Theta-associated high-frequency oscillations (110–160 Hz) in the hippocampus and neocortex

TORT, A. B. L. ; SCHEFFER-TEIXEIRA, R ; Souza, B.C. ; DRAGUHN, A. ; BRANKACK, J. . Theta-associated high-frequency oscillations (110-160 Hz) in the hippocampus and neocortex. Progress in Neurobiology , v. 100, p. 1-14, 2013.

Selective Coupling between Theta Phase and Neocortical Fast Gamma Oscillations during REM-Sleep in Mice

TORT, A. B. L. ; SCHEFFER-TEIXEIRA, R ; Souza, B.C. ; DRAGUHN, A. ; BRANKACK, J. . Theta-associated high-frequency oscillations (110-160 Hz) in the hippocampus and neocortex. Progress in Neurobiology , v. 100, p. 1-14, 2013.

Abordagem de pacientes autistas em Odontopediatria

O autismo é uma condição que faz parte de um grupo de perturbações do desenvolvimento global das funções cerebrais e que, por regra, é diagnosticada no início da infância. A dificuldade na linguagem e comunicação, o défice na interação social, as esteriotipias e os interesses específicos e comportamentos repetitivos caracterizam os indivíduos portadores desta patologia. A saúde oral das crianças autistas é geralmente precária e as necessidades de tratamento dentário elevadas. No entanto, os problemas comportamentais destes doentes fazem com que os pais não recorram às consultas de medicina dentária, outras vezes quando recorrem à consulta as dificuldades de colaboração impedem a prestação de cuidados de saúde oral adequados a estas crianças. Pretendeu-se assim, com este trabalho, realizar uma revisão sistemática de literatura científica, publicada nos últimos 15 anos, acerca dos problemas orais que atingem os pacientes autistas, e simultaneamente, compilar diretrizes de atuação clínica para orientar o médico dentista no atendimento destes doentes. Para isto, durante os meses de Outubro de 2014 a Outubro de 2015, procedeu-se a uma pesquisa bibliográfica nas bases de dados PubMed e B-on, sendo consultados também outros bancos de dados como LILACS – BIREME, SciELO, utilizando as seguintes palavras-chave: “autism”, “pediatric dentistry”, “Asperger Syndrome”, “Rett Syndrome”, “Childhood Disintegrative Disorder”, “prevalence”, “neurobiology”, “etiology”, “diagnosis”, “diagnostic criteria”, “comorbidity”, “oral health”, “dental caries”, “periodontal disease”, “oral habits”, “bruxism”, “self-injury”, “dental trauma”, “dental injury”, “malocclusion”, “behavior management techniques” separadas ou associadas pelo operador de pesquisa booleano AND. Na pesquisa foram empregues os seguintes limites: artigos publicados nos últimos 15 anos, abstract disponível, estudos em humanos e artigos e língua inglesa, francesa, portuguesa e espanhola. Desta pesquisa resultou um total de 150 artigos que foram selecionados primeiramente pelos títulos, seguidamente pela leitura dos abstracts e, finalmente, do artigo por inteiro, obtendo-se assim 95 artigos, para revisão. Foram ainda considerados artigos de referência publicados em anos anteriores, livros de texto médicos e publicações portuguesas com dados epidemiológicos sobre as Perturbações do Espetro do Autismo em Portugal. As doenças orais encontradas nas crianças autistas são semelhantes às das crianças sem qualquer perturbação mental, contudo a preferência por alimentos cariogénicos, a diminuição do fluxo salivar induzida pelos fármacos, associadas a uma pobre higiene oral, justificam uma maior prevalência de cárie. As doenças periodontais, também muito prevalentes neste grupo, desenvolvem-se em virtude da combinação da falta de hábitos de higiene oral, com os efeitos secundários de fármacos administrados a estes doentes, como os anticonvulsivantes. No seu atendimento na consulta dentária recorre-se às mesmas estratégias de orientação de comportamento aplicadas nas crianças saudáveis, para contornar os sentimentos de medo, ansiedade, desconfiança e a incapacidade de interação social, e assim evitar comportamentos de recusa durante a consulta dentária. É no entanto de salientar que os distúrbios comportamentais, o défice da comunicação e a falta de capacidades de interação social, caraterísticas do autismo impossibilitam a eficácia das técnicas de controlo do comportamento comunicativas, obrigando, muitas vezes, ao uso de técnicas de controlo de comportamento avançadas para prestação de cuidados de saúde oral com eficácia e em segurança. É importante uma grande motivação de pais/responsáveis para a saúde e higiene oral das crianças com Perturbações do Espetro do Autismo, e que todos os profissionais de saúde envolvidos no cuidado destes doentes contribuam para a aprendizagem de comportamentos que promovam a saúde oral destes doentes.

Changes in peak expiratory flow and respiratory strength during the menstrual cycle

This study evaluated the spirometry and respiratory static pressures in 17 young women, twice a week for three successive ovulatory menstrual cycles to determine if such variables changed across the menstrual, follicular, periovulatory, early-tomid luteal and late luteal phases. The factors phases of menstrual cycle and individual cycles had no significant effect on the spirometry variables except for peak expiratory flow (PEF) and respiratory static pressures. Significant weak positive correlations were found between the progesterone:estradiol ratio and PEF and between estrogen and tidal volume (r = 0.37), inspiratory time (r = 0.22), expiratory time (r = 0.19), maximal inspiratory pressure (r = 0.25) and maximal expiratory pressure (r = 0.20) and for progesterone and maximal inspiratory pressure (r = 0.32) during the early-to-mid luteal phase. Although most parameters of the spirometry results did not change during the menstrual cycle, the correlations observed between sexual hormones and respiratory control variables suggest a positive influence of sexual female hormones controlling the thoracic pump muscles in the luteal phase

Theta-associated high-frequency oscillations (110–160 Hz) in the hippocampus and neocortex

TORT, A. B. L. ; SCHEFFER-TEIXEIRA, R ; Souza, B.C. ; DRAGUHN, A. ; BRANKACK, J. . Theta-associated high-frequency oscillations (110-160 Hz) in the hippocampus and neocortex. Progress in Neurobiology , v. 100, p. 1-14, 2013.

Selective Coupling between Theta Phase and Neocortical Fast Gamma Oscillations during REM-Sleep in Mice

TORT, A. B. L. ; SCHEFFER-TEIXEIRA, R ; Souza, B.C. ; DRAGUHN, A. ; BRANKACK, J. . Theta-associated high-frequency oscillations (110-160 Hz) in the hippocampus and neocortex. Progress in Neurobiology , v. 100, p. 1-14, 2013.

The interplay between neuronal activity and actin dynamics mimic the setting of an LTD synaptic tag

Persistent forms of plasticity, such as long-term depression (LTD), are dependent on the interplay between activity-dependent synaptic tags and the capture of plasticity-related proteins. We propose that the synaptic tag represents a structural alteration that turns synapses permissive to change. We found that modulation of actin dynamics has different roles in the induction and maintenance of LTD. Inhibition of either actin depolymerisation or polymerization blocks LTD induction whereas only the inhibition of actin depolymerisation blocks LTD maintenance. Interestingly, we found that actin depolymerisation and CaMKII activation are involved in LTD synaptic-tagging and capture. Moreover, inhibition of actin polymerisation mimics the setting of a synaptic tag, in an activity-dependent manner, allowing the expression of LTD in non-stimulated synapses. Suspending synaptic activation also restricts the time window of synaptic capture, which can be restored by inhibiting actin polymerization. Our results support our hypothesis that modulation of the actin cytoskeleton provides an input-specific signal for synaptic protein capture.

Sensory gating and its modulation by cannabinoids: electrophysiological, computational and mathematical analysis

Gating of sensory information can be assessed using an auditory conditioning-test paradigm which measures the reduction in the auditory evoked response to a test stimulus following an initial conditioning stimulus. Recording brainwaves from specific areas of the brain using multiple electrodes is helpful in the study of the neurobiology of sensory gating. In this paper, we use such technology to investigate the role of cannabinoids in sensory gating in the CA3 region of the rat hippocampus. Our experimental results show that application of the exogenous cannabinoid agonist WIN55,212-2 can abolish sensory gating. We have developed a phenomenological model of cannabinoid dynamics incorporated within a spiking neural network model of CA3 with synaptically interacting pyramidal and basket cells. Direct numerical simulations of this model suggest that the basic mechanism for this effect can be traced to the suppression of inhibition of slow GABAB synapses. Furthermore, by working with a simpler mathematical firing rate model we are able to show the robustness of this mechanism for the abolition of sensory gating.

Delays in activity based neural networks

In this paper we study the effect of two distinct discrete delays on the dynamics of a Wilson-Cowan neural network. This activity based model describes the dynamics of synaptically interacting excitatory and inhibitory neuronal populations. We discuss the interpretation of the delays in the language of neurobiology and show how they can contribute to the generation of network rhythms. First we focus on the use of linear stability theory to show how to destabilise a fixed point, leading to the onset of oscillatory behaviour. Next we show for the choice of a Heaviside nonlinearity for the firing rate that such emergent oscillations can be either synchronous or anti-synchronous depending on whether inhibition or excitation dominates the network architecture. To probe the behaviour of smooth (sigmoidal) nonlinear firing rates we use a mixture of numerical bifurcation analysis and direct simulations, and uncover parameter windows that support chaotic behaviour. Finally we comment on the role of delays in the generation of bursting oscillations, and discuss natural extensions of the work in this paper.

OPA1-related disorders: Diversity of clinical expression, modes of inheritance and pathophysiology

International audience

A perfect day for zebrafish : neuromodulation of sleep in a diurnal vertebrate

Every day, we shift among various states of sleep and arousal to meet the many demands of our bodies and environment. A central puzzle in neurobiology is how the brain controls these behavioral states, which are essential to an animal's well-being and survival. Mammalian models have predominated sleep and arousal research, although in the past decade, invertebrate models have made significant contributions to our understanding of the genetic underpinnings of behavioral states. More recently, the zebrafish (Danio rerio), a diurnal vertebrate, has emerged as a promising model system for sleep and arousal research.

In this thesis, I describe two studies on sleep/arousal pathways that I conducted using zebrafish, and I discuss how the findings can be combined in future projects to advance our understanding of vertebrate sleep/arousal pathways. In the first study, I discovered a neuropeptide that regulates zebrafish sleep and arousal as a result of a large-scale effort to identify molecules that regulate behavioral states. Taking advantage of facile zebrafish genetics, I constructed mutants for the three known receptors of this peptide and identified the one receptor that exclusively mediates the observed behavioral effects. I further show that the peptide exerts its behavioral effects independently of signaling at a key module of a neuroendocrine signaling pathway. This finding contradicts the hypothesis put forth in mammalian systems that the peptide acts through the classical neuroendocrine pathway; our data further generate new testable hypotheses for determining the central nervous system or alternative neuroendocrine pathways involved.

Second, I will present the development of a chemigenetic method to non-invasively manipulate neurons in the behaving zebrafish. I validated this technique by expressing and inducing the chemigenetic tool in a restricted population of sleep-regulating neurons in the zebrafish. As predicted by established models of this vertebrate sleep regulator, chemigenetic activation of these neurons induced hyperactivity, whereas chemigenetic ablation of these neurons induced increased sleep behavior. Given that light is a potent modulator of behavior in zebrafish, our proof-of-principle data provide a springboard for future studies of sleep/arousal and other light-dependent behaviors to interrogate genetically-defined populations of neurons independently of optogenetic tools.

Neuroimaging of the human brain in adolescent substance users

Included among the topics: Cognitive development, learning, and drug use. Neurobiology of the action of drugs of abuse. Findings in adolescents with substance dependence based on neuroimaging tests.

Early origins of mental disorder - risk factors in the perinatal and infant period

BACKGROUND: There is increasing understanding of the significance of early neurodevelopment in establishing risk for the range of mental disorders. Models of the early aetiology of mental disorders are complex with a range of potential factors from genetic and epigenetic to environmental influencing neurological and psychological development. Whilst the mechanisms are not fully understood, this paper provides an overview of potential biological and neurobiological factors that might be involved. METHOD: An aetiological model is presented and discussed. The discussion includes a range of risk factors for mental disorder. Maternal anxiety disorder is presented and reviewed as an example of the interaction of placental, epigenetic and early parenting factors elevating risk of poor neonatal outcome. RESULTS: Available evidence points to the importance of in-utero influences as well as the role of early attachment and emotional care. Transgenerational mechanisms such as the impact of maternal mental disorder on foetal development are important models for examination of early risk. Maternal anxiety, as an example, is a significant risk factor for compromised mental health. CONCLUSIONS: Development of models for understanding the early origins of mental disorder is an important step in elaborating risk reduction strategies. Comprehensive early identification of risk raises the possibility of preventive interventions.

Mitochondrial dysfunction in bipolar disorder: evidence, pathophysiology and translational implications

Bipolar disorder (BD) is a chronic psychiatric illness characterized by severe and biphasic changes in mood. Several pathophysiological mechanisms have been hypothesized to underpin the neurobiology of BD, including the presence of mitochondrial dysfunction. A confluence of evidence points to an underlying dysfunction of mitochondria, including decreases in mitochondrial respiration, high-energy phosphates and pH; changes in mitochondrial morphology; increases in mitochondrial DNA polymorphisms; and downregulation of nuclear mRNA molecules and proteins involved in mitochondrial respiration. Mitochondria play a pivotal role in neuronal cell survival or death as regulators of both energy metabolism and cell survival and death pathways. Thus, in this review, we discuss the genetic and physiological components of mitochondria and the evidence for mitochondrial abnormalities in BD. The final part of this review discusses mitochondria as a potential target of therapeutic interventions in BD.

Relationship between erythrocyte fatty acid composition and psychopathology in the Vienna omega-3 study

This study investigated the relationship between erythrocyte membrane fatty acid (FA) levels and the severity of symptoms of individuals at ultra-high risk (UHR) for psychosis. Subjects of the present study consisted of 80 neuroleptic-naïve UHR patients. Partial correlation coefficients were calculated between baseline erythrocyte membrane FA levels, measured by gas chromatography, and scores on the Positive and Negative Syndrome Scale (PANSS), Global Assessment of Functioning Scale, and Montgomery-Asberg Depression Rating Scale (MADRS) after controlling for age, sex, smoking and cannabis use. Subjects were divided into three groups according to the predominance of positive or negative symptoms based on PANSS subscale scores; membrane FA levels in the three groups were then compared. More severe negative symptoms measured by PANSS were negatively correlated with two saturated FAs (myristic and margaric acids), one ω-9 monounsaturated FA (MUFA; nervonic acid), and one ω-3 polyunsaturated FA (PUFA; docosapentaenoic acid), and were positively correlated with two ω-9 MUFAs (eicosenoic and erucic acids) and two ω-6 PUFAs (γ-linolenic and docosadienoic acids). More severe positive symptoms measured by PANSS were correlated only with nervonic acid. No associations were observed between FAs and MADRS scores. In subjects with predominant negative symptoms, the sum of the ω-9 MUFAs and the ω-6:ω-3 FA ratio were both significantly higher than in those with predominant positive symptoms, whereas the sum of ω-3 PUFAs was significantly lower. In conclusion, abnormalities in FA metabolism may contribute to the neurobiology of psychopathology in UHR individuals. In particular, membrane FA alterations may play a role in negative symptoms, which are primary psychopathological manifestations of schizophrenia-related disability.