Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2016-03-10T21:38:12Z No. of bitstreams: 1 LuanaGabrielleDeFrancaFerreira_DISSERT.pdf: 3743895 bytes, checksum: 6586155eff1318ab76c3be9fd110f030 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2016-03-17T22:48:47Z (GMT) No. of bitstreams: 1 LuanaGabrielleDeFrancaFerreira_DISSERT.pdf: 3743895 bytes, checksum: 6586155eff1318ab76c3be9fd110f030 (MD5) / Made available in DSpace on 2016-03-17T22:48:47Z (GMT). No. of bitstreams: 1 LuanaGabrielleDeFrancaFerreira_DISSERT.pdf: 3743895 bytes, checksum: 6586155eff1318ab76c3be9fd110f030 (MD5) Previous issue date: 2015-04-10 / Diversos estudos revelam que nas ?ltimas d?cadas ocorreu uma diminui??o na dura??o do sono. Os compromissos sociais, como o trabalho e a escola, muitas vezes n?o est?o alinhados ao ?tempo biol?gico? dos indiv?duos. Somada a isso, observa-se uma menor for?a do zeitgeber causada pela menor exposi??o ? luz durante o dia e maior ? noite. Isso gera um d?bito cr?nico de sono que ? compensado nos dias livres, ocorrendo semanalmente uma restri??o e extens?o do sono denominada de jet lag social. A priva??o de sono vem sendo associada ? obesidade, risco cancer?geno e cardiovascular. Desta-forma, sugere-se que o sistema nervoso auton?mico seja um caminho que relaciona os problemas do sono ?s doen?as cardiovasculares. No entanto, al?m das evid?ncias demonstradas por pesquisas com uso de modelos de priva??o de sono de forma aguda e controlada, s?o necess?rios estudos investigando efeitos da priva??o do sono de forma cr?nica como ocorre no jet lag social. O objetivo deste estudo foi investigar a influ?ncia do jet lag social em marcadores circadianos de atividade-repouso e card?acos em estudantes do Curso de Medicina. Trata-se de um estudo transversal e observacional realizado no Laborat?rio de Neurobiologia e Ritmicidade Biol?gica (LNRB) do Departamento de Fisiologia da UFRN. Participaram da pesquisa estudantes de medicina matriculados no 1? per?odo do curso da UFRN. Foram utilizados os seguintes instrumentos: Question?rio cronotipo de Munique (MCTQ); Question?rio para identifica??o de indiv?duos matutinos e vespertinos (MEQ ou HO); ?ndice de qualidade do sono de Pittsburgh; Escala de Sonol?ncia de Epworth; Act?metro; Cardiofrequenc?metro. Foram analisadas vari?veis de caracteriza??o do sono, n?o param?tricas (IV60, IS60, L5 e M10) e ?ndices card?acos no dom?nio do tempo, frequ?ncia (LF, HF, LF/HF) e n?o linear (SD1, SD2, SD1/SD2). Realizou-se an?lise estat?stica descritiva, comparativa e de correla??o com uso do programa SPSS vers?o 20. Participaram do estudo 41 estudantes, 48,8% (20) mulheres e 51,2% (21) homens, com 19,63 ? 2,07 anos. O jet lag social teve uma m?dia de 02:39h ? 00:55h, 82,9% (34) com jet lag social ? 1 hora e houve correla??o negativa com escore cronotipo de Munique evidenciando maior priva??o do sono em indiv?duos com tend?ncia ? vespertinidade. Qualidade do sono ruim foi detectada em 90,2% (37) (X 2 = 26,56, p < 0,001) e 56,1% (23) sonol?ncia diurna excessiva (X 2 = 0,61, p = 0,435). Observou-se diferen?a significativa dos valores de LFnu, HFnu e LF/HF entre os grupos de jet lag social < 2h e ? 2h e houve correla??o do jet lag social com LFnu (rs = 0,354, p = 0,023), HFnu (rs = - 0,354, p = 0,023) e LF/HF (rs = 0,355, p = 0,023). Verificou-se ainda associa??o negativa entre IV60 e ?ndices no dom?nio do tempo e n?o lineares. Sugere-se que a priva??o cr?nica de sono pode ter associa??o com maior atividade simp?tica promovendo aumento no risco cardiovascular. / Studies reveal that in recent decades a decrease in sleep duration has occurred. Social commitments, such as work and school are often not aligned to the "biological time" of individuals. Added to this, there is a reduced force of zeitgeber caused by less exposure to daylight and larger exposure to evenings. This causes a chronic sleep debt that is offset in a free days. Indeed, a restriction and extent of sleep called "social Jet lag" occurs weekly. Sleep deprivation has been associated to obesity, cancer, and cardiovascular risk. It is suggested that the autonomic nervous system is a pathway that connects sleep problems to cardiovascular diseases. However, beyond the evidence demonstrated by studies using models of acute and controlled sleep deprivation, studies are needed to investigate the effects of chronic sleep deprivation as it occurs in the social jet lag. The aim of this study was to investigate the influence of social jet lag in circadian rest-activity markers and heart function in medical students. It is a cross-sectional, observational study conducted in the Laboratory of Neurobiology and Biological Rhythmicity (LNRB) at the Department of Physiology UFRN. Participated in the survey medical students enrolled in the 1st semester of their course at UFRN. Instruments for data collection: Munich Chronotype Questionnaire, Morningness Eveningness Questionnaire of Horne and ?stberg, Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, Actimeter; Heart rate monitor. Analysed were descriptive variables of sleep, nonparametric (IV60, IS60, L5 and M10) and cardiac indexes of time domain, frequency (LF, HF LF / HF) and nonlinear (SD1, SD2, SD1 / SD2). Descriptive, comparative and correlative statistical analysis was performed with SPSS software version 20. 41 students participated in the study, 48.8% (20) females and 51.2% (21) males, 19.63 ? 2.07 years. The social jet lag had an average of 02: 39h ? 00:55h, 82.9% (34) with social jet lag ? 1h and there was a negative correlation with the Munich chronotype score indicating greater sleep deprivation in subjects prone to eveningness. Poor sleep quality was detected in 90.2% (37) (X2 = 26.56, p <0.001) and 56.1% (23) excessive daytime sleepiness (X2 = 0.61, p = 0.435). Significant differences were observed in the values of LFnu, HFnu and LF / HF between the groups of social jet lag <2h and ? 2h and correlation of the social jet lag with LFnu (rs = 0.354, p = 0.023), HFnu (rs = - 0.354 , p = 0.023) and LF / HF (r = 0.355, p = 0.023). There was also a negative association between IV60 and indexes in the time domain and non-linear. It is suggested that chronic sleep deprivation may be associated with increased sympathetic activation promoting greater cardiovascular risk.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2016-07-06T20:38:09Z No. of bitstreams: 1 TiagoSiebertAltavini_TESE.pdf: 2131166 bytes, checksum: e6857312ffe2ac0d8a4cdc18238707e4 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2016-07-08T17:47:44Z (GMT) No. of bitstreams: 1 TiagoSiebertAltavini_TESE.pdf: 2131166 bytes, checksum: e6857312ffe2ac0d8a4cdc18238707e4 (MD5) / Made available in DSpace on 2016-07-08T17:47:44Z (GMT). No. of bitstreams: 1 TiagoSiebertAltavini_TESE.pdf: 2131166 bytes, checksum: e6857312ffe2ac0d8a4cdc18238707e4 (MD5) Previous issue date: 2016-01-29 / A atividade cerebral espont?nea exibe padr?es que lembram o de coativa??o de conjuntos neuronais em resposta a est?mulos ou tarefas. Estes padr?es tem sido atribu?dos a arquitetura funcional do c?rebro, e.g. conex?es de longo alcance em patches (manchas, fragmentos). N?s investigamos diretamente a contribui??o destas conex?es em patches entre hemisf?rios para mapas espont?neos e evocados na ?rea 18 pr?xima a borda 17/18 de gatos. Registramos mapas com imageamento por votage-sensitive dye (VSD) e atividade despiking enquanto manipulamos o input interhemisf?rico pela desativa??o revers?vel das ?reas correspondentes contralaterais. Durante a desativa??o os mapas espont?neos continuaram sendo gerados com frequ?ncia e qualidade semelhante ao da rede intacta, mas um vi?s de orienta??es cardinais desapareceu. Neur?nios com prefer?ncia por orienta??es horizontais (HN) ou verticais (VN), ao contr?rio dos de prefer?ncia obl?qua, diminuiram sua atividade de repouso, no entanto, HN tiveram a atividade diminu?da mesmo quando estimulados visualmente. Conclu?mos que mapas espont?neos estruturados s?o primariamente gerados por conex?es t?lamo- e/ou intracorticais. Entretanto, conex?es de longo alcance pelo corpo caloso - como um prolongamento da rede de longo alcance intracortical - contribui para um vi?s cardinal, possivelmente porque estas conex?es s?o mais fortes ou mais frequentes entre neur?nios preferindo orienta??es horizontais e/ou cardinais. Estes contornos s?o mais f?ceis de perceber e aparecem com mais frequ?ncia no ambiente natural, cone x?es de longo alcance podem prover o c?rtex visual com um grid de opera??es probabil?sticas de agrupamento em uma cena visual maior. / In the primary visual cortex, neurons with similar physiological features are clustered together in columns extending through all six cortical layers. These columns form modular orientation preference maps. Long-range lateral fibers are associated to the structure of orientation maps since they do not connect columns randomly; they rather cluster in regular intervals and interconnect predominantly columns of neurons responding to similar stimulus features. Single orientation preference maps ? the joint activation of domains preferring the same orientation - were observed to emerge spontaneously and it was speculated whether this structured ongoing activation could be caused by the underlying patchy lateral connectivity. Since long-range lateral connections share many features, i.e. clustering, orientation selectivity, with visual inter-hemispheric connections (VIC) through the corpus callosum we used the latter as a model for long-range lateral connectivity. In order to address the question of how the lateral connectivity contributes to spontaneously generated maps of one hemisphere we investigated how these maps react to the deactivation of VICs originating from the contralateral hemisphere. To this end, we performed experiments in eight adult cats. We recorded voltage-sensitive dye (VSD) imaging and electrophysiological spiking activity in one brain hemisphere while reversible deactivating the other hemisphere with a cooling technique. In order to compare ongoing activity with evoked activity patterns we first presented oriented gratings as visual stimuli. Gratings had 8 different orientations distributed equally between 0? and 180?. VSD imaged frames obtained during ongoing activity conditions were then compared to the averaged evoked single orientation maps in three different states: baseline, cooling and recovery. Kohonen self-organizing maps were also used as a means of analysis without prior assumption (like the averaged single condition maps) on ongoing activity. We also evaluated if cooling had a differential effect on evoked and ongoing spiking activity of single units. We found that deactivating VICs caused no spatial disruption on the structure of either evoked or ongoing activity maps. The frequency with which a cardinally preferring (0? or 90?) map would emerge, however, decreased significantly for ongoing but not for evoked activity. The same result was found by training self-organizing maps with recorded data as input. Spiking activity of cardinally preferring units also decreased significantly for ongoing when compared to evoked activity. Based on our results we came to the following conclusions: 1) VICs are not a determinant factor of ongoing map structure. Maps continued to be spontaneously generated with the same quality, probably by a combination of ongoing activity from local recurrent connections, thalamocortical loop and feedback connections. 2) VICs account for a cardinal bias in the temporal sequence of ongoing activity patterns, i.e. deactivating VIC decreases the probability of cardinal maps to emerge spontaneously. 3) Inter- and intrahemispheric long-range connections might serve as a grid preparing primary visual cortex for likely junctions in a larger visual environment encompassing the two hemifields.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2017-01-10T15:53:45Z No. of bitstreams: 1 AronDeMirandaHenriquesAlves_TESE.pdf: 2139619 bytes, checksum: 54285e7e9d5391a21bf97d42a9b9afaa (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2017-01-12T10:50:00Z (GMT) No. of bitstreams: 1 AronDeMirandaHenriquesAlves_TESE.pdf: 2139619 bytes, checksum: 54285e7e9d5391a21bf97d42a9b9afaa (MD5) / Made available in DSpace on 2017-01-12T10:50:01Z (GMT). No. of bitstreams: 1 AronDeMirandaHenriquesAlves_TESE.pdf: 2139619 bytes, checksum: 54285e7e9d5391a21bf97d42a9b9afaa (MD5) Previous issue date: 2015-12-16 / Os objetivos desta tese foram os de investigar padr?es comportamentais e eletrofisiol?gicos associados ? resili?ncia e suscetibilidade ao estresse social induzido em camundongos. Para isso, utilizamos um protocolo de indu??o de estresse cr?nico cont?nuo a partir de derrotas sociais baseado no paradigma residente-intruso. Os resultados da tese s?o apresentados em dois estudos. No primeiro estudo, camundongos C57BL/6J submetidos a epis?dios repetidos de derrota social apresentaram motiva??o tardia para interagir com um camundongo desconhecido em sess?es prolongadas (10 min) do teste de intera??o social. Utilizando uma abordagem etol?gica associada ? an?lise computacional de v?deos foi poss?vel rastrear precisamente a posi??o dos camundongos durante a realiza??o de comportamentos de investiga??o social. Analisamos ainda a express?o detalhada de comportamentos defensivos, tais como investiga??o em postura estendida e fugas, ambos associados ao comportamento de investiga??o social. A partir dessas an?lises demonstramos que a realiza??o do comportamento de investiga??o social em postura estendida era significativamente maior para o grupo derrotado comparado ao grupo controle. Ainda, um subgrupo de camundongos derrotados apresentou investiga??o social em postura estendida de forma persistente e sem habitua??o. Utilizando uma medida da dist?ncia de investiga??o durante as investiga??es sociais calculamos um ?ndice de aproxima??o (IA) para cada animal e separamos um subgrupo apresentando fen?tipo relacionado ? ansiedade. A incid?ncia de fugas tamb?m foi maior no grupo derrotado em compara??o com os controles. A persist?ncia na ocorr?ncia desse comportamento foi observada em um subgrupo de camundongos submetidos ?s derrotas sociais. Calculamos ent?o um ?ndice de fugas (IF) que se correlacionou inversamente com a prefer?ncia por sacarose, sendo ?til para identificar animais aned?nicos. No segundo estudo, foram combinados an?lise etol?gica e registros eletrofisiol?gicos com tetrodos na ?rea tegmentar ventral de camundongos submetidos ? derrotas sociais. Utilizando crit?rios eletrofisiol?gicos e farmacol?gicos classificamos unidades na ?rea tegmentar ventral como supostos neur?nios dopamin?rgicos e n?o-dopamin?rgicos. Durante o comportamento de investiga??o social foi observado que a modula??o da taxa de disparo dessas subpopula??es neuronais distintas ocorreu de maneira oposta em animais suscet?veis e resilientes ao estresse social. Em suma, propomos que sess?es prolongadas associadas ? an?lise etol?gica detalhada durante os testes de intera??o social podem prover informa??o para classifica??o de camundongos em resilientes e suscept?veis ap?s repetidas derrotas sociais. Ainda, a express?o do fen?tipo suscet?vel parece estar associada ao comprometimento do sistema dopamin?rgico mesol?mbico na atribui??o de valor de incentivo ?s intera??es sociais normalmente associadas ao aumento da atividade neuronal mesol?mbica. / The aims of this thesis were to investigate behavioral and electrophysiological patterns associated to resilience and susceptibility to social stress in mice. For this, we used a chronic social defeat stress protocol based on the resident-intruder paradigm. The results are presented here in two studies. In the first study, C57BL/6J mice submitted to repeated social defeat episodes showed delayed motivation to interact with an unfamiliar conspecific in long duration (10 min) sessions of the social interaction test. By using an ethological approach combined with computational video analysis, it was possible to track precisely the mouse position during social investigation behavior performance. With that approach, it was analyzed the detailed expression of defensive behaviors, such as stretched attended postures and flights, both associated to social investigation behaviors. From these analyzes, it was demonstrated that social investigation behaviors based on stretched attend postures were significantly higher in defeated mice in comparison to controls. Still, a subpopulation of defeated mice showed persistently and non-habituating stretched attend postures during social investigation. By using a measure based on the investigation distance during social investigations, it was possible to compute an approach index (AI) to each animal and separate a subpopulation showing an anxiety-related phenotype. The flight incidence was also increased in defeated group as compared with controls. The persistent occurrence of this behavior was observed in a subpopulation of defeated mice. We calculated a flight index (FI) that inversely correlated with sucrose preference, showing to be useful to identify anhedonic animals. In the second study, we combined ethological approach and electrophysiological recordings in the ventral tegmental area of mice submitted to chronic social defeat stress. By using electrophysiological and pharmacological criteria, single-units recorded from the ventral tegmental area were classified as putative dopaminergic and non-dopaminergic neurons. During the social investigation behavior it was observed that firing rate modulations of distinct neuronal subpopulations occurred in opposite manner in social defeat susceptible and resilient mice. In summary, this work proposes that longer sessions of the social interaction test associated to ethological approach can provide information for the behavioral classifications of resilient and susceptible mice after social defeat stress. Furthermore, the expression of susceptible phenotype could be related to the midbrain dopaminergic system impairment in the incentive value assignment to social interactions normally associated with increased mesolimbic neuronal activity.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2017-05-31T20:52:30Z No. of bitstreams: 1 BrunaSoaresLandeira_TESE.pdf: 8601965 bytes, checksum: a68be4513e6834f5aaf48800f8ea90d7 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2017-06-01T22:19:30Z (GMT) No. of bitstreams: 1 BrunaSoaresLandeira_TESE.pdf: 8601965 bytes, checksum: a68be4513e6834f5aaf48800f8ea90d7 (MD5) / Made available in DSpace on 2017-06-01T22:19:30Z (GMT). No. of bitstreams: 1 BrunaSoaresLandeira_TESE.pdf: 8601965 bytes, checksum: a68be4513e6834f5aaf48800f8ea90d7 (MD5) Previous issue date: 2017-04-11 / O c?rtex cerebral de mam?feros ? histologicamente organizado em diferentes camadas de neur?nios excitat?rios que possuem diversos padr?es de conex?o com alvos corticais e subcorticais. Durante o desenvolvimento, essas camadas corticais se estabelecem sequencialmente atrav?s de uma intrincada combina??o de especifica??o neuronal e migra??o em um padr?o radial conhecida como ?de dentro para fora?: neur?nios infragranulares s?o gerados primeiro do que os neur?nios granulares e supragranulares. Nas ?ltimas d?cadas, diversos genes codificando fatores de transcri??o envolvidos na especifica??o de neur?nios destinados a diferentes camadas corticais foram identificados. Todavia, a influ?ncia dos neur?nios infragranulares sobre a especifica??o das coortes neuronais subsequentes permanece pouco entendida. Para investigar os poss?veis efeitos da abla??o de neur?nios infragranulares sobre a especifica??o de neur?nios supragranulares, n?s induzimos a morte seletiva de neur?nios corticais das camadas V e VI antes da gera??o dos neur?nios destinados ?s camadas II-IV. Nossos dados revelam que um dia ap?s a abla??o, progenitores continuaram a gerar neur?nios destinados a camada VI que expressam o fator de transcri??o TBR1, enquanto praticamente nenhum neur?nio expressando TBR1 foi gerado na mesma etapa do desenvolvimento em controles com a mesma idade. Curiosamente, alguns neur?nios TBR1-positivos gerados ap?s a abla??o de neur?nios infragranulares se estabeleceram em camadas corticais superficiais, como esperado para neur?nios supragranulares gerados neste est?gio, sugerindo que a migra??o de neur?nios corticais pode ser controlada independentemente da sua especifica??o molecular. Al?m disso, n?s observamos um aumento em neur?nios de camada V que expressam CTIP2 e neur?nios calosos que expressam SATB2 ? custa da diminui??o neur?nios de camada IV em animais P0. Quando estes animais se tornam adultos jovens (P30) o aumento de neur?nios SATB2 e CTIP2 n?o existe mais, todavia encontramos esses neur?nios distribu?dos de forma diferente na ?rea somatossensorial dos animais que sofreram abla??o. Experimentos in vitro revelaram que a organiza??o citoarquitet?nica laminar do c?rtex ? necess?ria para gerar novamente os neur?nios TBR1+ que foram eliminados anteriormente. Al?m disso, experimentos in vitro indicam que em condi??o de baixa densidade celular os neur?nios tem seu fen?tipo alterado, expressando v?rios fatores de transcri??o ao mesmo tempo. Em conjunto, nossos dados indicam a exist?ncia de um mecanismo regulat?rio entre neur?nios infragranulares e progenitores envolvidos na gera??o de neur?nios supragranulares e/ou entre neur?nios infragranulares e neur?nios p?s-mit?ticos gerados em seguida. Este mecanismo poderia ajudar a controlar o n?mero de neur?nios em diferentes camadas e contribuir para o estabelecimento de diferentes ?reas corticais. / The cerebral cortex of mammals is histologically organized into in different layers of excitatory neurons that have distinct patterns of connections with cortical or subcortical targets. During development, these cortical layers are sequentially established through an intricate combination of neuronal specification and migration in a radial pattern known as "inside-out": deep-layer neurons are generated prior to upper-layer neurons. In the last few decades, several genes encoding transcription factors involved in the specification of neurons destined to different cortical layers have been identified. However, the influence of early-generated neurons in to the specification of subsequent neuronal cohorts remains unclear. To investigate the possible effects early born neurons ablation on the specification of late born neurons, we induced the selective death of cortical neurons from layers V and VI neurons before the generation of neurons destined to layers II, III and IV. Our data shows that oneday after ablation, progenitors resumed generation of layer VI neurons expressing the transcription factor TBR1, whereas virtually no TBR1-expressing neuron was generated at the same developmental stage in age-matched controls. Interestingly, many TBR1-positive neurons generated after deep-layer ablation settled within superficial cortical layers, as expected for upper-layer neurons generated at that stage, suggesting that migration post-mitotic neurons is independent of fate-specification. Furthermore, we observed an increase in layer V neurons expressing CTIP2 and cortico-cortical neurons expressing SATB2 at the expense of layer IV neurons in P0 animals. When these animals became young adults (P30) the increase os SATB2 and CTIP2 neurons is no longer observed, however these neurons are distributed in a different way in somatosensory areas from ablated animals. In vitro experiments show that the laminar cytoarchitectural organization of the cortex is necessary to regenerate the previously deleted TBR1 + neurons. In addition, in vitro experiments indicate that in a condition of low cell density the neurons phnotype is altered, they express several transcription factors at the same time. Together, our data indicate the existence of feedback mechanism either from early-generated neurons to progenitors involved in the generation of upper-layer neurons or from deep-layer neurons to postmitotic neurons generated subsequently. This mechanism could help to control the number of neurons in different layers and contribute to the establishment of different cortical areas.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2017-07-17T13:25:04Z No. of bitstreams: 1 RaphaelBenderChagasLeite_TESE.pdf: 4093723 bytes, checksum: 021488e56c69aed1d15a27179827dc0a (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2017-07-19T14:08:37Z (GMT) No. of bitstreams: 1 RaphaelBenderChagasLeite_TESE.pdf: 4093723 bytes, checksum: 021488e56c69aed1d15a27179827dc0a (MD5) / Made available in DSpace on 2017-07-19T14:08:37Z (GMT). No. of bitstreams: 1 RaphaelBenderChagasLeite_TESE.pdf: 4093723 bytes, checksum: 021488e56c69aed1d15a27179827dc0a (MD5) Previous issue date: 2017-02-23 / Nos seres humanos, o processamento da informa??o sonora possibilitou o aparecimento da linguagem oral e da m?sica. A altura sonora (do ingl?s, pitch), que permite a constru??o da melodia de uma m?sica e da pros?dia no discurso falado, ? um desses atributos. A percep??o da altura ? uma habilidade universal, contudo alguns indiv?duos se destacam por serem capazes de identificar ou produzir um tom em uma altura particular sem o uso de uma refer?ncia externa. Essa habilidade ? popularmente conhecida por ?Ouvido Absoluto? (em ingl?s, absolute pitch ou perfect pitch). No entanto, os mecanismos neurais respons?veis por tal habilidade ainda n?o s?o totalmente conhecidos. O presente trabalho tem o objetivo de contribuir para o entendimento dos processos neurais envolvidos na percep??o de alturas em indiv?duos com a habilidade de Ouvido Absoluto (OA). No nosso primeiro estudo, avaliamos a preval?ncia do OA em uma popula??o local de m?sicos (Escola de M?sica, UFRN). Para isso, utilizamos de ferramentas psicof?sicas e um question?rio. Nesse trabalho inicial, observamos que a habilidade do OA n?o se apresenta como um processo do tipo "tudo-ounada", mas sim com diferentes n?veis de desempenho: desde as pessoas que acertam abaixo do acaso, aumentando gradativamente a performance at? chegar aos 100%. Enquanto limiares tradicionais (~85%) mostraram uma preval?ncia de OA similar ?quela observada em m?sicos da Europa e Estados Unidos, a aplica??o de um limiar estat?stico resultou na detec??o de um n?mero maior de indiv?duos com algum grau de OA. Al?m disso, mostramos que indiv?duos com OA tem maior prefer?ncia de acerto para as chamadas notas naturais (aquelas relacionadas ?s teclas brancas no piano) em compara??o com as notas de teclas pretas (que s?o as notas sustenidas ou bem?is). Encontramos tamb?m que indiv?duos com OA apresentam in?cio mais precoce do treinamento musical. Finalmente, mostramos que quanto maior a profici?ncia musical, maior a preval?ncia dessa habilidade. Num segundo estudo, utilizamos potenciais evocados auditivos do tronco encef?lico (PEATE) para quantificar a ativa??o de n?cleos do tronco encef?lico no processamento de alturas de indiv?duos com OA. Nesse trabalho, mostramos a presen?a de respostas sustentadas (mas n?o transientes) com maior energia em indiv?duos com OA do que em m?sicos sem essa habilidade. Observamos tamb?m que a amplitude dessa resposta sustentada correlaciona-se com o tempo de rea??o em um teste de nomea??o de alturas. Esses resultados sugerem que indiv?duos com OA possuem maior refinamento no processamento da informa??o ac?stica nos primeiros est?gios do processamento auditivo, contribuindo assim para uma maior automatiza??o da identifica??o de alturas. Acreditamos que esses resultados, como um todo, poder?o facilitar entendimento das rela??es entre o desenvolvimento do sistema nervoso e o aprendizado musical, contribuindo assim para a elabora??o de novas t?cnicas de ensino de m?sica e programas de treinamento. / In humans, the processing of sound information allowed the appearance of speech and music. The pitch - which allows the melody of a song and prosody in spoken discourse - is one of these attributes. Pitch perception is a universal skill, however, just a few individuals are able to identify or produce a tone at a particular pitch without an external tonal reference, an ability known as the Absolute Pitch (AP). However, the neural mechanisms responsible for such ability are not yet fully understood. The present work has the objective to contribute to the understanding of the neural processes involved in the perception of pitch in AP possessors. In the first study, we evaluated AP prevalence in a local population of musicians (School of Music, UFRN). For this, we used psychophysical tools and a questionnaire. This first work showed that AP is not an "all-or-nothing" process, but rather that it has different levels of performance: from people that perform below chance, until it increases gradually to 100% of correct answers. While traditional thresholds (~85%) showed a prevalence of AP similar to that observed in musicians in Europe and the United States, the application of a statistical threshold resulted in the detection of a greater number of individuals with some degree of AP. In addition, we showed that AP possessors hit more the natural notes (those with the whitekeys of the piano) than those that are accidental (flat or sharp, i.e. the black keys of the piano). We also observed that AP possessors present an earlier onset of musical training. Finally, we showed that AP was more prevalent in a high proficiency group in comparison to the average proficiency group. In a second study, we used the auditory brainstem evoked potentials (ABR) to quantify the activation of brainstem nuclei in the processing of heights of individuals with OA. In this work, we showed that sustained responses (but not the transient ones) present a higher energy in individuals with AP than in control musicians. We also found that the amplitude of this sustained response correlates with the reaction time in a pitch naming test. These results suggest that individuals with AP have an increased refinement in the processing of acoustic information in the early stages of auditory processing, which would thus contribute to a greater automation of pitch identification. We believe that this thesis will contribute to the understanding of the relationship between nervous system development and musical learning, thus contributing to the development of new music teaching techniques and training programs.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2017-10-04T23:54:46Z No. of bitstreams: 1 BarbaraCiralliBoerner_DISSERT.pdf: 13754051 bytes, checksum: 1867ba4d0a14ecc5b81205405465f4fd (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2017-10-16T19:44:38Z (GMT) No. of bitstreams: 1 BarbaraCiralliBoerner_DISSERT.pdf: 13754051 bytes, checksum: 1867ba4d0a14ecc5b81205405465f4fd (MD5) / Made available in DSpace on 2017-10-16T19:44:38Z (GMT). No. of bitstreams: 1 BarbaraCiralliBoerner_DISSERT.pdf: 13754051 bytes, checksum: 1867ba4d0a14ecc5b81205405465f4fd (MD5) Previous issue date: 2017-08-18 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico (CNPq) / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES) / Vocaliza??es ultrass?nicas de ratos de freq??ncia fundamental na faixa de 30-90khz, conhecidas como usvs de '50 khz', est?o relacionadas a contextos apetitivos, como intera??es sociais, recompensa e acasalamento. No entanto, ainda n?o est? estabelecido como essas vocaliza??es contribuem para o comportamento social do rato. Dados anteriores do nosso grupo mostram que essas usvs est?o bem sincronizadas com a locomo??o do rato emissor, aumentando a possibilidade de que as vocaliza??es possam ajudar os ratos a se rastrearem no escuro. N?s testamos essa hip?tese ao avaliar como a desvocaliza??o de um ou dois ratos em pares de macho e f?mea afetaram suas intera??es espaciais durante o comportamento de acasalamento. As medidas de correla??o espacial, como dist?ncia m?dia entre os dois animais e n?mero e dura??o das persegui??es, foram analisadas para cada registro. Resultados preliminares sugerem que, embora a desvocaliza??o n?o influencie o sucesso do acasalamento, ela possa interferir especificamente nas r?pidas intera??es espaciais. / Rat ultrasonic vocalizations of fundamental frequency in the 30-90khz range known as '50 khz' usvs, are related to appetitive contexts such as social interactions, reward and mating. However, how these vocalizations contribute to rat social behaviour is not completely understood. Previous data from our lab shows that these usvs are tightly synchronized with the locomotion of the emitting rat, thus raising the possibility that vocalizations could help rats track each other in the dark. We here tested this hypothesis by assessing how devocalizing one or both rats in a male-female pair affected their spatial interactions during mating behavior. Metrics of spatial correlation, such as average distance between the two animals and number and duration of chases were analyzed for each record. Preliminary results suggest that, although devocalization does not influence success of mating, it may specifically interfere with fast spatial interactions.

Made available in DSpace on 2016-04-04T18:27:41Z (GMT). No. of bitstreams: 1 Marcelo Salomao Aros.pdf: 301474 bytes, checksum: fec723691e0499cfd0306cb8994ba743 (MD5) Previous issue date: 2008-02-17 / This study was aimed at evaluating scientific production about depression from 2004 to 2007 with a special focus on male depression and the tools used to assess this condition. By using the entries depression and scales, papers indexed within the Medline database were accessed. Approximately 6,400 abstracts were identified. Among these, 66 depression evaluation instruments were identified. For the study of the remaining variables, a decision was made to restrict the analyses to the production of 2007 due to the limited length of time for research. Among the 988 abstracts of 2007, 656 were regarded as appropriate for the aims of research and were then listed in chronological order. The following variables were analyzed: gender of the sample, country, age, language, type of instrument used for depression evaluation. Results point the Hamilton Depression Rating Scale (HDRS) as the most usual tool. The samples of research are mainly comprised by participants of both genders. Adulthood was the most usual age under study. The United States of America is the nation where most papers were published on the topic within that period of time. English is the most usual language of such publications. The nature of the instruments was mainly of self report type. Among the papers, 1.2% belonged to Brazilian authors and displayed the same profile presented by the global production. Only 3.7% of the papers were devoted to male depression. No tool was identified to measure male gender depression exclusively. Eight issues of interest were identified to study depression in male individuals and all of them referred to high stress situations: biological, social, and occupational. A considerable gap was perceived in the study of depression in male individuals with the most frequent profile found in hospital out-patient departments which assist the community. As a matter of conclusion, it was found that new instruments must be developed to evaluate depression, bringing features concerned with gender into focus, as the psychic demands and dynamics are particular and differentiated either for men or women. / A pesquisa teve como objetivo avaliar a produ??o cient?fica sobre depress?o no per?odo de 2004 a 2007, com especial ?nfase sobre a depress?o masculina e os instrumentos utilizados para avali?-la. Utilizando os verbetes, depress?o e escalas, foram acessados os artigos indexados na base de dados Medline. Foram identificados aproximadamente 6400 resumos. Neles, foram identificados 66 instrumentos de avalia??o de depress?o. Para o estudo das demais vari?veis, decidiu-se limitar as an?lises ? produ??o relativa ao ano de 2007, devido ?s limita??es de tempo. Dentre os 988 resumos do ano de 2007, 656 foram considerados adequados aos objetivos da investiga??o e foram listados pela sua ordem cronol?gica. Foram analisadas as seguintes vari?veis: g?nero da amostra estudada, pa?s, faixa et?ria, idioma, tipo de instrumento utilizado para a avalia??o da depress?o e a natureza dos instrumentos. Os resultados mostram que o instrumento mais utilizado ? a Hamilton Depression Rating Scale (HDRS). As amostras das pesquisas s?o prioritariamente compostas por participantes de ambos os g?neros. Os adultos foram a faixa et?ria mais estudada. Os Estados Unidos da Am?rica s?o a na??o que mais artigos publicou sobre o tema. O ingl?s ? o idioma mais utilizado. A natureza dos instrumentos para mensurar a depress?o foi prioritariamente de tipo self report. Dentre os artigos, 1,2% eram de autores brasileiros e conservavam o mesmo perfil da produ??o mundial. Apenas 3,7% dos artigos estudaram a depress?o no g?nero masculino. Nenhum instrumento foi identificado para mensurar exclusivamente a depress?o no g?nero masculino. Foram identificados oito temas de interesse para se estudar a depress?o no g?nero masculino e todos eles se referiam a situa??es de alto estresse: biol?gico, social e ocupacional. Verificou-se uma consider?vel lacuna no estudo da depress?o em indiv?duos masculinos com o perfil mais freq?entemente encontrado em ambulat?rios que assistem ? comunidade. Conclui-se que devem ser desenvolvidos novos instrumentos para a avalia??o da depress?o, em que caracter?sticas concernentes ao g?nero sejam valorizadas, pois as demandas e din?micas ps?quicas s?o particulares e diferenciadas para homens e mulheres.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2016-02-23T00:01:15Z No. of bitstreams: 1 JessicaAlvesDeMedeirosAraujo_DISSERT.pdf: 20630647 bytes, checksum: 1016136129718286256c9eeb291a89c5 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2016-02-26T22:00:54Z (GMT) No. of bitstreams: 1 JessicaAlvesDeMedeirosAraujo_DISSERT.pdf: 20630647 bytes, checksum: 1016136129718286256c9eeb291a89c5 (MD5) / Made available in DSpace on 2016-02-26T22:00:54Z (GMT). No. of bitstreams: 1 JessicaAlvesDeMedeirosAraujo_DISSERT.pdf: 20630647 bytes, checksum: 1016136129718286256c9eeb291a89c5 (MD5) Previous issue date: 2015-04-08 / A possibilidade de repor c?lulas perdidas em doen?as neurodegenerativas atrav?s de transplantes com c?lulas-troncos das mais diversas fontes vem sendo amplamente estudada. As c?lulas-tronco adultas (CTA) podem ser facilmente isoladas e sua utiliza??o na pesquisa n?o envolve quest?es ?ticas e religiosas. Al?m disso, estas c?lulas s?o menos prop?cias ? transforma??o tumoral do que c?lulas-tronco embrion?rias, outra importante fonte de c?lulas para terapias celulares. No entanto, as CTA s?o, em estados fisiol?gicos, restritas a gera??o de c?lulas dos seus tecidos de origem, o que poderia limitar a sua utiliza??o. Por?m, nos ?ltimos anos, uma s?rie de t?cnicas vem sendo descritas com o objetivo de reverter tais limita??es. Neste trabalho, n?s investigamos a capacidade das c?lulas-tronco mesenquimais adultas, isoladas de camundongos ou do cord?o umbilical humano, serem induzidas a adquirir um fen?tipo neuronal de forma direta, sem passar por um est?gio de c?lula progenitora ou pluripotente, atrav?s da reprograma??o gen?tica com genes pr?-neurais. Nossos resultados indicam que tanto c?lulas-tronco mesenquimais adultas murinas quanto humanas podem ser reprogramadas em neur?nios ap?s a express?o combinada de Sox2 e Ascl1 ou Sox2 e Neurog2. As c?lulas reprogramadas exibem morfologias compat?veis com o fen?tipo neuronal, expressam prote?nas t?picas de neur?nios maduros, apresentam a capacidade de gerar potenciais de a??o repetitivos e formam conex?es sin?pticas com outros neur?nios presentes no cultivo. Portanto, nosso trabalho apresenta a primeira evid?ncia de reprograma??o direta de c?lulas-tronco mesenquimais humanas em neur?nios funcionais.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2016-03-10T21:38:11Z No. of bitstreams: 1 BryanDaCostaSouza_DISSERT.pdf: 4719044 bytes, checksum: 0f6079a62146ca8bda3028f6b52ae503 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2016-03-17T22:42:15Z (GMT) No. of bitstreams: 1 BryanDaCostaSouza_DISSERT.pdf: 4719044 bytes, checksum: 0f6079a62146ca8bda3028f6b52ae503 (MD5) / Made available in DSpace on 2016-03-17T22:42:15Z (GMT). No. of bitstreams: 1 BryanDaCostaSouza_DISSERT.pdf: 4719044 bytes, checksum: 0f6079a62146ca8bda3028f6b52ae503 (MD5) Previous issue date: 2015-03-13 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / As principais vias aferentes ao hipocampo v?m do c?rtex entorrinal e fazem parte de um loop que retorna ao entorrinal ap?s passar pelo giro denteado, e pelas subareas do hipocampo CA3 e CA1. Desde a descoberta nos anos 50 de que o hipocampo est? envolvido na forma??o de mem?rias, esta regi?o vem sendo extensivamente estudada. Al?m desta fun??o mnem?nica, o hipocampo tamb?m est? associado a navega??o espacial. Em camundongos e ratos, c?lulas de lugar exibem um aumento da taxa de disparo relacionado ? posi??o do animal. O local do ambiente onde uma determinada c?lula de lugar se ativa ? chamado de campo de lugar. A taxa de disparo das c?lulas de lugar ? m?xima quando o animal est? no centro do campo de lugar, e diminui a medida que ele se afasta desse ponto, sugerindo a exist?ncia de uma codifica??o espacial baseada em taxa de disparos. Entretanto, pesquisas pr?vias v?m mostrando a exist?ncia de oscila??es hipocampais em m?ltiplas frequ?ncias e ligadas a diferentes estados comportamentais, e muitos acreditam que estas oscila??es s?o importantes para uma codifica??o temporal. Em particular, oscila??es teta (5-12 Hz) possuem uma rela??o espa?o-temporal com as c?lulas de lugar conhecida como precess?o de fase. Na precess?o, a fase de disparos da c?lula de lugar muda gradualmente do pico de teta para o fundo e, posteriormente, para a fase ascendente, a medida que o animal atravessa o campo de lugar. Al?m disso, as teorias vigentes sugerem que CA1, a porta de sa?da do hipocampo, intermediaria a comunica??o com o c?rtex entorrinal e CA3 atrav?s de oscila??es em diferentes frequ?ncias chamadas, respectivamente, de gama alto (60-100 Hz; HG) e gama baixo (30-60 Hz; LG). Essas oscila??es se relacionam com teta, estando aninhadas dentro de cada ciclo desta frequ?ncia mais lenta. Nesta disserta??o, utilizamos dados disponibilizados online para fazer an?lises computacionais visando reproduzir resultados cl?ssicos e recentes acerca da atividade das c?lulas de lugar no hipocampo de ratos em livre movimento. Em particular, n?s revisitamos o debate sobre a rela??o da precess?o de fase com varia??es na taxa de disparos e na posi??o do animal no campo de lugar. Conclu?mos que este fen?meno n?o pode ser explicado por nenhuma dessas vari?veis sozinha, e sim pela intera??o entre elas. N?s tamb?m realizamos novas an?lises investigando as propriedades das c?lulas de lugar em rela??o ?s oscila??es. N?s mostramos que o n?vel de modula??o dos disparos por teta afeta apenas levemente a informa??o espacial contida nas c?lulas de lugar, enquanto a fase de disparo m?dia n?o tem nenhuma influ?ncia na informa??o espacial. Tamb?m encontramos que as c?lulas de lugar est?o moduladas por teta quando disparam fora do campo de lugar. Al?m disso, nossos resultados mostram que o disparo das c?lulas de lugar dentro do ciclo de teta segue os padr?es de modula??o de HG e LG por teta presentes nos potenciais de campo local de CA1 e c?rtex entorrinal. Por ?ltimo, achamos um acoplamento fase-amplitude em CA1 associado apenas aos disparos dentro do campo de lugar na faixa de 40-80 Hz. Conclu?mos que o disparo de c?lulas de lugar est? ligado a estados de rede refletidos no potencial de campo local e sugerimos que a atividade dessas c?lulas sejam interpretadas como um estado din?mico ao inv?s de uma propriedade fixa da c?lula. / The main inputs to the hippocampus arise from the entorhinal cortex (EC) and form a loop involving the dentate gyrus, CA3 and CA1 hippocampal subfields and then back to EC. Since the discovery that the hippocampus is involved in memory formation in the 50's, this region and its circuitry have been extensively studied. Beyond memory, the hippocampus has also been found to play an important role in spatial navigation. In rats and mice, place cells show a close relation between firing rate and the animal position in a restricted area of the environment, the so-called place field. The firing of place cells peaks at the center of the place field and decreases when the animal moves away from it, suggesting the existence of a rate code for space. Nevertheless, many have described the emergence of hippocampal network oscillations of multiple frequencies depending on behavioral state, which are believed to be important for temporal coding. In particular, theta oscillations (5-12 Hz) exhibit a spatio-temporal relation with place cells known as phase precession, in which place cells consistently change the theta phase of spiking as the animal traverses the place field. Moreover, current theories state that CA1, the main output stream of the hippocampus, would interplay inputs from EC and CA3 through network oscillations of different frequencies, namely high gamma (60-100 Hz; HG) and low gamma (30-50 Hz; LG), respectively, which tend to be nested in different phases of the theta cycle. In the present dissertation we use a freely available online dataset to make extensive computational analyses aimed at reproducing classical and recent results about the activity of place cells in the hippocampus of freely moving rats. In particular, we revisit the debate of whether phase precession is due to changes in firing frequency or space alone, and conclude that the phenomenon cannot be explained by either factor independently but by their joint influence. We also perform novel analyses investigating further characteristics of place cells in relation to network oscillations. We show that the strength of theta modulation of spikes only marginally affects the spatial information content of place cells, while the mean spiking theta phase has no influence on spatial information. Further analyses reveal that place cells are also modulated by theta when they fire outside the place field. Moreover, we find that the firing of place cells within the theta cycle is modulated by HG and LG amplitude in both CA1 and EC, matching cross-frequency coupling results found at the local field potential level. Additionally, the phase-amplitude coupling in CA1 associated with spikes inside the place field is characterized by amplitude modulation in the 40-80 Hz range. We conclude that place cell firing is embedded in large network states reflected in local field potential oscillations and suggest that their activity might be seen as a dynamic state rather than a fixed property of the cell.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2017-10-04T23:54:46Z No. of bitstreams: 1 CarolinaAraujoSousa_DISSERT.pdf: 4069494 bytes, checksum: 9b768a46fbe08e2407ed147faed6bc74 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2017-10-16T20:38:12Z (GMT) No. of bitstreams: 1 CarolinaAraujoSousa_DISSERT.pdf: 4069494 bytes, checksum: 9b768a46fbe08e2407ed147faed6bc74 (MD5) / Made available in DSpace on 2017-10-16T20:38:12Z (GMT). No. of bitstreams: 1 CarolinaAraujoSousa_DISSERT.pdf: 4069494 bytes, checksum: 9b768a46fbe08e2407ed147faed6bc74 (MD5) Previous issue date: 2017-08-31 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico (CNPq) / A forma??o de circuitos neurais durante o desenvolvimento se d? atrav?s de uma complexa intera??o entre fatores gen?ticos e ambientais, que influenciam m?ltiplos eventos como a neurog?nese, a sinaptog?nese e a mieliniza??o. Em transtornos do desenvolvimento, como o transtorno do espectro autista (TEA), intercorr?ncias nesse processo levam ? m?-forma??o da circuitaria neural e, consequentemente, a d?ficits de intera??o social, interesses restritos e movimentos estereotipados, entre outros. Recentemente, realizamos em nosso laborat?rio a an?lise do transcriptoma do c?rtex frontal no modelo animal de autismo induzido por exposi??o a ?cido valpr?ico (VPA) in utero. Observamos que ratos com 15 dias de idade (P15) apresentam aumento da express?o de genes relacionados ? estabilidade sin?ptica e redu??o de genes relacionado ? mielina, sugerindo poss?veis mecanismos moleculares para as varia??es comportamentais previamente observadas nestes animais. Portanto, o objetivo desta disserta??o foi aprofundar este estudo investigando o padr?o de mieliniza??o no enc?falo de animais tratados com VPA em diferentes idades p?s-natais (infantil: P15 e adulta: P60). Para tanto, os grupos experimental e controle foram gerados, respectivamente, atrav?s da inje??o de VPA (500 mg/kg i.p.) ou salina em f?meas gr?vidas durante o dia embrion?rio 12.5 (E12.5). A an?lise da integridade da mielina foi realizada por duas abordagens: (1) an?lise da express?o de genes relacionados ? mielina (Mobp, Plp1, Mag e Klhl1), por PCR quantitativo, no c?rtex frontal de animais em P15; e (2) quantifica??o histol?gica da distribui??o de mielina em cinco sub-regi?es do c?rtex frontal e corpo caloso de animais P15 e P60. Dos quatro genes avaliados, observamos significativa diminui??o na express?o de Mobp e Mag em animais VPA em P15. A an?lise histol?gica de mielina mostrou redu??o significativa na intensidade de marca??o no c?rtex cingulado anterior em animais VPA em P60, por?m n?o detectou diferen?a na intensidade de marca??o em animais VPA em P15 quando comparados aos controles. Conclu?mos assim que animais VPA neonatos t?m reduzida express?o de genes relacionados a compacta??o da mielina, por?m sem altera??es no conte?do lip?dico da mielina nas ?reas analisadas. Animais adultos, por sua vez, apresentaram altera??es no conte?do lip?dico da mielina no c?rtex cingulado anterior. Em conjunto, estes resultados sugerem que dist?rbios na comunica??o entre circuitos frontais neste modelo de autismo podem ocorrer inicialmente devido altera??es na organiza??o da mielina, levando a redu??es de mielina no adulto. / The formation of brain circuits during neural development occurs through the interaction between timely regulated genetic and environmental signals, which influence multiple events such as neurogenesis, synaptogenesis, and myelination. In developmental disorders, such as autism spectrum disorders (ASD), deficits in these processes may lead to neural circuitry malformations and, in consequence, to social interaction deficits, restricted interests, and stereotyped movements, among others. Recently, we performed a transcriptome analysis of the frontal cortex of an animal model of autism induced by valproic acid (VPA) in utero in our lab. We observed that VPA animals at the postnatal age 15 (P15) show an increased expression of genes related to synaptic stability and a decrease in the expression of myelin-related genes, suggesting possible molecular mechanisms for the behavioral deficits previously observed in these animals. Therefore, the aim of this Master?s thesis was to further investigate the myelination pattern in the forebrain of VPA-treated rats at different postnatal ages (infant: P15 and adult: P60). For that, experimental and control groups were generated by injecting pregnant dams with 500 mg/Kg i.p. VPA or saline, respectively, on embryonic day 12.5 (E12.5). Analysis of myelin integrity was conducted by two different approaches: (1) gene expression analysis of myelin-related genes (Mobp, Plp1, Mag, and Klhl1) in dissected samples of the frontal cortex of P15 rats by quantitative real-time PCR; and (2) histological quantification of myelin distribution in five sub-regions of the frontal cortex and corpus callosum of P15 and P60 animals. Of all genes analyzed, we observed a significant decrease in Mobp and Mag expression in P15 VPA animals. Myelin analysis showed a significant reduction in myelin staining in the anterior cingulate cortex of VPA animals at P60, but no differences were observed at P15. In conclusion, infant VPA rats showed reduced expression of genes related to myelin assembly, without alterations in the lipid content of myelin in the areas analyzed. Adult animals, in contrast, showed a decrease in lipid content of myelin in the anterior cingulate cortex. Together, these results suggest that communication abnormalities in frontal circuits in this animal model of autism may occur initially due to alterations in myelin organization, leading to myelin reduction in adulthood.