Les noyaux Reuniens et Rhomboïde (ReRh) du thalamus, par leurs connexions denses et réciproques avec l’hippocampe (HP) et le cortex préfrontal médian (CPFm), constituent un relais clé entre ces deux structures et semblent impliqués dans les interactions HP-CPFm, support de la persistance des souvenirs. Par des approches de lésion, d’inactivation pharmacogénétique et d’imagerie cellulaire appliquées à différents paradigmes comportementaux, l’implication des noyaux ReRh dans les processus mnésiques, particulièrement de consolidation, a été évaluée. Nos travaux ont notamment mis en évidence que les noyaux ReRh, par leur implication spécifique dans les processus offline de consolidation, sont nécessaires pour la persistance à long terme d’un souvenir de peur conditionnée au contexte chez le rat. Ainsi l’implication du noyau Reuniens dans les processus de consolidation, initialement mise en évidence dans le cas de la mémoire spatiale, peut être étendue à d’autres types de mémoire HP-dépendants. / Neuroanatomical and electrophysiological data place the thalamic Reuniens and Rhomboid nuclei as a key relay between the hippocampus (HP) and the medial prefrontal cortex (mPFC), two brain structures essential for memory. As such, the ReRh nuclei are thought to be involved in HP-mPFC interactions, supporting consolidation processes, and thus memory persistence. Using excitotoxic lesion, chemogenetic inactivation and cellular imaging approaches in various behavioral paradigms, we assessed the implication of the ReRh nuclei in memory processes, particularly consolidation. Our results show that the ReRh nuclei are necessary for offline consolidation of contextual fear memory in rats. A similar conclusion has been drawn from a previous study taxing spatial memory, another HP-dependent type of memory. Thus, the present data show that the necessity of the ventral midline thalamus to systems-level consolidation is not limited to a particular type of memory but could be more general.

No description available.

Les fuseaux de sommeil sont des ondes électroencéphalographiques reflétant les mécanismes électrophysiologiques de protection du sommeil. Les adultes autistes ont un sommeil léger et moins de fuseaux de sommeil que des adultes neurotypiques. L’étude vérifie si les enfants autistes montrent également moins de fuseaux de sommeil que les enfants neurotypiques et documente leur évolution avec l’âge. Nous avons enregistré le sommeil de 34 adultes (16 autistes) et 26 enfants (13 autistes) et comparé la quantité de fuseaux de sommeil enregistrés aux électrodes préfrontales (Fp1, Fp2) et centrales (C3, C4). Les deux groupes montrent une diminution similaire des fuseaux en vieillissant. Le groupe d’enfants autistes montre moins de fuseaux que le groupe témoin aux électrodes Fp2 et C4; les adultes autistes montrent significativement moins de fuseaux que les adultes contrôles aux deux électrodes centrales. Le mauvais sommeil des autistes pourrait être causé par une faible protection du sommeil déjà présente en bas âge. / Autism is characterized by poor sleep maintenance. Sleep spindles are electroencephalographic markers representing a sleep protective mechanism. Autistic adults display less spindles than matched controls. This study investigates sleep spindle activity in children and adults with and without autism. The sleep of 34 adults (16 autistics) and 26 children (13 autistics) was recorded. Sleep spindles were counted and compared between groups at prefrontal (Fp1, Fp2) and central (C3, C4) electrodes. Both diagnostic groups showed a similar decrease in sleep spindle with age. Autistic children had significantly less spindles than controls at Fp2 and C4; adults with autism had significantly less spindles than controls at the two central electrodes. Poor sleep in children and adults with autism may be due to impaired protective mechanisms. The developmental pattern of sleep spindle topography suggests an atypical maturational course of the thalamo-cortical loop in autism.

Submitted by Fabio Sobreira Campos da Costa (fabio.sobreira@ufpe.br) on 2016-05-12T14:04:01Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Tese Luanna Moita (FINALIZADA - 20.12.15).pdf: 1634240 bytes, checksum: de4b50a363a37fcf6b9c2c50e49d910d (MD5) / Made available in DSpace on 2016-05-12T14:04:01Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Tese Luanna Moita (FINALIZADA - 20.12.15).pdf: 1634240 bytes, checksum: de4b50a363a37fcf6b9c2c50e49d910d (MD5) Previous issue date: 2015-05-13 / CAPEs / Introdução: A epilepsia do lobo temporal medial (ELTM) é o tipo de epilepsia mais comum e refratária. Apesar do nome, esta doença não está limitada ao lobo temporal, podendo também afetar o tálamo e interferir em funções cognitivas, como a linguagem. Essas implicações podem estar associadas a presença de sintomas depressivos. Objetivo: Avaliar, através de ressonância magnética quantitativa alterações estruturais do tálamo e as relacionar com variáveis clínicas, com o desempenho na linguagem e com a presença de sintomas depressivos. Metodologia: Trata-se de um estudo do tipo retrospectivo, transversal e analítico por amostra de conveniência. Os dados foram obtidos a partir de um grupo de pacientes atendidos no Hospital das Clínicas de Ribeirão Preto, da Universidade de São Paulo, no período de novembro de 2008 a 2011. A casuística foi composta por 63 pacientes (37 com lesão à direita), sendo 34 (53,96%) indivíduos do sexo feminino e 29 (46,04%) do sexo masculino, com média de idade de 41 anos (±10,14). O grupo controle foi composto por 91 indivíduos saudáveis sendo 41 (45,05%) do sexo feminino e 50 (54,95%) do sexo masculino, com média de idade de 41 anos (±17,33). Para as análises foram utilizadas medidas quantitativas de ressonância magnética do tálamo (volume, taxa de transferência da magnetização e relaxometria), dados clínicos (frequência de crise, tempo de doença e presença de sintomas depressivos), nível de escolaridade e avaliação da linguagem pelo teste de FAS e TNB. Resultados: Foi encontrado menor volume do tálamo no grupo ELTM Ipsilateral em relação ao Contralateral. Em relação aos controles, houve diferença significativa do volume do tálamo epiléptico no gênero masculino. Houve uma tendência de menor volume do tálamo com maior o tempo de doença. Já a frequência da crise não interferiu nas análises de volume dos pacientes com ELT-EH. A Transferência de Magnetização foi menor nos grupos de pacientes com ELTM Ipsilateral e Contralateral Esquerdos em relação ao Controle Esquerdo. A relaxometria foi maior no tálamo contralateral do paciente em relação ao controle. Não houve correlação da relaxometria com o tempo de doença e a frequência de crise. A doença parece interferir na capacidade de resposta ao teste FAS, visto que 94,6% dos doentes apresentam escores abaixo do esperado, o mesmo não foi observado no teste de TNB. Foi encontrado correlação dos sintomas depressivos com a relaxometria. O tálamo Ipsilateral do grupo com sintomas depressivos apresentou maior tempo de relaxometria que grupo ELTM Ipsilateral sem sintomas depressivos. Conclusão: A epilepsia do lobo temporal altera o volume e a integridade do tálamo, sendo os sintomas depressivos um fator agravante, e tal alteração parece influenciar negativamente na função da linguagem. / Introduction: Epilepsy medial temporal lobe (TLE) is the most common type of epilepsy and refractory epilepsy. Despite its name, this disease is not limited to the temporal lobe, and may also affect the thalamus and interfere with cognitive functions such as language. These implications may be associated with depressive symptoms. Objective: To evaluate, using quantitative magnetic resonance imaging of the thalamus structural changes and relate to clinical variables with performance in language and with the presence of depressive symptoms. Methodology: This is a study of retrospective type, cross-sectional analytical sample by convenience. Data were obtained from a group of patients treated at the Hospital of Ribeirão Preto, University of São Paulo, from November 2008 to 2011. The sample consisted of 63 patients (37 with injury to the right) and 34 (53.96%) females and 29 (46.04%) were male, with a mean age of 41 years (± 10.14). The control group had consisted of 91 healthy individuals and 41 (45.05%) and the 50 females (54.95%) were male, with a mean age of 41 years (± 17.33). For the analysis we used quantitative measures of magnetic resonance imaging of the thalamus (volume, throughput magnetization and relaxometry), clinical data (crisis frequency, duration of disease and presence of depressive symptoms), educational attainment and language evaluation by test FAS and TNB. Results: It was found smaller volume of the thalamus in MTLE Ipsilateral group compared to the contralateral. Regarding the controls, a significant difference from epileptic thalamic volume in males. There was a trend of lower volume of the thalamus with greater disease duration. Since the frequency of the crisis did not affect the volume of analyzes of patients with TLE-EH. The magnetization transfer was lower in groups of patients with MTLE ipsilateral and contralateral Left against the Left Control. The relaxometry was greater in the contralateral thalamus the patient compared to the control. There was no correlation of relaxometry with disease duration and frequency of crisis. The disease appears to interfere with responsiveness to FAS test, since 94.6% of patients have scores lower than expected, it was not observed in TNB test. It was found correlation of depressive symptoms with relaxometry. The ipsilateral thalamus the group with depressive symptoms had a higher time relaxometry that group MTLE Ipsilateral without depressive symptoms. Conclusion: The temporal lobe epilepsy changes the structure of the thalamus, and depressive symptoms an aggravating factor, and this change seems to influence the function of language.

本研究は、線条体パルブアルブミン発現ニューロン(PVニューロン)が受け取るグルタミン酸作動性軸索投射を順行性ウィルストレーサーを用い形態学的に調べた。その結果、運動皮質および視床腹側部からのグルタミン酸作動性軸索入力はいずれもPVニューロン樹状突起の広範囲に投射を行っているものの、視床腹側部の投射のみが細胞体から20µｍ程度の近位樹状突起に高密度な分布を示すことが明らかとなった。 / Using bacterial artificial chromosome transgenic mice expressing somatodendritic membrane–targeted green fluorescent protein in striatal parvalbumin (PV) interneurons, we demonstrate that glutamatergic inputs originating from the ventral anterior/ventral lateral motor thalamus preferentially contact on proximal dendrites, while inputs from motor cortex are uniformly distributed on PV neurons. These results were confirmed using a combination of vesicular glutamate transporter immunoreactions. Collectively, these findings suggest that PV neurons produce fast and reliable inhibition of medium spiny neurons in response to thalamic inputs. In contrast, excitatory inputs from motor cortices modulate PV dendrite excitability, possibly in concert with other glutamatergic, GABAergic, and dopaminergic inputs. / 博士(理学) / Doctor of Philosophy in Science / 同志社大学 / Doshisha University

No description available.

Deep brain stimulation (DBS) is a neurosurgical intervention now established for the treatment of movement disorders. For the treatment of chronic pain refractory to medical therapies, several prospective case series have been reported, but few centres worldwide have published findings from patients treated during the last decade using current standards of technology. This thesis seeks to survey the current clinical status of DBS for pain, investigate its mechanisms and their interactions with autonomic function, its clinical limitations and ablative alternatives. Presented first is a review of the current status of analgesic DBS including contemporary clinical studies. The historical background, scientific rationale, patient selection and assessment methods, surgical techniques and results are described. The clinical outcomes of DBS of the sensory thalamus and periventricular / periaqueductal grey (PAVG) matter in two centres are presented including results from several pain and quality of life measures. A series of translational investigations in human subjects receiving DBS for pain elucidating mechanisms of analgesic DBS and its effects upon autonomic function are then presented. Single photon emission tomography comparing PAVG, VP thalamus and dual target stimulation is described. Somatosensory and local field potential (LFP) recordings suggesting PAVG somatotopy are shown. ABPM results demonstrating changes with PAVG DBS are given and Portapres studies into heart rate variability changes with ventral PAVG DBS are detailed. Investigations using naloxone are then shown to hypothesise separate dorsal opioidergic and ventral parasympathetic analgesic streams in the PAVG. Finally, cingulotomy in lung cancer to relieve pain and dyspnoea results are discussed in the context of altering pain and autonomic function by functional neurosurgery. Pain and autonomic interactions and mechanisms in deep brain surgery for pain are then discussed alongside its limitations with proposals made for optimising treatment and improving outcomes.

O Colículo Superior (SC) é conhecido por apresentar diversas funções que modulam a caça predatória. Neste estudo, investigamos as funções do SC em ratos expostos a caça de insetos. Primeiramente, verificamos que o comportamento predatório induz uma distinta ativação da porção lateral do SC (SCl). Para entender as potenciais funções dessa região colicular, foi analisado o comportamento predatório antes e após lesões bilaterais iontoforéticas por NMDA do SCl. Animais com SCl lesados ficaram menos motivados a perseguirem as baratas, falharam para se orientarem na direção do movimento das presas e quando tentaram capturar as presas, eles apresentaram sérios déficits para capturá-las e segurá-las eficientemente. Por outro lado, animais com lesões da porção medial do SC (SCm) apresentaram apenas um aumento da latência para iniciar a caça, enquanto os outros parâmetros não diferiram significantemente dos animais intactos. Posteriormente, examinamos as conexões eferentes do SCl e do SCm usando como traçador anterógrado a leucoaglutinina do Phaseolus vulgaris. Notamos projeções densas do SCl para a região rostral da coluna lateral da matéria cinzenta periaquedutal (PAGl), um setor criticamente envolvido no controle dos aspectos motivacionais relacionados aos comportamentos de caça predatória e forrageamento. Além disso, o SCl se projeta densamente para o tálamo dorsal, especificamente para os núcleos ventral lateral, central medial e paracentral do tálamo, os quais sabemos que se projetam para setores estriatais ou para áreas motoras corticais, que provavelmente estão envolvidas no ajuste da ação motora durante a captura das presas. O SCm, por sua vez, aferenta densamente a coluna dorsolateral da PAG, núcleo cuneiforme, e núcleos reticulares mesencefálico e pontino, que são setores envolvidos na elaboração de respostas defensivas, além disso, o SCm se projeta esparsamente para os núcleos posterior lateral e suprageniculado do complexo geniculado medial / The superior colliculus is classically known to present a number of functions that fit hunting behavior. In the present study, we investigate the potential roles of the superior colliculus in rats displaying insect hunting. First, we have found that predatory hunting induces a distinct activation of the lateral region of the intermediate layer of the superior colliculus (SCl). To understand the potential roles of this collicular region, we analyzed the hunting performance before and after iontophoretic NMDA lesions bilaterally placed into the SCl. Animals with SCl lesions were clearly less motivated to pursue the roaches, failed to orient themselves toward the moving prey, and whenever the SCl-lesioned rats tried to catch the roaches, they presented serious deficits to capture and hold them efficiently. Next, we examined the SCl efferents connections using Phaseolus vulgaris leucoagglutinin as an anterograde tracer. Of particular relevance, we noted that the SCl projects to the rostral lateral periaqueductal gray, a site critically involved in controlling motivational drive to chase prey and forage. In addition, the SCl also present particularly strong projections to the dorsal thalamus, aimed at the ventral lateral, ventral medial, central medial and paracentral nuclei of thalamus, all of which known to project either to striatal sites or to cortical motor areas, likely to be involved in adjusting the motor action during prey capture. Therefore, the SCl, which seems to present cells responding to prey displacement in the temporal field, presents important arms to the periaqueductal gray and dorsal thalamic sites, influencing, respectively, the motivational drive and the motor skills to hunt

Neurons can respond to input by firing isolated action potentials or spikes. Sequences of spikes have been linked to the encoding of neuron input. However, many neurons also fire bursts; mechanistically distinct responses consisting of brief high-frequency spike firing. Bursts form separate response symbols but historically have not been thought to encode input. However, recent experimental evidence suggests that bursts can encode input in parallel with tonic spikes. The recognition of bursts as distinct encoding symbols raises important questions; these form the basic aims of this thesis: (1) What inputs do bursts encode? (2) Does burst structure provide extra information about different inputs. (3) Is burst coding robust against the presence of noise; an inherent property of all neural systems? (4) What mechanisms are responsible for burst input encoding? (5) How does burst coding manifest in in-vivo neurons. To answer these questions, bursting is studied using a combination of neuron models and in-vivo hippocampal neuron recordings. Models ranged from neuron-specific cell models to models belonging to three fundamentally different burst dynamic classes (unspecific to any neural region). These classes are defined using concepts from non-linear system theory. Together, analysing these model types with in-vivo recordings provides a specific and general analysis of burst encoding. For neuron-specific and unspecific models, a number of model types expressing different levels of biological realism are analysed. For the study of thalamic encoding, two models containing either a single simplified burst-generating current or multiple currents are used. For models simulating three burst dynamic classes, three further models of different biological complexity are used. The bursts generated by models and real neurons were analysed by assessing the input they encode using methods such as information theory, and reverse correlation. Modelled bursts were also analysed for their resilience to simulated neural noise. In all cases, inputs evoking bursts and tonic spikes were distinct. The structure of burst-evoking input depended on burst dynamic class rather than the biological complexity of models. Different n-spike bursts encoded different inputs that, if read by downstream cells, could discriminate complex input structure. In the thalamus, this n-spike burst code explains informative responses that were not due to tonic spikes. In-vivo hippocampal neurons and a pyramidal cell model both use the n-spike code to mark different LFP features. This n-spike burst may therefore be a general feature of bursting relevant to both model and in-vivo neurons. Bursts can also encode input corrupted by neural noise, often outperforming the encoding of single spikes. Both burst timing and internal structure are informative even when driven by strongly noise-corrupted input. Also, bursts induce input-dependent spike correlations that remain informative despite strong added noise. As a result, bursts endow their constituent spikes with extra information that would be lost if tonic spikes were considered the only informative responses.

Introdução. Nos últimos a função motora vem sendo associada com a atenuação sensitiva e de dor, logo antes, durante e apos a contração muscular. No entanto as vias anatômicas e funcionais deste fenômeno não são conhecidas. O objetivo deste estudo é o de criar um modelo animal e investigar o efeito da estimulação subliminar do córtex motor (ECM) no limiar nociceptivo e na atividade neuronal subcortical. Método. O limiar nociceptivo foi avaliado por teste plantar e reflexo de retirada da cauda antes e após o implante dos eletródios epidurais sobre o córtex motor da pata posterior orientado por mapa funcional na mesma cepa de ratos. Os mesmos testes foram repetidos antes, durante e após a ECM. Antagonismo sistêmico do por naloxona foi incluído neste protocolo para investigar a relação com mediação opióide. O registro neuronal multiunitário do núcleo centro mediano (CM) e ventral posterolateral (VPL) do tálamo e da substância periaqüeductal (SPM) foi realizado antes, durante e após ECM ipso e contralateral. Resultados. O implante per se não causou alterações no limiar nociceptivo. ECM induziu significativa antinocicepção seletiva na pata contralateral mas não na ipsolateral. Este efeito não mais foi observado 15 minutos após o término da estimulação. Nenhuma alteração motora e comportamental foi observada nos testes de campo aberto. A mesma estimulação no córtex sensitivo e parietal posterior não causou quaisquer alterações de limiar nociceptivo. Administração sistêmica de naloxone reverteu completamente o efeito antes observado com a ECM. O registro neuronal multiunitário evidenciou diminuição na atividade do CM durante e após a ECM contra e ipsolateral. O ritmo de disparos neuronais no VPL também mostrou diminuição apenas com a ECM ipsolateral. No entanto os neurônios da SPM aumentaram significativamente a freqüência de disparos com ECM ipsolateral e não com a contralateral. Conclusão. A ECM subliminar está relacionada consistentemente com a atenuação sensitiva durante o comportamento, provavelmente mediado por inibição talâmica e ativação da SPM. / Background. The motor function has been associated to sensory and pain attenuation, before during and shortly after the muscle activity. How ever the anatomical and functional basis of this phenomenon is not yet defined. The present study was designed to set an animal model and investigate the effect of subthreshold electrical stimulation of motor cortex (MCS) on pain threshold and neuron activity of thalamus and periaqüedutal gray. Method. Nociceptive thresholds of hind paws and the tail flick reflex were evaluated before and after surgical placement of epidural electrodes; before during and after electrical stimulation of motor cortex. Opioid antagonism was also included in this protocol in order to define neurotransmitter mediation of this process. Multiunit recording of thalamic median center (CM) and ventral posterolateral nuclei (VPL) and lateral periaqüedutal gray (SPM) were performed before and after electrical stimulation of ipso and contralateral motor cortex. Results. The procedure itself did not induce any threshold changes. MCS induced selective antinociception of contralateral paw, but no changes were detected in the nociceptive threshold of the ipsolateral side. This effect disappeared completely 15 minutes after the stimulation was ceased. No behavioral or motor impairment were observed during and after the stimulation session in the open field test. The same stimulation on sensory and posterior parietal cortex did not elicit any changes in behavioral and nociceptive tests. Systemic administration of naloxone completely reversed the previous observed antinociceptive effect. Multiunit recording evidenced decrease in spontaneous neuron firing in CM with short recovery time during ipso and contralateral MCS. Neuron activity in VPL was also significantly decreased during ipsolateral MCS but not with contralateral stimulation. How ever, neuron firing in SPM was significantly increased during and long after ipsolateral MCS but not with contralateral stimulation. Conclusion. Subthreshold MCS is consistently related to sensory attenuation during behavior, probably through thalamic inhibition and SPM activation.