Made available in DSpace on 2015-04-14T14:51:16Z (GMT). No. of bitstreams: 1 437812.pdf: 154195 bytes, checksum: 6d937534253a5ebf131f023920cdd572 (MD5) Previous issue date: 2011-11-11 / Background: Age related reductions in contextual memory can impair daily functioning of older adults and have an important impact on their quality of life. Thus, the understanding of the neurobiological correlates of this memory decline is important to the establishment of effective cognitive interventions in healthy older adults. Objective: The current study was aimed to investigate the effects of aging and prefrontal cortex (PFC) function on contextual memory performance under different encoding conditions in a naturalistic experimental paradigm. Methods: Young (n=34, aged 20 - 35 years) and older adult men (n=31; aged 54 - 87 years) matched for education completed a recognition memory task for context (location of objects depicted in different rooms of a house) with or without an incidental binding cue at encoding. In addition, Wisconsin Card Sorting Test (WCST) was carried out to assess PFC function. Results: Results for contextual memory performance showed significant main effects of aging and encoding condition. Older adults performed significantly poorer than young controls in the encoding condition without incidental binding cue. The introduction of the incidental binding cue at encoding significantly improved the context recognition scores in young and older adults. A significant association between WCST scores and the performance for contextual memory were found only in the task without binding cue and just for the older adult men. Conclusion: The main findings indicate that the age related deficits on contextual memory are associated to age related impairments of PFC function, as indicated by the WCST. However, contextual memory of older adults improved with cognitive support at encoding and became independent of the scores on WCST, suggesting that incidental associative binding instructions at encoding can mitigate PFC deficits. / Introdu??o: Redu??es na mem?ria contextual relacionadas ? idade podem prejudicar o funcionamento di?rio dos idosos e t?m um impacto importante na sua qualidade de vida. Assim, a compreens?o dos correlatos neurobiol?gicos deste decl?nio da mem?ria ? importante para o estabelecimento de interven??es cognitivas eficazes em idosos saud?veis. Objetivo: O presente estudo teve como objetivo investigar os efeitos do envelhecimento e da fun??o do c?rtex pr?-frontal (CPF) sobre o desempenho da mem?ria contextual em condi??es diferentes de codifica??o em um paradigma experimental naturalista. M?todos: Jovens (n = 34; 26,02 ? 0,64) e idosos (n = 31; 69,09 ? 1,26) do sexo masculino pareados por n?vel educacional. Os volunt?rios foram submetidos a uma tarefa de mem?ria de reconhecimento de contexto (localiza??o de objetos representados em diferentes salas de uma casa) com ou sem uma estrat?gia de codifica??o associativa. Al?m disso, o Teste Wisconsin de Classifica??o de Cartas (WCST) foi realizado para avaliar a integridade funcional do CPF. Resultados: Os resultados para o desempenho da mem?ria contextual mostrou efeitos significativos do envelhecimento e da estrat?gia de codifica??o. Os idosos tiveram um desempenho significativamente pior do que controles jovens na condi??o de codifica??o sem estrat?gia de codifica??o. A introdu??o da estrat?gia de codifica??o melhorou significativamente as pontua??es do reconhecimento do contexto nos jovens e idosos. A associa??o significativa entre as pontua??es WCST e o desempenho da mem?ria contextual foram encontrados apenas nos idosos sem estrat?gia de codifica??o. Conclus?o: As principais conclus?es indicam que os d?ficits na mem?ria contextual e dist?rbios da fun??o do CPF est?o relacionados com a idade, como indicado pelo WCST. No entanto, a mem?ria contextual dos idosos melhorou, com o a introdu??o da estrat?gia de codifica??o associativa e tornou-se independente da pontua??o no WCST, sugerindo a estrat?gia de codifica??o associativa pode atenuar os d?ficits do CPF.

Submitted by PPG Medicina e Ci?ncias da Sa?de (medicina-pg@pucrs.br) on 2017-12-26T13:48:34Z No. of bitstreams: 1 CAROLINA_GARRIDO_ZINN_TES.pdf: 7131704 bytes, checksum: 554f552cadd232d7ef553c1f275476ba (MD5) / Approved for entry into archive by Caroline Xavier (caroline.xavier@pucrs.br) on 2017-12-29T11:25:22Z (GMT) No. of bitstreams: 1 CAROLINA_GARRIDO_ZINN_TES.pdf: 7131704 bytes, checksum: 554f552cadd232d7ef553c1f275476ba (MD5) / Made available in DSpace on 2017-12-29T11:48:08Z (GMT). No. of bitstreams: 1 CAROLINA_GARRIDO_ZINN_TES.pdf: 7131704 bytes, checksum: 554f552cadd232d7ef553c1f275476ba (MD5) Previous issue date: 2017-08-31 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / The social recognition memory (SRM) is crucial to reproduction, formation of social groups and species survival. It is well known that oxytocin, vasopressin, sexual hormones and the olfactory bulb are strongly involved in the formation of SEM. Despite its relevance, the involvement of neurotransmitters such as dopamine (DA), noradrenaline (NE) and histamine (HIS), as well as the brain structures basolateral amygdala (BLA) and CA1 region of dorsal hippocampus ? commonly known for their importance in consolidating and maintaining other types of memories ? remains unknown when concerning SRM. Therefore, the first part of this study aims to evaluate the participation of the D1/D5 dopaminergic, ?-adrenergic and H2 histaminergic receptors into BLA and CA1 on consolidation of SRM. For this, male Wistar adult rats (3 months) were submitted to the social discrimination task (SDT), which is based on the natural tendency of the rodents to explore the novelty. The adult animal was exposed to a juvenile (21 days) conspecific for 1 hour (training session) and 24 hours later to the juvenile previously met (familiar) and to a new juvenile during 5 minutes (test session), when the exploration time was measured. Pharmacological interventions took place immediately after the training session. We verified that the H2 histaminergic receptors are required to the consolidation of SRM both in CA1 and BLA. However, the activation of D1/D5 dopaminergic and ?-adrenergic receptors interferes in an opposite way in the two brain structures: D1/D5 receptors are required in CA1, but not in BLA for consolidation of MRS, whereas activation of ?-adrenergic receptors is indispensable in BLA, but not in CA1. Methylphenidate (MPH) is a drug widely used in the treatment of Attention Deficit Hyperactivity Disorder. It exerts its therapeutic effect by increasing levels of DA and NE in brain structures involved in the learning processes, such as prefrontal cortex (PFC) and hippocampus. Since DA and NE have opposite actions in MRS, we decided to evaluate the effect of MPH on the formation and recall of MRS, since this drug acts on the levels of both neurotransmitters and has been used for academic doping by healthy individuals. Using SDT, with pharmacological interventions at different times, we verified that: 1) MPH, administered acutely prior to the information acquisition, blocked SRM; 2) Blockade was reversed when the animals received MPH at the time of acquisition and retrieval, characterizing the phenomenon known as state dependency (SD) learning; 3) The SD is associated to the CPF, but not to CA1; 4) SD does not depend on CA1, since the increase of NE in CA1 impairs the retrieval of the SRM. In addition, we verified that the 21-day chronic treatment with MPH causes a greater persistence of MRS when a weaker training session is performed. Considering the obtained results, this work demonstrates that the hippocampus, the basolateral amygdala and the prefrontal cortex, modulated by the dopaminergic and noradrenergic systems, regulate the SRM processing. / A mem?ria de reconhecimento social (MRS) ? crucial ? reprodu??o, forma??o de grupos sociais e sobreviv?ncia das esp?cies. Sabe-se que a ocitocina, a vasopressina, os horm?nios sexuais e o bulbo olfat?rio t?m um forte envolvimento na forma??o da MRS. Apesar de sua relev?ncia, a participa??o de neurotransmissores, como dopamina (DA), noradrenalina (NA) e histamina (HIS), bem como das estruturas am?gdala basolateral (BLA) e regi?o CA1 do hipocampo (CA1) ? j? amplamente conhecidos pela sua import?ncia na consolida??o e manuten??o de outros tipos de mem?rias ? permanece desconhecido quanto ? MRS. Sendo assim, a primeira parte deste trabalho buscou avaliar a participa??o dos receptores D1/D5 dopamin?rgicos, ?-adren?rgicos e H2 histamin?rgicos na BLA e CA1 sobre a consolida??o da MRS. Para isso, ratos Wistar machos adultos (3 meses) foram submetidos a tarefa de discrimina??o social (TDS), que baseia-se na tend?ncia natural dos roedores de explorar a novidade. O animal adulto foi exposto a um juvenil (21 dias) coespec?fico por 1 hora (sess?o de treino) e 24 horas depois ao juvenil previamente encontrado (familiar) e a um novo juvenil durante 5 minutos (sess?o de teste), quando o tempo de explora??o foi medido. As interven??es farmacol?gicas ocorreram imediatamente ap?s a sess?o de treino. Verificou-se que os receptores H2 histamin?rgicos s?o necess?rios para a consolida??o da mem?ria tanto em CA1 quanto na BLA. Contudo a ativa??o dos receptores D1/D5 dopamin?rgicos e ?-adren?rgicos interfere de forma oposta nas duas estruturas cerebrais: os receptores D1/D5 s?o necess?rios em CA1, mas n?o na BLA para a consolida??o da MRS, enquanto a ativa??o dos receptores ?adren?rgicos ? indispens?vel na BLA, por?m n?o em CA1. O metilfenidato (MPH) ? um f?rmaco amplamente utilizado no tratamento do Transtorno do D?ficit de Aten??o e Hiperatividade. Exerce seu efeito terap?utico pelo aumento nos n?veis de DA e NA em estruturas cerebrais envolvidas nos processos de aprendizagem, como c?rtex pr?frontal (CPF) e hipocampo. Uma vez que a DA e a NA tem a??es opostas na MRS, decidimos avaliar o efeito do MPH sobre a forma??o e a evoca??o da MRS, j? que esta droga atua sobre os n?veis de ambos os neurotransmissores e tem sido utilizada como doping acad?mico por indiv?duos saud?veis. Utilizando a TDS, com as interven??es farmacol?gicas em diferentes momentos, verificamos que: 1) o MPH, administrado de forma sist?mica aguda previamente ? aquisi??o da informa??o, bloqueou a MRS; 2) O bloqueio foi revertido quando os animais receberam MPH no momento da aquisi??o e da evoca??o, caracterizando o fen?meno conhecido como depend?ncia de estado (DE); 3) A DE ? associada ao CPF, mas n?o a CA1; 4) A DE n?o depende de CA1, pois o aumento de NA em CA1 prejudica a evoca??o da MRS. Al?m disso, verificamos que o tratamento cr?nico de 21 dias com MPH causa uma maior persist?ncia da MRS, quando realizada uma sess?o de treino mais fraca. Considerando os resultados obtidos, este trabalho demonstra que o hipocampo, a am?gdala basolateral e o c?rtex pr?-frontal, modulados pelos sistemas dopamin?rgico e noradren?rgico, regulam o processamento da MRS.

Made available in DSpace on 2014-12-17T15:28:53Z (GMT). No. of bitstreams: 1 JulianaABMS_DISSERT.pdf: 2223845 bytes, checksum: 223f33020eca4ef9f2713bc27ef300ca (MD5) Previous issue date: 2013-08-23 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / Autism comprises a heterogeneous group of neurodevelopmental disorders that affects the brain maturation and produces sensorial, motor, language and social interaction deficits in early childhood. Several studies have shown a major involvement of genetic factors leading to a predisposition to autism, which are possibly affected by environmental modulators during embryonic and post-natal life. Recent studies in animal models indicate that alterations in epigenetic control during development can generate neuronal maturation disturbances and produce a hyper-excitable circuit, resulting in typical symptoms of autism. In the animal model of autism induced by valproic acid (VPA) during rat pregnancy, behavioral, electrophysiological and cellular alterations have been reported which can also be observed in patients with autism. However, only a few studies have correlated behavioral alterations with the supposed neuronal hyper-excitability in this model. The aim of this project was to generate an animal model of autism by pre-natal exposure to VPA and evaluate the early post-natal development and pre-puberal (PND30) behavior in the offspring. Furthermore, we quantified the parvalbumin-positive neuronal distribution in the medial prefrontal cortex and Purkinje cells in the cerebellum of VPA animals. Our results show that VPA treatment induced developmental alterations, which were observed in behavioral changes as compared to vehicle-treated controls. VPA animals showed clear behavioral abnormalities such as hyperlocomotion, prolonged stereotipies and reduced social interaction with an unfamiliar mate. Cellular quantification revealed a decrease in the number of parvalbumin-positive interneurons in the anterior cingulate cortex and in the prelimbic cortex of the mPFC, suggesting an excitatory/inhibitory unbalance in this animal model of autism. Moreover, we also observed that the neuronal reduction occurred mainly in the cortical layers II/III and V/VI. We did not detect any change in the density of Purkinje neurons in the Crus I region of the cerebellar cortex. Together, our results strengthens the face validity of the VPA model in rats and shed light on specific changes in the inhibitory circuitry of the prefrontal cortex in this autism model. Further studies should address the challenges to clarify particular electrophysiological correlates of the cellular alterations in order to better understand the behavioral dysfunctions / O autismo compreende um grupo heterog?neo de desordens do neurodesenvolvimento que afetam a matura??o cerebral e produzem d?ficits sensoriais, motores, de linguagem e de intera??o social no in?cio da inf?ncia. Diversos estudos tem demonstrado um importante envolvimento de fatores gen?ticos que levam ? predisposi??o ao autismo, que s?o possivelmente afetados por modula??es ambientais durante a vida embrion?ria e p?s-natal. Estudos recentes em modelos animais indicam que altera??es no controle epigen?tico durante o desenvolvimento podem gerar dist?rbios na matura??o neuronal e produzir um circuito hiper-excit?vel, resultando em sintomas t?picos do autismo. No modelo animal de autismo induzido por ?cido valpr?ico (VPA) durante a gesta??o de ratas, foram observadas altera??es comportamentais, eletrofisiol?gicas e celulares semelhantes ?s observadas nos pacientes com autismo. Entretanto, ainda s?o poucos os estudos que correlacionam altera??es comportamentais com a suposta hiper-excitabilidade neuronal desse modelo. O objetivo desse estudo foi de gerar o modelo animal de autismo por exposi??o pr?-natal ao VPA e avaliar o desenvolvimento e comportamento p?s-natal e pr?-p?bere (PND 30). Al?m disso, quantificamos a distribui??o neuronal de interneur?nios parvalbumina-positivos no c?rtex pr?-frontal medial (CPFm) e de c?lulas de Purkinje no cerebelo de animais VPA. Nossos resultados mostraram que o tratamento com VPA induziu altera??es no desenvolvimento, que foram observadas em altera??es comportamentais quando comparadas com os animais controle. Animais VPA mostraram claras altera??es comportamentais, como hiperlocomo??o, estereotipia prolongada e redu??o na intera??o social com animal n?o-familiar. A quantifica??o celular revelou uma diminui??o no n?mero de interneur?nios parvalbumina-positivos no c?rtex cingulado anterior e no c?rtex pr?-l?mbico, sugerindo um desbalan?o na excita??o/inibi??o nesse modelo animal de autismo. Tamb?m observamos que essa redu??o ocorreu principalmente nas camadas corticais II/III e V/VI. N?o observamos modifica??o na densidade de c?lulas de Purkinje na regi?o Crus I do c?rtex cerebelar. Em conjunto, nossos resultados fortalecem a validade de face do modelo VPA em ratos e relatam modifica??es espec?ficas na circuitaria inibit?ria do CPFm nesse modelo de autismo. Novos estudos devem abordar correlatos eletrofisiol?gicos particulares com altera??es celulares, de forma a esclarecer as disfun??es comportamentais encontradas nesse modelo animal

Made available in DSpace on 2014-12-17T15:36:38Z (GMT). No. of bitstreams: 1 JoanilsonGS_TESE.pdf: 3996700 bytes, checksum: 8b3084030c1c254db2c08a440881ea9a (MD5) Previous issue date: 2011-05-02 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico / Cortical interneurons are characterized by their distinct morphological, physiological and biochemical properties, acting as modulators of the excitatory activity by pyramidal neurons, for example. Various studies have revealed differences in both distribution and density of this cell group throughout distinct cortical areas in several species. A particular class of interneuron closely related to cortical modulation is revealed by the immunohistochemistry for calcium binding proteins calbindin (CB), calretinina (CR) and parvalbumin (PV). Despite the growing amount of studies focusing on calcium binding proteins, the prefrontal cortex of primates remains relatively little explored, particularly in what concerns a better understanding of the organization of the inhibitory circuitry across its subdivisions. In the present study we characterized the morphology and distribution of neurons rich in calcium-binding proteins in the medial, orbital and dorsolateral areas of the prefrontal cortex of the marmoset (Callithrix jacchus). Using both morphometric and stereological techniques, we found that CR-reactive neurons (mainly double bouquet and bipolar cells) have a more complex dendritic arborization than CB-reactive (bitufted and basket cells) and PV-reactive neurons (chandelier cells). The neuronal densities of CR- and CB-reactive cells are higher in the supragranular layers (II/III) whilst PV-reactive neurons, conversely, are more concentrated in the infragranular layers (V/VI). CR-reactive neurons were the predominant group in the three regions evaluated, being most prevalent in dorsomedial region. Our findings point out to fundamental differences in the inhibitory circuitry of the different areas of the prefrontal cortex in marmoset / Os interneur?nios do c?rtex cerebral s?o caracterizados por suas diferentes propriedades morfol?gicas, fisiol?gicas e bioqu?micas, atuando como moduladores da atividade excitat?ria cortical dos neur?nios piramidais, por exemplo. V?rios estudos revelaram diferen?as na distribui??o e densidade deste grupo celular ao longo de diferentes ?reas corticais em diversas esp?cies. Uma classe particular de interneur?nios intimamente relacionada ? modula??o cortical ? revelada pela imunohistoqu?mica para as prote?nas ligantes de c?lcio calbindina (CB), calretinina (CR) e parvalbumina (PV). Em que pese a quantidade crescente de estudos focando nas prote?nas ligantes de c?lcio, o c?rtex pr?frontal de primatas ainda permanece relativamente pouco explorado, especialmente no que se refere a um melhor entendimento da organiza??o do circuito inibit?rio ao longo de suas subdivis?es. No presente estudo caracterizamos a morfologia e a distribui??o desse grupo neuronal nas regi?es medial, orbital e dorso-lateral do c?rtex pr?-frontal do sagui (Callithrix jacchus). Utilizando par?metros morfom?tricos e t?cnicas estereol?gicas, evidenciamos que os neur?nios reativos a CR (especialmente c?lulas em duplo-buqu? e bipolares) possuem arboriza??o dendr?tica mais complexa quando comparados aos neur?nios reativos a CB (neur?nios de tufos duplos e c?lulas em cesto) e PV (c?lulas em candelabro). A densidade dos neur?nios reativos a CB e CR ? mais elevada nas camadas supragranulares (II/III), enquanto os neur?nios reativos a PV se concentram predominantemente nas camadas infragranulares (V/VI). Os neur?nios reativos a CR foram o grupo predominante nas tr?s regi?es avaliadas, sendo mais prevalente na regi?o dorsolateral. Nossos achados apontam para diferen?as cruciais no circuito inibit?rio ao longo das diferentes ?reas do c?rtex pr?-frontal do sagui

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2017-06-02T21:52:23Z No. of bitstreams: 1 JoaoCarlosNascimentoDeAlencar_DISSERT.pdf: 4136417 bytes, checksum: 2e658c733e664ecd87aec927ed754f97 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2017-06-07T21:16:44Z (GMT) No. of bitstreams: 1 JoaoCarlosNascimentoDeAlencar_DISSERT.pdf: 4136417 bytes, checksum: 2e658c733e664ecd87aec927ed754f97 (MD5) / Made available in DSpace on 2017-06-07T21:16:44Z (GMT). No. of bitstreams: 1 JoaoCarlosNascimentoDeAlencar_DISSERT.pdf: 4136417 bytes, checksum: 2e658c733e664ecd87aec927ed754f97 (MD5) Previous issue date: 2017-05-09 / Sequ?ncias de est?mulos r?tmicos apresentados na faixa 125-2000ms (0.3-8Hz) podem ter efeitos importantes sobre a percep??o, motricidade e a cogni??o. A "Dynamic Attending" ? uma teoria que pressup?e a exist?ncia de oscila??es atencionais flex?veis ? sincroniza??o com eventos ambientais r?tmicos, fen?meno denominado arrastamento. A percep??o de ritmo tem sido implicada a ?reas classicamente de controle motor, notadamente os n?cleos da base. Estes n?cleos t?m sido atrelados tamb?m ao funcionamento executivo, atrav?s de la?os c?rtico-estriatais-tal?mico-corticais. Considerando as fun??es executivas sediadas no c?rtex pr?-frontal como integrantes desse circuito, o objetivo deste estudo ? caracterizar o efeito de est?mulos auditivos r?tmicos sobre par?metros de comportamento motor, desempenho cognitivo executivo e sinais eletrofisiol?gicos. A amostra (n=24) foi calculada a partir do software G*Power 3.1. Os participantes foram submetidos a tarefas de tempo motor espont?neo e tarefas de processamento executivo (soma sequencial de d?gitos), com ou sem a presen?a de pulsos sonoros isocr?nicos de tr?s diferentes intervalos. Os resultados mostram que h? sincroniza??o do per?odo motor aos pulsos com ISI (Intervalo entre est?mulos, do ingl?s, ?Inter Stimulus Interval?) igual a 500 ms, e que ISI com 350 ms ou 650 ms aumentam a variabilidade das batidas. N?o foi encontrada diferen?a entre as manipula??es experimentais no que concerne ? ativa??o auton?mica, exceto por diminui??o da frequ?ncia card?aca durante a realiza??o da tarefa com som N?o-Sincronizado 350 ms. Com rela??o aos dados eletroencefalogr?ficos, diferentes padr?es de pot?ncia espectral est?o vinculados ao intervalo de estimula??o. O ?ndice de modula??o delta-gama est? negativamente correlacionado ? taxa de acertos na condi??o 350 ms, e positivamente correlacionado na condi??o Sincronizada. O n?mero de acertos est? atrelado ao ISI, mas o Tempo de rea??o parece ter maior modula??o do ISI e do som. Nossos resultados de tempo motor espont?neo sugerem a exist?ncia de uma ?regi?o ?tima de arrastamento?, com centro em 500 ms, no qual h? maior suscetibilidade de sincroniza??o motora involunt?ria. Al?m disso, os dados indicam independ?ncia entre as fun??es executivas ?quentes? e ?frias?, e que o sistema nervoso parece acionar diferentes estrat?gias de processamento para diferentes contextos temporais do ambiente. Isto ? consistente com um modo r?tmico de processamento, que, no entanto, pode implicar em redu??o do desempenho cognitivo mediante de alta exig?ncia por velocidade de processamento. / Sequences of stimuli presented between 125-2000 ms (0.3-8Hz) may impact on perception, motor responses and cognition. Dynamic Attending Theory postulates oscillations of attention, that may synchronize by entrainment to rhythmic events from environment. Rhythm perception has been shown to involve classical motor areas, notably basal ganglia. These sub-cortical nuclei has been also linked to executive functioning, due to existence of cortical-striatum-thalamic-cortical loops. Since executive function is based on prefrontal cortex activity, this work aims to characterize effect of auditory rhythmic stimuli on motor behavior, executive function and electrophysiological responses. Sample (n=24) was previously calculated by G*Power 3.1 software. Participants were submitted to finger tapping and executive tasks (sequential arithmetic sum), while auditory tones were played or not. Our results show motor synchronization for ISI 500 ms, and increased variability for ISI 350 ms and 650 ms. Autonomic electrophysiological responses did not show any changes, except for a decreased heart rate at ISI 350 ms, Non-Synchronized Condition. Delta-Gama Modulation Index is negatively correlated with hitrate for ISI 350 ms, but positively correlated with hitrate at Synchronized Condition. ISI impacts on hitrate, but a larger modulation of both ISI and auditory stimuli over Reaction Time is shown. Our results suggest an ?optimal entrainment range?, centered at 500 ms, and an increased likelihood for involuntary synchronization at this point. Besides, results suggest so-called cold and hot executive functions are independent processes, and also that nervous system may activate different processing ways for different temporal contexts. These findings also corroborate the existence of a rhythmic processing mode, however, with decreased performance through high speed processing request.