cinzenta periaquedutal (PAG) como um sítio crítico para a expressão de vários comportamentos motivados. A porção rostrolateral da PAG (PAGrl), tem um papel chave na regulação da motivação na caça predatória, e modularia mecanismos de recompensa associados ao comportamento alimentar e busca por droga, a partir de projeções para área tegmental ventral e núcleo acumbens; o que dependeria da ligação com neurônios orexinérgicos da área hipotalâmica lateral (LHA). A PAGrl, está mobilizada nos comportamentos de busca por droga assim como na caça predatória. As principais regiões que aferentam a PAGrl são áreas do córtex pré-frontal medial (mPFC) onde a PAGrl integraria tais aferencias e modularia a LHA. Os resultados corroboram com a hipótese, pois lesões no mPFC diminuíram a busca por droga e vimos que neurônios da PAGrl mobilizados no comportamento, que recebem aferências do mPFC, seriam os mesmos que se projetam para LHA e que a PAGrl teria papel crítico na promoção do comportamento de busca por droga no CPP para sulfato de morfina. / Studies show a periaqueductal gray (PAG) as a critical place for an expression of motivated behaviors. The rostrolateral portion of PAG (PAGrl), is a key role in the regulation of motivation in predatory hunting, and modulates, reward mechanisms associated with drug and food seeking, through projections to ventral tegmental area and the nucleus accumbens; what would depend on the connection with orexin neurons of the lateral hypothalamic area (LHA). The PAGrl, is mobilized in predatory hunting as drug seeking. The main region that sends projections to PAGrl is the medial prefrontal cortex (mPFC), where PAGrl integrate such afferent and modulates the LHA. Our results corroborate the hypothesis, because mPFC injuries, decreased drug seeking and we observed that PAGrl neurons mobilized in behavior, and also receive afferents from mPFC, would be the same as projecting to LHA, thus PAGrl had critical role in promotion of drug seeking behavior during the CPP for morphine sulfate.

O córtex pré-frontal (PFC) participa do controle do comportamento de busca por droga e se projeta para a coluna rostrolateral da substância cinzenta periaquedutal (PAGrl) que por sua vez se projeta para o sistema orexinérgico da área hipotalâmica lateral (LHA) que controla comportamentos que oferecem recompensa através de projeções para o sistema dopaminérgico mesolímbico. O objetivo do trabalho é investigar a participação da PAGrl e a sua relação com o PFC e com o sistema orexinérgico da LHA na expressão do comportamento de busca por droga. Submetemos ratos Wistar ao condicionamento de preferência por lugar para sulfato de morfina e notamos que o PFC, a PAGrl e a LHA estão ativados em animais que expressaram tal comportamento. Após, realizamos lesões neuroquímicas bilaterais no PFC e notamos a ausência da busca pela droga nestes animais e da diminuição da ativação da PAGrl e do sistema orexinérgico da LHA. Posteriormente realizarmos lesões neuroquímicas por NMDA na PAGrl e notamos a ausência do comportamento e diminuição de duplas marcações para Fos e orexina na LHA. Os resultados indicam que a PAGrl exerceria um papel crítico para o comportamento de busca por droga, integrando aferências provenientes do PFC para modular os neurônios orexinérgicos da LHA. / The prefrontal cortex (PFC) is involved with planning of the drug seeking behavior and projects itself to the rostrolateral periaqueductal gray (PAGrl) that through projections for the orexin neurons in the lateral hypothalamic area (LHA), participates in the control of behavior that offer rewards. The LHA controls drug reward through projections for the mesolimbic dopaminergic system. This study aims to investigate the relationship between the PFC, PAGrl and orexin neurons in the LHA in drug seeking behavior. We did a morphine conditioned place preference (CPP) procedure in intact, bilateral PAGrl-lesioned and bilateral PFC-lesioned Wistar rats and investigated the pattern of Fos expression. The intact animals displayed such behavior and presented an increase in Fos activation in the PFC, rlPAG and LHA orexinergic neurons. Conversely, PAGrl-lesioned and PFC-lesioned animals did not display this behavior and reduced the activation of orexin neurons in the LHA. PFC-lesioned animals presented a reduction of the Fos activation in the rlPAG. The results suggest a pathway involving the PFC, PAGrl and LHA orexinergic cell group underlying the CCP, where the rlPAG would integrate inputs from the PFC to control the LHA orexinergic cell group.

Acredita-se que quantidades elevadas de glutamato estejam relacionadas à neurobiologia da depressão e trabalhos recentes indicam que a quantidade de glutamato cortical está aumentada em pacientes depressivos quando comparada a indivíduos sadios. Dentre as estruturas corticais, o córtex pré-frontal medial ventral (CPFMv), dividido em infralímbico (IL) e pré-límbico (PL), tem sido mais frequentemente implicado no desenvolvimento de transtornos mentais, como a depressão. Considerando evidências de que o IL e o PL podem agir de forma diferente quanto ao controle emocional em resposta ao estresse, o presente trabalho visou avaliar a hipótese de participação da neurotransmissão glutamatérgica do CPFMv, IL e PL, no desenvolvimento das respostas comportamentais ao estresse de nado forçado, um modelo preditivo de efeitos antidepressivos. Para tal, investigamos os efeitos induzidos pela administração no IL ou no PL, de LY 235959, um antagonista dos receptores glutamatérgicos do tipo NMDA, em três momentos diferentes, em animais submetidos ao teste do nado forçado. A administração de LY 235959, no IL ou PL, produziu efeitos do tipo antidepressivo, sendo esse efeito sensível ao tempo de administração da droga em relação à exposição ao nado forçado. Sendo assim, foi observado efeito antidepressivo quando o bloqueio glutamatérgico no PL ocorreu imediatamente após o nado ou antes da re-exposição ao estresse; enquanto no IL, o tratamento promoveu efeito antidepressivo apenas quando administrado antes da re-exposição ao nado. Portanto, os resultados sugerem que a neurotransmissão glutamatérgica mediada por receptores NMDA no CPFMv contribui para o desenvolvimento de consequências comportamentais do estresse, de modo que o bloqueio desses receptores facilitaria a adaptação ao estresse e induziria efeitos do tipo-antidepressivo. Os resultados sugerem, ainda, que o PL e o IL participam de maneira semelhante na modulação desses processos. / It is believed that high amounts of glutamate are related to the neurobiology of depression. Recent studies indicate that the amount of cortical glutamate is increased in depressed patients compared to healthy subjects. Among the cortical structures, the ventral medial prefrontal cortex (CPFMv), divided into infralimbic (IL) and prelimbic (PL) has been most often implicated in the development of mental disorders, such as depression. Considering that IL and PL play different roles on the emotional control in response to stress, this study was aimed to evaluate the hypothesis that the activation of glutamate NMDA receptors within the CPFMv, IL and PL, would facilitate the development of forced swimming-induced behavioral responses, an animal model predictive of antidepressants effects. To this end, we investigated the effects induced by the administration in the PL or the IL of LY 235959, an antagonist of NMDA receptors, at three different times, in animals submitted to the forced swimming test. The administration of LY 235959, in the IL or PL, produced antidepressant-like effects, and this effect is sensitive to moment of drug administration in relation to exposure to forced swimming. Thus, the antidepressant-like effect was observed when blocking the NMDA blockade into the PL occurred immediately after swimming or before re-exposure to stress, whereas in the IL, such treatment promoted antidepressant-like effect only when administered before re-exposure to swimming. Therefore, the results suggest that the glutamatergic neurotransmission mediated by NMDA receptors in the CPFMv contributes to the development of behavioral consequences of stress, so that blocking these receptors would facilitate the adaptation to stress and induce antidepressant-like effects. The results also suggest that PL and IL may be similarly involved in modulating these processes.

O envelhecimento da população mundial aumentou o interesse na busca pelos mecanismos fisiológicos e bioquímicos envolvidos no processo do envelhecimento saudável e por estratégias preventivas e terapêuticas de doenças relacionadas à idade. O envelhecimento cerebral alterou a atividade global de histona desacetilases (HDAC), enzima envolvida nos níveis de acetilação de histonas, marca epigenética relacionada com a expressão gênica. Nosso grupo de pesquisa demonstrou que o protocolo de exercício físico diário em esteira reduziu a atividade global da HDAC no córtex frontal imediatamente e 1 hora após a última sessão de treino. Assim, é de interesse elucidar as isoformas de HDAC envolvidas no processo de envelhecimento e no efeito do exercício físico. O exercício físico voluntário aumenta os níveis do Fator Neurotrófico Derivado do Encéfalo (BDNF) por mecanismos epigenéticos, no entanto, o impacto do exercício forçado parece ser contraditório. Nossos objetivos foram avaliar os efeitos do envelhecimento e do exercício de corrida sobre os níveis de HDAC2 e de BDNF em córtex pré-frontal de ratos Wistar. Para isso, utilizamos ratos Wistar machos com 3 e 20 meses de idade. Os animais do grupo exercitado foram submetidos ao protocolo diário de exercício físico moderado em esteira por 14 dias. No 13° dia, os animais foram submetidos à tarefa da esquiva inibitória (treino) e, no 14° dia, 30 minutos após a última sessão de exercício físico, foi realizado o teste do paradigma da esquiva inibitória. Após 30 minutos do teste na esquiva inibitória (uma hora após a última sessão de exercício), os córtices foram obtidos para os ensaios bioquímicos. Os níveis da HDAC2 foram maiores em córtices de animais envelhecidos. Ainda, foi observada uma correlação negativa entre o conteúdo da HDAC2 e o desempenho no teste de memória aversiva (esquiva inibitória). O exercício físico em esteira não alterou os níveis de HDAC2 em nenhuma das idades testadas. O envelhecimento e o exercício físico em esteira não alteraram os níveis de BDNF. Nossos dados sugerem que os altos níveis de HDAC2 estão envolvidos com o pior desempenho de animais envelhecidos na memória aversiva e que esta isoenzima não está relacionada aos efeitos epigenéticos do exercício físico em córtex pré-frontal. / Increasing attention has been paid to study the physiological and biochemical mechanisms of healthy aging process as well to seek therapeutic and protective strategies for age-related neurodegenerative diseases, since the aging population is growing. Epigenetic marks related to gene expression has been involved in aging brain process; increases in global histone desacetylase (HDAC) activity, enzyme involved with histone acetylation levels, has been found in aged brain areas. Our research group demonstrated that daily treadmill exercise protocol reduced global HDAC activity in frontal cortex immediately and 1hr after the last training session. The role of HDAC isoforms in aging process and exercise effects still needs to be elucidated. Taken that a specific HDAC isoform, HDAC2, has been involved with formation of hippocampus-dependent memory, the involvement of HDAC2 in aging process and exercise effects must be considered. Besides, it was described that voluntary exercise increases the levels of brain-derived neurotrophic factor (BDNF) through epigenetic mechanisms; while the forced exercise effects on BDNF levels seem be contradictory. Our aim was to evaluate the aging and exercise effects on HDAC2 and BDNF levels in prefrontal cortices of Wistar rats. Young adult and age male Wistar rats were submitted to a daily moderate treadmill exercise protocol (20 min/day during 14 days). The rats were assigned to sedentary and exercise groups. Single-trial step-down inhibitory avoidance (IA) conditioning was employed as an aversive memory paradigm. In the training trial (IA), rats were placed on a platform and immediately after stepping down on the grid received a footshock prior to removal from the apparatus. The test trial took place 24 hours after the training trial. Prefrontal cortices were obtained thirty minutes after inhibitory avoidance test, what was 1 hour after the last training session of exercise. HDAC2 levels were increased in cortices of aged rats. Moreover, a negative correlation was observed between HDAC2 content and aversive memory performance evaluated by inhibitory avoidance. Treadmill exercise did not alter the HDAC2 levels in any evaluated age. Aging process and treadmill exercise were unable to alter BDNF levels. Our results suggest that the age-related memory impairment may be associated with the increased HDAC2 levels.