Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2016-07-21T17:25:58Z No. of bitstreams: 1 AndreaLimaDeSa_TESE.pdf: 4573844 bytes, checksum: 9f1a31fbaa0a719d2f0fb7406f6aca31 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2016-07-22T12:47:11Z (GMT) No. of bitstreams: 1 AndreaLimaDeSa_TESE.pdf: 4573844 bytes, checksum: 9f1a31fbaa0a719d2f0fb7406f6aca31 (MD5) / Made available in DSpace on 2016-07-22T12:47:11Z (GMT). No. of bitstreams: 1 AndreaLimaDeSa_TESE.pdf: 4573844 bytes, checksum: 9f1a31fbaa0a719d2f0fb7406f6aca31 (MD5) Previous issue date: 2014-09-05 / O c?rtex somatosensorial prim?rio (S1), recebe informa??es dos receptores t?teis localizados na periferia sensorial e desempenha um papel crucial na explora??o ambiental. No entanto, essa regi?o do SNC adulto, como v?rias outras, apresenta uma redu??o expressiva no seu potencial pl?stico na fase adulta. Esse fato se deve ? presen?a de estruturas e subst?ncias que impedem a regenera??o dos neuritos ap?s a les?o, como por exemplo os componentes da matriz extracelular (MEC) presentes nas redes perineuronais. O amadurecimento das redes perineuronais (RPNs) coincide com o fechamento do per?odo cr?tico de plasticidade, pois os proteoglicanos da matriz extracelular atuam na estabiliza??o dos contatos sin?pticos. A remo??o dos componentes desta matriz ? uma manobra promissora para o restabelecimento da plasticidade e da recupera??o funcional de ?reas lesionadas do sistema nervoso central de animais adultos. Na presente tese, realizamos a remo??o das PGSCs do meio extracelular do c?rtex cerebral como terapia para restaurar a plasticidade e promover a regenera??o morfofuncional do c?rtex somest?sico prim?ria (SI) ap?s remo??o das vibrissas mistaciais durante o per?odo cr?tico. O tratamento com CABC mostrou-se eficaz para o estabelecimento de plasticidade cerebral com altera??es axonais, celulares e recupera??o funcional. / The primary somatosensory cortex (S1) receives inputs from peripheral tactile receptors and plays a crucial role on many important behaviors. However, the plastic potential of this region is greatly reduced during adulthood, limiting functional recovery after injuries. This fact is due to the presence, in the brain parenchima, of structures and substances that have an inhibitory effect on plasticity, such as chondroitin sulfate proteoglicans (CSP) present in the perineuronal.nets (PNNs) surrounding a subset of neurons. Maturation of PNNs coincide with the closure of critical periods of plasticity in cortical areas, since CSP act to stabilize synaptic contacts. Removal of CSP is proven to be an effective therapeutic approach to restore plasticity and increase the odds of functional recovery after cortical lesion. In the present work, we removed CSP from the sensorimotor cortex of rats to restore plasticity and promote the compensatory morphofunctional regeneration of cortical circuits modified by removal of mystacial vibrissae during the critical period. Treatment with the CSP-digesting enzyme chondroitinase ABC proved efficient to restore plasticity in S1 circuits, as evidenced by morphological rearrangements and functional recovery.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2016-12-29T19:00:45Z No. of bitstreams: 1 AndersonHenriqueFrancaFigueredoLeao_TESE.pdf: 9217812 bytes, checksum: cac2716089a2fdc3b21b756ad7ac5444 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2017-01-02T21:43:34Z (GMT) No. of bitstreams: 1 AndersonHenriqueFrancaFigueredoLeao_TESE.pdf: 9217812 bytes, checksum: cac2716089a2fdc3b21b756ad7ac5444 (MD5) / Made available in DSpace on 2017-01-02T21:43:34Z (GMT). No. of bitstreams: 1 AndersonHenriqueFrancaFigueredoLeao_TESE.pdf: 9217812 bytes, checksum: cac2716089a2fdc3b21b756ad7ac5444 (MD5) Previous issue date: 2016-05-06 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico (CNPq) / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES) / A Doen?a de Parkinson (DP) ? um dist?rbio motor relacionado ao envelhecimento que atualmente acomete de 1-2% da popula??o mundial acima dos 60 anos. No Brasil, estima-se que esta acometa aproximadamente 600 mil indiv?duos, configurando-se como uma enfermidade de import?ncia para pa?ses em processo de incremento da expectativa de vida. A epidemiologia da DP revela fatores de risco intr?nsecos e extr?nsecos ao paciente que definem a chance de desenvolvimento do dist?rbio. Muta??es pontuais e polimorfismos com significado funcional s?o tidos como fatores gen?ticos predisponentes, enquanto a exposi??o a pesticidas e toxinas destacam-se como fatores ambientais. No entanto, poucos estudos em modelos animais focam em investigar a intera??o entre estes fatores. Isto pode ser alcan?ado comparando-se os efeitos de subst?ncias indutoras de parkinsonismo em linhagens de ratos com diferentes contextos gen?ticos. Recentemente, o tratamento repetido com baixas doses de reserpina - um inibidor irrevers?vel do transportador vesicular de monoaminas (VMAT2) - foi proposto como um modelo progressivo para a DP. Sob este regime de tratamento, roedores apresentam, de forma progressiva, comprometimento motor, cognitivo, e altera??es neuroqu?micas compat?veis com a fisiopatologia da DP. Em paralelo, comparados a ratos Wistar, animais da linhagem SHR (Spontaneously Hypertensive Rats) s?o resistentes ? indu??o da discinesia oral pelo tratamento agudo com reserpina. Em vista destes achados, n?s buscamos avaliar se ratos SHR seriam resistentes aos d?ficits motores e altera??es neuroqu?micas quando submetidos ao modelo progressivo para DP induzido por reserpina. Portanto, n?s submetemos ratos Wistar e SHR ao tratamento agudo (1 mg/kg) ou repetido (15 inje??es de 0,1 mg/kg, em dias alternados) com reserpina e investigamos a progress?o dos d?ficits motores nas tarefas de catalepsia em barra, discinesia oral, e atividade espont?nea em campo aberto. Observamos ent?o que, para ambos os regimes de tratamento, animais SHR se mostram resilientes ao preju?zo motor em todas as dimens?es motoras avaliadas. Ainda, estas diferen?as se manifestaram tanto na lat?ncia para o surgimento do comprometimento motor como para a magnitude deste. Estas altera??es foram ainda acompanhadas por decr?scimo na express?o da tirosina hidroxilase (TH) e incremento na express?o de ?-sinucle?na na via nigro-estriatal de ambas linhagens submetidas ao tratamento com reserpina. Estas altera??es neuroqu?micas resultantes do tratamento com reserpina tamb?m se refletiram nos n?veis de monoaminas - dopamina e serotonina - na via nigro-estriatal destes animais. De modo geral, como no comportamento motor, animais SHR apresentaram atraso para a deple??o de monoaminas e menor magnitude deste efeito. Em conclus?o, os resultados aqui apresentados claramente corroboram a resili?ncia de ratos SHR ao modelo progressivo da DP. Estes achados exp?em novos alvos potenciais para as diferen?as neuroqu?micas, moleculares e gen?ticas na linhagem SHR relevantes para o estudo da susceptibilidade ? DP. / Parkinson?s disease (PD) is an aging-related progressive neurodegenerative disorder characterized by motor and non-motor symptoms, which affects 1-2% of the world population above 60 years old. In Brazil, this approximately 600 thousand people live with this disorder. Thus, PD is an important burden to countries with increasing life expectancy. The epidemiology of PD highlight intrinsic and extrinsic risk factors that are stochastic to the development of the disorder. Predisposing genetic factors comprise punctual mutations and polymorphisms with functional significance, while exposition to toxins is emphasizedas environmental factors. Nevertheless, few animal studies focus on the investigation of the interaction between these factors. Such may be accomplished by comparing the effects of substances that cause parkinsonism on rat strains with different genetic backgrounds. Recently, the repeated treatment with a low-dose of reserpine ? an irreversible inhibitor of the vesicular monoamine transporter (VMAT2) ? was suggested as a progressive model of PD. Rats under this treatment regimen show progressive catalepsy behavior, oral dyskinesia and spontaneous motor activity decrement. In parallel, compared to Wistar rats, SHR (Spontaneously Hypertensive Rat) are resistant to acute reserpine-induced oral dyskinesia. In view of these findings, we aimed to assess whether SHR would be resistant to repeated reserpine-induced motor and neurochemical deficits when submitted to the progressive model of PD. Thus, we submitted Wistar and SHR rats to the acute (1 mg/kg) or repeated (0,1 mg/kg, 15x, every other day) treatment with reserpine and investigated the progression of motor deficits in the catalepsy bar, oral dyskinesia, and spontaneous activity on the open field. Our results revealed that, for both treatment regimens, SHR rats were resistant to the motor impairment for all motor parameters assessed. Moreover, these differences were detected for both the latency to instauration and the magnitude of the impairment. The alterations were concomitant to a decrement in the optical density of tyrosine hydroxylase and an increment in ?-synuclein immunostaining by immunohistochemistryin the nigro-striatal pathway of both strains submitted to reserpine treatment. These neurochemical alterations resulted from reserpine treatment also reflected in the levels of monoamines ? dopamine and serotonin ? in the nigro-striatal pathway of these animals. Altogether, similarly to the motor behavior, SHR rats displayed lower magnitude and a delay to monoamine depletion. In conclusion, the current results clearly evidence the resilience of SHR to the repeated low-dose reserpine protocol. These findings uncover new potential underlying neurochemical, molecular and genetic differences in the SHR strain relevant to the study of susceptibility to PD.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2016-04-09T00:26:04Z No. of bitstreams: 1 StefanoPupeJohann_TESE.pdf: 36592987 bytes, checksum: f44357f3110776cf9f7cb628b2d65a95 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2016-04-09T00:36:11Z (GMT) No. of bitstreams: 1 StefanoPupeJohann_TESE.pdf: 36592987 bytes, checksum: f44357f3110776cf9f7cb628b2d65a95 (MD5) / Made available in DSpace on 2016-04-09T00:36:12Z (GMT). No. of bitstreams: 1 StefanoPupeJohann_TESE.pdf: 36592987 bytes, checksum: f44357f3110776cf9f7cb628b2d65a95 (MD5) Previous issue date: 2015-03-20 / Os neurocientistas tem uma diversidade de perspectivas com as quais podem classificar diferentes partes do c?rebro. Com o surgimento de t?cnicas baseadas na gen?tica, como a optogen?tica, se torna cada vez mais importante identificar se um grupo de c?lulas, definidas atrav?s de morfologia, fun??o ou posi??o anat?mica possui um padr?o caracter?stico de express?o de um ou mais promotores gen?ticos. Isso permitiria melhores formas de estudar essas popula??es de neur?nios definidas geneticamente. Neste trabalho, eu apresento uma discuss?o te?rica e tr?s estudos experimentais nos quais essa foi a principal quest?o sendo abordada. O Estudo I discute as quest?es envolvidas em selecionar um promotor para estudar estruturas e subpopula??es na ?rea Tegmental Ventral. O Estudo II caracteriza uma subpopula??o de c?lulas na ?rea Tegmental Ventral que compartilha a express?o de um promotor, que ? anatomicamente muito restrita, e que induz avers?o quando estimulada. O Estudo II utiliza uma estrat?gia similar para investigar a subpopula??o no n?cleo subtal?mico que expressa PITX2 e VGLUT2 que, quando inativada, causa hiperlocomo??o. O Estudo IV explora o fato de que um grupo de c?lulas previamente identificadas no Hipocampo Ventral expressa CHRNA2, e indica que essa subpopula??o pode ser necess?ria e suficiente para o estabelecimento do ritmo teta (2-8 Hz) no Hipocampo Ventral de camundongos anestesiados. Todos esses estudos foram guiados pela mesma estrat?gia de identificar um promotor gen?tico capaz de permitir o controle de uma popula??o de neur?nios identificada geneticamente, e eles demonstram as diferentes formas em que essa abordagem pode generar novas descobertas. / Neuroscientists have a variety of perspectives with which to classify different parts of the brain. With the rise of genetic-based techniques such as optogenetics, it is increasingly important to identify whether a group of cells, defined by morphology, function or anatomical location possesses a distinct pattern of expression of one or more genetic promoters. This would allow for better ways to study of these genetically defined subpopulations of neurons. In this work, I present a theoretical discussion and threeexperimental studies in which this was the main question being addressed. Paper I discusses the issues involved in selecting a promoter to study structures and subpopulations in the Ventral Tegmental Area. Paper II characterizes a subpopulation of cells in the Ventral Tegmental Area that shares the expression of a promoter and is anatomically very restricted, and induces aversion when stimulated. Paper III utilizes a similar strategy to investigate a subpopulation in the subthalamic nucleus that expresses PITX2 and VGLUT2 which, when inactivated, causes hyperlocomotion. Paper IV exploits the fact that a previously identified group of cells in the ventral hippocampus expresses CHRNA2, and indicates that this population may be necessary and sufficient for the establishment of the theta rhythm (2-8 Hz) in the Local Field Potential of anesthetized mice. All of these studies were guided by the same strategy of characterizing and studying the role of a genetically defined subpopulation of cells, and they demonstrate the different ways in which this approach can generate new discoveries.

Submitted by PPG Educa??o em Ci?ncias e Matem?tica (educem-pg@pucrs.br) on 2018-06-13T17:58:16Z No. of bitstreams: 1 DISSERTA??O VERS?O FINALISSIMA-estrella-thomaz-homologada-12-06-18.pdf: 2016860 bytes, checksum: 3d63ade2916682d8d1d05ed6dec28dfd (MD5) / Approved for entry into archive by Sheila Dias (sheila.dias@pucrs.br) on 2018-06-25T12:31:19Z (GMT) No. of bitstreams: 1 DISSERTA??O VERS?O FINALISSIMA-estrella-thomaz-homologada-12-06-18.pdf: 2016860 bytes, checksum: 3d63ade2916682d8d1d05ed6dec28dfd (MD5) / Made available in DSpace on 2018-06-25T12:49:06Z (GMT). No. of bitstreams: 1 DISSERTA??O VERS?O FINALISSIMA-estrella-thomaz-homologada-12-06-18.pdf: 2016860 bytes, checksum: 3d63ade2916682d8d1d05ed6dec28dfd (MD5) Previous issue date: 2018-03-14 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / In the last decade, the advance of Cognitive Neuroscience has been well-known, conceptualizing new understandings about the different cognitive processes that support teaching and learning processes. In this sense, knowing an opinion of teachers and graduates about such knowledge becomes relevant and necessary for those who work in the classroom. Thus, the research reported in this dissertation presents some answers to the following question: How do Basic Education teachers in the area of Natural Sciences and Biology, Physics and Chemistry graduates prepare for teaching and teaching from the perspective of Cognitive Neuroscience and how do they value these assumptions in their teaching practice? A data collection through the application of questions to 13 teachers of Basic Education and 20 students of undergraduate courses in the area of Natural Sciences, all of them are interviewed, with audio recording. With perspectives as participant perceptions, as answers and analyzes through Discursive Textual Analysis - ATD, allowing a conclusion to be obtain. The lack of interaction between neuroscientists and professionals in the field of education implies information and, consequently, lack of applicability of the consolidated results not Brazil and in other countries, even if they are documented researched values such concepts. From the analysis of the collected data, it is highlighted that, despite the low utilization of the knowledge of Cognitive Neuroscience in the classroom, there is great enthusiasm on the part of the participants, a respect to the use of knowledge. The results also show the existence of neuromyths in the teaching field, which may result in inadequate teaching approaches, in real time in data without scientific criteria. Thus, there is a need to train teachers in reference to brain functioning, associated with learning situations, in order to expand studies with scientific bases, which may contribute to a qualification of non-country education. Thus, there is a space to be filled between the neuroscientist who studies learning, the teacher of Basic Education and a training of teachers of Higher Education. / Na ?ltima d?cada, tem sido not?rio o avan?o da Neuroci?ncia Cognitiva, fornecendo novos entendimentos sobre os diferentes processos cognitivos que d?o suporte aos processos de ensino e de aprendizagem. Nesse sentido, conhecer a opini?o de professores e licenciandos sobre tais conhecimentos, torna-se relevante e necess?rio para quem atua em sala de aula. Assim, a pesquisa relatada nesta disserta??o apresenta algumas respostas ao seguinte questionamento: De que modo professores da Educa??o B?sica, da ?rea de Ci?ncias da Natureza e licenciandos de Biologia, F?sica e Qu?mica, est?o preparados para tratar do ensino e da aprendizagem na perspectiva da Neuroci?ncia Cognitiva e como valorizam esses pressupostos na sua pr?tica docente? A coleta de dados ocorreu por meio da aplica??o de question?rios a 13 professores da Educa??o B?sica e a 20 estudantes de cursos de licenciaturas da ?rea de Ci?ncias da Natureza, que tamb?m foram entrevistados, com grava??o em ?udio. Com vistas a compreender as percep??es dos participantes, as respostas foram analisadas por meio da An?lise Textual Discursiva ? ATD, permitindo a obten??o das conclus?es a seguir. A falta de intera??o entre cientistas da ?rea neuroci?ncias e profissionais da ?rea do ensino implica car?ncia de informa??es e, consequentemente, falta de aplicabilidade dos resultados consolidados no Brasil e em outros pa?ses, mesmo que os docentes pesquisados valorizem tais conceitos. A partir da an?lise dos dados coletados, destaca-se que, apesar da pouca utiliza??o dos conhecimentos provenientes da Neuroci?ncia Cognitiva em sala de aula, h? grande entusiasmo por parte dos participantes, a respeito da utiliza??o de tais conhecimentos. Os resultados tamb?m mostram a exist?ncia de neuromitos no ?mbito docente, podendo resultar em abordagens inadequadas de ensino, baseada em dados sem crit?rio cient?fico. Surge, assim, a necessidades de melhorar a forma??o de professores em assuntos referentes ao funcionamento cerebral, associados a situa??es de aprendizagem, de modo a ampliar os estudos com bases cient?ficas, o que pode contribuir para a qualifica??o da educa??o no pa?s. Portanto, existe um espa?o a ser preenchido entre o neurocientista que estuda aprendizagem, o professor da Educa??o B?sica e a forma??o de professores no Ensino Superior.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2017-11-03T20:50:56Z No. of bitstreams: 1 JessicaDeAndradePessoa_DISSERT.pdf: 10020769 bytes, checksum: daeec5fd94bc7d6846a49b3d22ead059 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2017-11-17T19:54:39Z (GMT) No. of bitstreams: 1 JessicaDeAndradePessoa_DISSERT.pdf: 10020769 bytes, checksum: daeec5fd94bc7d6846a49b3d22ead059 (MD5) / Made available in DSpace on 2017-11-17T19:54:39Z (GMT). No. of bitstreams: 1 JessicaDeAndradePessoa_DISSERT.pdf: 10020769 bytes, checksum: daeec5fd94bc7d6846a49b3d22ead059 (MD5) Previous issue date: 2017-07-27 / A ayahuasca ? uma bebida com propriedades psicod?licas amplamente utilizada por popula??es ind?genas da regi?o amaz?nica. Esse preparo cont?m a triptamina psicod?lica N,N-dimetiltriptamina (DMT), e inibidores da monoamina oxidase (iMAO), como harmina e harmalina. A ayahuasca ? considerada um psicod?lico seroton?rgico, e que pode levar a um estado alterado de consci?ncia com semelhan?as a uma experi?ncia on?rica, com intensas altera??es na percep??o, pensamentos, humor, emo??o, e experi?ncias tidas como m?sticas. Correlatos neurais dos efeitos agudos da ayahuasca t?m sido investigados por diferentes t?cnicas de neuroimagem funcional, incluindo a eletroencefalografia (EEG). Neste trabalho exploramos mudan?as espectrais de EEG em 50 volunt?rios saud?veis, utilizando desenho randomizado duplo-cego placebo-controlado. Metade recebeu uma sess?o com a ayahuasca, a outra metade com placebo. Ap?s a administra??o da subst?ncia, os volunt?rios foram monitorados durante 4 horas por um equipamento de EEG. A fim de melhorar a qualidade dos dados, os volunt?rios foram solicitados a realizar 2 tarefas simples em tr?s instantes espec?ficos: antes da ingest?o, 2h e 4 horas ap?s a ingest?o. Na primeira tarefa, deveriam tentar permanecer acordados, e intercalar per?odos de 20 segundos de olhos abertos, e 40 segundos de olhos fechados, durante 5 minutos. Na segunda tarefa, eles deveriam permanecer de olhos fechados, tentando se manter acordados, por outros 5 minutos. A an?lise espectral (2h) revelou que a pot?ncia de alfa ? significativamente menor no grupo ayahuasca que no placebo nas regi?es occipital e temporoparietal ? direita. Encontramos, ainda, aumento significativo em 2h na pot?ncia de teta na regi?o temporoparietal ? direita. A an?lise de correla??o revelou correspond?ncias entre a pot?ncia de alfa (2h) e a pontua??o obtida em duas escalas sens?veis aos efeitos de psicod?licos - a Hallucinogen Rating Scale (HRS) e o Mystical Experience Questionnaire (MEQ). Apresentamos, ainda, achados de tra?ados curiosos, encontrados na inspe??o visual dos tra?ados de EEG. De modo geral, nossos resultados sugerem que a inibi??o das oscila??es alfa em regi?es posteriores do c?rebro desempenha papel importante na experi?ncia psicod?lica, talvez compartilhando mecanismos presentes durante a experi?ncia on?rica. / Ayahuasca is a brew with psychedelic properties largely used by indigenous populations from the Amazon basin. It contains the psychedelic tryptamine N,N-dimethyltriptamine (DMT), and monoamine oxidase inhibitors (iMAO), such as harmine and harmaline. Ayahuasca is consid-ered to be a serotonergic psychedelic, capable of inducing an altered state of consciousness with similarities to an oneiric experience, with intense alterations in perception, though, humor, emo-tion, and mystical-type experiences. The neural correlates of its acute effects have been inves-tigated by different neuroimaging techniques, including electroencephalography (EEG). In this study, we explored EEG spectral changes in 48 healthy volunteers using a randomized double-blind placebo-controlled trial. Half of the volunteers received ayahuasca, half received placebo. We used an EEG system to monitor all volunteers throughout the dosing session, which lasted approximately 4-hours. Aiming to improve data quality, the volunteers were asked to perform two controlled tasks at three specific moments: before intake, 2h and 4h after intake. For the first task, they alternated moments of eyes open (20 seconds) with eyes closed (40 seconds) for 5 minutes, avoiding falling asleep. During the second task they should keep their eyes closed for another 5 minutes, again avoiding falling asleep. Spectral analysis at 2h after intake shows reduced alpha power, and increased theta and beta in the ayahuasca group with respect to the placebo, mainly in occipital and right temporoparietal regions. Correlation analysis revealed correspondences between the alpha power (2h) and individual scores on two scales used to measure psychedelic effects ? the Hallucinogen Rating Scale (HRS) and the Mystical Experi-ence Questionnaire (MEQ). Additionally, we also present EEG traces with electrophysiological events that might be of importance for the representation of the psychedelic experience. Over-all, our results suggest that the inhibition of alpha oscillations, increased theta and beta in right posterior brain regions play an important role on the psychedelic experience, maybe sharing mechanisms present during the oneiric experience.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2018-01-16T18:01:47Z No. of bitstreams: 1 KatiaSimoneDeAraujoNobregaRocha_DISSERT.pdf: 15764760 bytes, checksum: 8bfb9a0320607958c4f488fa38d6706c (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2018-01-22T11:31:34Z (GMT) No. of bitstreams: 1 KatiaSimoneDeAraujoNobregaRocha_DISSERT.pdf: 15764760 bytes, checksum: 8bfb9a0320607958c4f488fa38d6706c (MD5) / Made available in DSpace on 2018-01-22T11:31:34Z (GMT). No. of bitstreams: 1 KatiaSimoneDeAraujoNobregaRocha_DISSERT.pdf: 15764760 bytes, checksum: 8bfb9a0320607958c4f488fa38d6706c (MD5) Previous issue date: 2017-08-31 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES) / Cortical gamma oscillations (30 - 90 Hz) have been implicated in various cognitive processes, such as perceptual binding and attention. So far, most evidence in support of this hypothesis is based on studies that used artificial and simplified stimuli, such as moving gratings and bars. Recently, experimental work using natural images led to conflicting conclusions. In a paradigm that required human subjects to maintain fixation, electrocorticogram signals (ECoG) showed gamma for grating stimuli but not for static images or pink noise (Hermes et al., 2015). On the contrary, analysis of ECoG in the early visual cortex of macaque monkeys revealed strong gamma components for free viewing of natural scenes (Brunet et al., 2015). Here, we aim to clarify these discrepancies using a paradigm that allowed direct comparisons between fixation vs. free viewing conditions, for both simplified stimuli (moving and static gratings) and natural scenes (static and moving images). Recordings of spiking activity and local field potentials (LFPs) were obtained from the central and the peripheral representations of V1. Our results show that in capuchins (N= 3 monkeys), as previously described in macaques and humans, gamma is characteristically strong when stimulus parameters, such as size, orientation, and speed are set at to optimal values. Comparisons between fixation vs. free viewing conditions and gratings vs. natural stimuli revealed that gamma is always high for optimal grating stimuli, regardless of viewing condition (N= 93 recording sites, 2 monkeys). However, gamma is surprisingly absent during free viewing of natural images and movies. Similar negative findings were also obtained when the monkeys were exposed to real-world scenes, such as objects and other animals in the laboratory. The present results suggest that strong, narrow-band, gamma responses in V1 are primarily associated with the selective activation of cell populations sharing similar response properties. Therefore, gamma may be seen as a resonance phenomenon of the underlying cortical connectivity. Overall, our results belittle the importance of gamma as a critical cortical mechanism for vision. / As oscila??es corticais gama (30 - 90 Hz) t?m sido implicadas em processos cognitivos como a liga??o perceptual e a aten??o. At? agora, a maioria das evid?ncias que servem de suporte para esta hip?tese ? baseada em e s t u d o s a p a r t i r do uso de e s t ? m u l o s s i m p l e s e artificiais, como grades e barras luminosas. Recentemente, no entanto, estudos experimentais utilizando imagens naturais levaram a conclus?es conflitantes. Em um paradigma em humanos que requeria fixa??o mantida, sinais eletrocorticogr?ficos (ECoG) mostraram gama para grades, mas n?o p a r a imagens e s t ? t i c a s ou r u ? d o r o s a (Hermes e t a l . , 2 0 1 5 ) . Contrariamente, a an?lise dos sinais ECoG no c?rtex visual de macacosreso revelou fortes componentes gama para a livre observa??o de cenas naturais (Brunet et al., 2015). Neste estudo, temos por objetivo esclarecer essas discrep?ncias utilizando-se de um paradigma que permitiu compara??es diretas entre uma condi??o de fixa??o vs. uma condi??o de observa??o livre, tanto para est?mulos simplificados (grades m?veis e e s t ? t i c a s ) q u a n t o p a r a c e n a s n a t u r a i s ( i m a g e n s e s t ? t i c a s e em movimento). Registros de potenciais de a??o e de potenciais de campo locais (LFPs) foram obtidos para a representa??o central e perif?rica de V1. Nossos resultados demonstram que em macacos-capuchinhos (N = 3), como descrito anteriormente para macacos-reso e humanos, a gama ? caracteristicamente forte, sempre que os par?metros do est?mulo, como tamanho, orienta??o e velocidade, s?o definidos para a ativa??o ?tima das c?lulas. Compara??es entre condi??es de fixa??o e de livre observa??o e grades vs. est?mulos naturais revelaram que a gama ? sempre forte para grades de orienta??o ?tima, independentemente da condi??o de visualiza??o (N = 93 s?tios de registro, 2 macacos). No entanto, a gama est? surpreendentemente ausente durante a livre visualiza??o de imagens e filmes naturais. Achados negativos semelhantes tamb?m foram obtidos quando os macacos foram expostos a cenas do mundo real, como objetos e outros animais no laborat?rio. Os presentes resultados sugerem que, no c?rtex visual prim?rio, a atividade gama ? principalmente associada ? ativa??o seletiva de popula??es neuronais que compartilham propriedades de resposta similares. Portanto, a gama pode ser vista como um fen?meno de resson?ncia da conectividade cortical subjacente. Em geral, nossos resultados minimizam a import?ncia da gama como um mecanismo cortical chave para a vis?o.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2016-08-16T23:02:45Z No. of bitstreams: 1 AnaMariaAraujoSoares_DISSERT.pdf: 3132164 bytes, checksum: 1d26fedd574b389db008072f0a9d4fcb (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2016-08-24T00:27:46Z (GMT) No. of bitstreams: 1 AnaMariaAraujoSoares_DISSERT.pdf: 3132164 bytes, checksum: 1d26fedd574b389db008072f0a9d4fcb (MD5) / Made available in DSpace on 2016-08-24T00:27:46Z (GMT). No. of bitstreams: 1 AnaMariaAraujoSoares_DISSERT.pdf: 3132164 bytes, checksum: 1d26fedd574b389db008072f0a9d4fcb (MD5) Previous issue date: 2015-10-30 / O autismo ? um transtorno do desenvolvimento que se manifesta nos primeiros anos de vida e apresenta semiologia heterog?nea. Esta patologia afeta a matura??o do enc?falo e produz altera??es sensoriais, de linguagem e de intera??o social no in?cio na inf?ncia. O modelo experimental de autismo utilizando ?cido valproico (VPA) durante o per?odo gestacional tem sido demonstrado ter alta validade de face e permitir estudos tanto das bases neuropatol?gicas quanto neuro-funcionais durante o desenvolvimento. A despeito do recente interesse por este modelo como instrumento de compreens?o dos aspectos b?sicos da fisiopatologia do autismo, a maioria dos estudos experimentais t?m se concentrado nos aspectos comportamentais, histol?gicos e celulares. Neste trabalho, foram propostas estrat?gias experimentais de avalia??o comportamental associadas a eletrofisiologia \textit{in vivo}, uma t?cnica que nunca fora utilizada para avalia??o desse modelo. Animais controles e experimentais, submetidos previamente a um procedimento cir?rgico para implante de eletrodos cr?nicos, participaram de experimentos de livre explora??o, intera??o social e condicionamento ao medo. / O autismo ? um transtorno do desenvolvimento que se manifesta nos primeiros anos de vida e apresenta semiologia heterog?nea. Esta patologia afeta a matura??o do enc?falo e produz altera??es sensoriais, de linguagem e de intera??o social no in?cio na inf?ncia. O modelo experimental de autismo utilizando ?cido valproico (VPA) durante o per?odo gestacional tem sido demonstrado ter alta validade de face e permitir estudos tanto das bases neuropatol?gicas quanto neuro-funcionais durante o desenvolvimento. A despeito do recente interesse por este modelo como instrumento de compreens?o dos aspectos b?sicos da fisiopatologia do autismo, a maioria dos estudos experimentais t?m se concentrado nos aspectos comportamentais, histol?gicos e celulares. Neste trabalho, foram propostas estrat?gias experimentais de avalia??o comportamental associadas a eletrofisiologia \textit{in vivo}, uma t?cnica que nunca fora utilizada para avalia??o desse modelo. Animais controles e experimentais, submetidos previamente a um procedimento cir?rgico para implante de eletrodos cr?nicos, participaram de experimentos de livre explora??o, intera??o social e condicionamento ao medo.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2016-08-25T20:54:16Z No. of bitstreams: 1 MalekChouchane_TESE.pdf: 3043835 bytes, checksum: b90ef34a2d4072ef5abda48d216aebb4 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2016-08-26T21:40:31Z (GMT) No. of bitstreams: 1 MalekChouchane_TESE.pdf: 3043835 bytes, checksum: b90ef34a2d4072ef5abda48d216aebb4 (MD5) / Made available in DSpace on 2016-08-26T21:40:31Z (GMT). No. of bitstreams: 1 MalekChouchane_TESE.pdf: 3043835 bytes, checksum: b90ef34a2d4072ef5abda48d216aebb4 (MD5) Previous issue date: 2016-02-29 / Recently, the field of cellular reprogramming has been revolutionized by works showing the potential to directly lineage-reprogram somatic cells into neurons upon overexpression of specific transcription factors. This technique offers a promising strategy to study the molecular mechanisms of neuronal specification, identify potential therapeutic targets for neurological diseases and eventually repair the central nervous system damaged by neurological conditions. Notably, studies with cortical astroglia revealed the high potential of these cells to reprogram into neurons using a single neuronal transcription factor. However, it remains unknown whether astroglia isolated from different regions of the central nervous system have the same neurogenic potential and generate induced neurons (iN) with similar phenotypes. Similarly, little is known about the fate that iNs could adopt after transplantation in the brain of host animals. In this study we compare the potential to reprogram astroglial cells isolated from the postnatal cerebral cortex and cerebellum into iNs both in vitro and in vivo using the proneural transcription factors Neurogenin-2 (Neurog2) and Achaete scute homolog-1 (Ascl1). Our results indicate cerebellar astroglia can be reprogrammed into induced neurons (iNs) with similar efficiencies to cerebral cortex astroglia. Notably however, while iNs in vitro adopt fates reminiscent of cortical or cerebellar neurons depending on the astroglial population used for reprogramming, in situ, after transplantation in the postnatal and adult mouse brain, iNs adopt fates compatible with the region of integration. Thus, our data suggest that the origin of the astroglial population used for lineage-reprogramming affects the fate of iNs in vitro, but this imprinting can be overridden by environmental cues after grafting.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2016-04-01T19:13:13Z No. of bitstreams: 1 JoseHenriqueTarginoDiasGois_DISSERT.pdf: 8111349 bytes, checksum: df4a2a7f9ab95c60e4e75a96288b99f9 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2016-04-06T00:26:58Z (GMT) No. of bitstreams: 1 JoseHenriqueTarginoDiasGois_DISSERT.pdf: 8111349 bytes, checksum: df4a2a7f9ab95c60e4e75a96288b99f9 (MD5) / Made available in DSpace on 2016-04-06T00:26:58Z (GMT). No. of bitstreams: 1 JoseHenriqueTarginoDiasGois_DISSERT.pdf: 8111349 bytes, checksum: df4a2a7f9ab95c60e4e75a96288b99f9 (MD5) Previous issue date: 2015-02-24 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico - CNPq / A administra??o de nicotina em seres humanos e roedores ? pensada como um melhorador de mem?ria e aten??o, tamb?m pelo seu efeito positivo na Doen?a de Alzheimer. O complexo do Septo Medial / Banda Diagonal de Broca (MS/DBB) ? um dos principais sistemas colin?rgicos ? massivamente projetado para o hipocampo atrav?s da F?mbria-F?rnix, via esta chamada de via septo-hipocampal. Foi demonstrado que o MS/DBB afeta diretamente o potencial de campo local (LFP) e a organiza??o r?tmica do hipocampo, especialmente na gera??o do ritmo teta - um LFP r?tmico intrinsecamente relacionado com a fun??o mnem?nica do hipocampo. Experimentos in vitro deram evid?ncias de que a nicotina aplicada no MS/DBB pode gerar um ritmo teta na rede local do MS/DBB. Assim, o presente estudo se prop?e a elucidar a fun??o da nicotina no MS/DBB sobre a via septo-hipocampal. Experimentos in vivo, comparando o efeito de microinfus?es no MS/DBB de solu??o salina (n = 5) ou nicotina (n = 8) em camundongos anestesiados por ketamina/xilazina mostraram um aumento na densidade de pot?ncia no espectro banda de gama (35 a 55 Hz) em ambas as estruturas (teste de Wilcoxon Rank-Sum, p = 0,038), mas sem alterar a coer?ncia entre as estruturas na mesma banda (teste de Wilcoxon Rank-Sum, p = 0,60). Houve tamb?m uma diminui??o na densidade pot?ncia na banda delta (1-3 Hz) ? oscila??o induzida pela ketamina. Realizamos tamb?m experimentos in vitro sobre o efeito da nicotina na voltagem de membrana e no potencial de a??o de neur?nios do MS/DBB. Registramos neur?nios (n=22) em current-clamp antes e depois da presen?a de nicotina no meio extracellular; 12 neur?nios responderam ? nicotina, metade aumentou a taxa de potenciais de a??o; outros seis diminu?ram, diferindo significativamente no limiar do potencial de a??o (- 47,3 ? 0,9 mV vs. -41 ? 1,9 mV, respectivamente, p = 0,007) e na largura do disparo (1,6 ? 0,08 vs. 2 ms ? 0,12 ms, respectivamente, p = 0,01). Al?m disso, realizamos outro conjunto de experimentos in vitro, relativo ? conectividade das tr?s grandes popula??es neuronais de MS / DBB que usam a acetilcolina, GABA ou glutamato como neurotransmissores. O registro pareado de patch-clamp mostrou que neur?nios glutamat?rgicos e GABA?rgicos realizam contatos intra-septais capazes de produzir correntes sin?pticas em neur?nios p?s-sin?pticos do MS/DBB. A probabilidade da conectividade entre diferentes popula??es neuronais foi implementada em um modelo realista que corrobora que a rede ? altamente sens?vel ? gera??o de ritmo gama. Juntamente com os dados dispon?veis, o conjunto completo de experi?ncias corrobora que a nicotina pode atuar como potenciador cognitivo, e um substrato eletrofisiol?gico prov?vel ? atrav?s da indu??o de oscila??o gama no circuito local do MS/DBB. / Nicotine administration in humans and rodents enhances memory and attention, and also has a positive effect in Alzheimer's Disease. The Medial Septum / Diagonal Band of Broca complex (MS/DBB) ? a main cholinergic system ? massively projects to the hippocampus through the fimbria-fornix, and this pathway is called the septohippocampal pathway. It has been demonstrated that the MS/DBB acts directly on the local field potential (LFP) rhythmic organization of the hippocampus, especially in the rhythmogenesis of Theta (4-8Hz) ? an oscillation intrinsically linked to hippocampus mnemonic function. In vitro experiments gave evidence that nicotine applied to the MS/DBB generates a local network Theta rhythm within the MS/DBB. Thus, the present study proposes to elucidate the function of nicotine in the MS/DBB on the septo-hippocampal pathway. In vivo experiments compared the effect of MS/DBB microinfusion of saline (n=5) and nicotine (n=8) on Ketamine/Xylazine anaesthetized mice. We observed power spectrum density in the Gamma range (35 to 55 Hz) increasing in both structures (Wilcoxon Rank-Sum test, p=0.038) but with no change in coherence between these structures in the same range (Wilcoxon Rank-Sum test, p=0.60). There was also a decrease in power of the ketamineinduced Delta oscillation (1 to 3 Hz). We also performed in vitro experiments on the effect of nicotine on membrane voltage and action potential. We patch-clamped 22 neurons in current-clamp mode; 12 neurons were responsive to nicotine, half of them increased firing rate and other 6 decreased, and they significantly differed in action potential threshold (-47.3?0.9 mV vs. -41?1.9 mV, respectively, p=0.007) and halfwidth time (1.6?0.08 ms vs. 2?0.12 ms, respectively, p=0.01). Furthermore, we performed another set of in vitro experiments concerning the connectivity of the three major neuronal populations of MS/DBB that use acetylcholine, GABA or glutamate as neurotransmitter. Paired patch-clamp recordings found that glutamatergic and GABAergic neurons realize intra-septal connections that produce sizable currents in MS/DBB postsynaptic neurons. The probability of connectivity between different neuronal populations gave rise to a MS/DBB topology that was implemented in a realistic model, which corroborates that the network is highly sensitive to the generation of Gamma rhythm. Together, the data available in the full set of experiments suggests that nicotine may act as a cognitive enhancer, by inducing gamma oscillation in the local circuitry of the MS/DBB.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2016-04-26T20:08:35Z No. of bitstreams: 1 ThawannMalfattiBorges_DISSERT.pdf: 27333324 bytes, checksum: 7928d876effa4fd0184f0b246ecd1c34 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2016-04-29T20:35:41Z (GMT) No. of bitstreams: 1 ThawannMalfattiBorges_DISSERT.pdf: 27333324 bytes, checksum: 7928d876effa4fd0184f0b246ecd1c34 (MD5) / Made available in DSpace on 2016-04-29T20:35:41Z (GMT). No. of bitstreams: 1 ThawannMalfattiBorges_DISSERT.pdf: 27333324 bytes, checksum: 7928d876effa4fd0184f0b246ecd1c34 (MD5) Previous issue date: 2015-06-26 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES) / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico (CNPq) / Tinnitus is the perception of a sound in the absence of a corresponding physical stimulus. It is not clear yet what mechanisms are involved in tinnitus and how it starts and/or becomes chronic. Due to the relationship between tinnitus and somatosensory trauma/stimuli, the dorsal cochlear nucleus (DCN), a region known to integrate somatosensory and auditory pathways, has been identified as a potential key structure in the generation of phantom sound perception. Here, we target specific neuronal populations in the DCN to allow further investigation on how this region may contribute to the generation of tinnitus signals that spread to other auditory areas. We examined the expression of optogenetic proteins (Channelrhodopsin 2 - ChR2; and enhanced Archaerhodopsin 3.0 - eArch3.0), targeting neurons expressing Calmoduline Kinase II alpha (CaMKIIa) promoter in wild-type C57/Bl6 mice and neurons expressing nicotinic acetylcholine receptor subunit alpha-2 promoter (ChRNA2) in ChRNA2- Cre transgenic C57/Bl6 mice, using local virus injection, verified by fluorescence microscopy. Unit responses were differentiated based on their electrophysiological response to sound. We then investigated if firing of neurons expressing optogenetic tools can be controlled in vivo and if the same neurons also fire action potentials in response to precisely timed sound stimulation. Both in vivo and preliminary in vitro data shows that neurons expressing ChR2 do respond to sound, and that they furthermore also can respond to light stimulation with a stable and similar waveform. Moreover, in vivo data shows that neurons expressing eArch3.0, responding to sound, will decrease their firing rate when exposed to green light. Thereby showing that optogenetic tools can be used functionally in the DCN, it is possible to further test tinnitus theories by, for example, producing an increased firing rate in the DCN, trying to mimic tinnitus; or inhibiting increased spontaneous firing rate in the DCN of animals with noise-induced or salycilate-induced tinnitus.