Neuronal - Glia Interactions

Este e-book apresenta uma introdução acessível e didática às redes neurais artificiais, com foco na aplicação em contextos de ensino. A obra explora conceitos fundamentais, arquiteturas e algoritmos de treino, ilustrando cada tópico com exemplos claros e exercícios práticos. O conteúdo é adequado para estudantes e professores interessados em compreender os princípios e aplicações desta área da Inteligência Artificial, facilitando a integração de redes neurais em projetos e atividades de sala de aula.

Axon regrowth after spinal cord injury (SCI) is inhibited by several types of inhibitory extracellular molecules in the central nervous system (CNS), including chondroitin sulfate proteoglycans (CSPGs), which also are components of perineuronal nets (PNNs). The axons of lampreys regenerate following SCI, even though their spinal cords contain CSPGs, and their neurons are enwrapped by PNNs. Previously, we showed that by 2 weeks after spinal cord transection in the lamprey, expression of CSPGs increased in the lesion site, and thereafter, decreased to pre-injury levels by 10 weeks. Enzymatic digestion of CSPGs in the lesion site with chondroitinase ABC (ChABC) enhanced axonal regeneration after SCI and reduced retrograde neuronal death. Lecticans (aggrecan, versican, neurocan, and brevican) are the major CSPG family in the CNS. Previously, we cloned a cDNA fragment that lies in the most conserved link-domain of the lamprey lecticans and found that lectican mRNAs are expressed widely i...

Neuropathologe Der in der hirnpathologischen Schule von Gerd Peters (1906-1987) in Bonn ausgebildete Neuropathologe Georg W. Kreutzberg beschäftigte sich Zeit seines Lebens mit der De-und Regeneration des Nervensystems in zellpathologischer, methodologischer und anwendungsbezogener Hinsicht. In diesem Zusammenhang entdeckte er in den späten 1960er Jahren, dass nach neurodegenerativen Veränderungen des Zentralen Nervensystems vermehrt perineuronale Wachstumsprozesse auftraten, die sich besonders auf eine Mikrogliazellvermehrung im Neuropil nichtmyelinisierter Axone und Dendritenfortsätze zurückführen ließen.

Norepinephrine (NE) is widely distributed throughout the brain. It modulates intrinsic currents, as well as amplitude and frequency of synaptic transmission affecting the 'signal-to-noise ratio' of sensory responses. In the visual cortex, a 1-and b-adrenergic receptors (AR) gate opposing effects on long-term plasticity of excitatory transmission. Whether and how NE recruits these plastic mechanisms is not clear. Here, we show that NE modulates glutamatergic inputs with different efficacies for a 1-and bAR. As a consequence, the priming of synapses with different NE concentrations produces dose-dependent competing effects that determine the temporal window of spike-timing dependent plasticity (STDP). While a low NE concentration leads to long-term depression (LTD) over broad positive and negative delays, a high NE concentration results in bidirectional STDP restricted to very narrow intervals. These results indicate that the local availability of NE, released during emotional arousal, determines the compound modulatory effect and the output of STDP.

Análise e Desenvolvimento de Sistemas vs. Neuropróteses na Reabilitação Humana: Uma Abstração.

A interseção entre Análise e Desenvolvimento de Sistemas (ADS) e Neuropróteses na Reabilitação Humana representa uma das fronteiras mais promissoras da tecnologia e da saúde.

Embora pareçam campos distintos, a verdade é que o sucesso e a evolução das neuropróteses dependem fundamentalmente da expertise em ADS.

Análise e Desenvolvimento de Sistemas é a espinha dorsal tecnológica que viabiliza, aprimora e torna inteligentes as Neuropróteses.
Sem a capacidade de projetar, construir e otimizar os sistemas de software e hardware que as controlam e as tornam responsivas, as neuropróteses seriam meros componentes eletrônicos estáticos.
A simbiose entre esses dois campos é o que impulsiona a inovação na reabilitação, oferecendo novas esperanças e possibilidades para milhões de pessoas em todo o mundo.
É a engenharia de software e de sistemas que dá vida à promessa da neurotecnologia, transformando sinais biológicos em movimentos e sensações restauradas.

By Rodolfo Wollny - 2025

Studies have implicated astrocytic dysfunction in Alzheimer's disease (AD). However, the role of astrocytes in the pathophysiology and treatment of the disease is poorly characterized. Here, we identified astrocytes as independent key factors involved in several Alzheimer-like phenotypes in an APP/PS1 mouse model, including amyloid pathology, altered neuronal and synaptic properties, and impaired cognition. In vitro astrocytes from APP/PS1 mice induced synaptotoxicity as well as reduced dendritic complexity and axonal branching of hippocampal neurons. These astrocytes produced high levels of soluble b-amyloid (Ab) which could be significantly inhibited by fluoxetine (FLX) via activating serotonin 5-HT 2 receptors. FLX could also protect hippocampal neurons against astrocyte-induced neuronal damage in vitro. In the same APP/PS1 mice, FLX inhibited activation of astrocytes, lowered Ab products, ameliorated neurotoxicity, and improved behavioral performance. These findings may provide a basis for the clinical application of FLX in patients, and may also lay the groundwork for exploration of other novel astrocyte-based therapies of AD.

T he use of transgenic mice to elucidate Alzheimer's disease has been development in the last decade. Here we use APP/ Preseniline 1 transgenic mice to analyze inflammation and oxidative stress in transgenic mice compared with wild type. Microarray from inflammation proteins, Western-blot and RT-PCR are used to compare wild type and transgenic mice. Increase in pro-inflammatory proteins and decrease in anti-inflammatory proteins were detected in transgenic compared with wild type. Also, using western-blot assay we detect an increase of NMDA R1 and a decrease of NMDA R2 in transgenic mice compared with wild type in hippocampus, limbic and cerebellum. In conclusion, an unbalance between inflammatory and anti-inflammatory proteins and also different regions in brain use different pathways to protect viability of cell brain against the toxicity in Alzheimer's disease.

Changes in extracellular potassium ([K + ] e) modulate neuronal networks via changes in membrane potential, voltage-gated channel activity and alteration of transmission at the synapse. Given the limited extracellular space in the CNS, potassium clearance is crucial. As activityinduced potassium transients are rapidly managed by astrocytic Kir4.1 and astrocyte-specific Na + /K +-ATPase (NKA), any neurotransmitter/neuromodulator that can regulate their function may have indirect influence on network activity. Neuromodulators differentially affect cortical/thalamic networks to align sensory processing with differing behavioral states. Given serotonin (5HT), norepinephrine (NE), and acetylcholine (ACh) differentially affect spike frequency adaptation and signal fidelity ("signal-to-noise") in somatosensory cortex, we hypothesize that [K + ] e may be differentially regulated by the different neuromodulators to exert their individual effects on network function. This study aimed to compare effects of individually applied 5HT, NE, and ACh on regulating [K + ] e in connection to effects on cortical evoked response amplitude and adaptation in male mice. Using extracellular field and K + ion-selective recordings of somatosensory stimulation, we found that differential effects of 5HT, NE, and ACh on [K + ] e regulation mirrored differential effects on amplitude and adaptation. 5HT effects on transient K + recovery, adaptation and field post-synaptic potential amplitude were disrupted by barium (200 µM), whereas NE and ACh effects were disrupted by ouabain (1 µM) or iodoacetate (100 µM). Considering the impact [K + ] e can have on many network functions; it seems highly efficient that neuromodulators regulate [K + ] e to exert their many effects. This study provides functional significance for astrocyte-mediated buffering of [K + ] e in neuromodulator-mediated shaping of cortical network activity. Significance statement We demonstrate that the neuromodulators serotonin, norepinephrine, and acetylcholine all have distinct effects on astrocyte-mediated extracellular potassium regulation and that these differential actions are associated with the different effects of the neuromodulators on cortical networks. By affecting astrocytic potassium regulation, long-range neuromodulatory networks can rapidly and efficiently affect broad areas of the brain. Given that neuromodulatory networks are at the core of our behavioral state and determine how we interact with our environment, these studies highlight the importance of basic astrocyte function in general cognition and psychiatric disorders. .

Resumo Este artigo explora a evolução, os sucessos e fracassos da Inteligência Artificial (IA), destacando as oportunidades futuras e os desafios regulatórios. A análise visa fornecer uma compreensão ampla sobre a eficácia das iniciativas de IA e suas implicações para empresários e líderes.

This article explores the evolution, successes and failures of Artificial Intelligence (AI), highlighting future opportunities and regulatory challenges. The analysis aims to provide a broad understanding of the effectiveness of AI initiatives and their implications for business owners and leaders. * Mestre em computação comênfase em sistemas de apoio a decisão

Following the oral administration of disulfiram to alcoholic patient volunteers, methyl diethyldithiocarbamate (MeDDC) was noted in blood withdrawn between one and two hours after dosing. This is consistent with previous reports of McDDC in mice and dogs. It is suggested that McDDC is an intermediate in the formation of urinary sulfate .

A atual capacidade computacional tem possibilitado o desenvolvimento constante de ferramentas de apoio a melhoria continua dos processos industriais, onde as Redes Neurais Artificiais (RNAs) merecem especial destaque. Diante disso, o presente artigo tem como objetivo apresentar uma revisao bibliografica acerca dos principais conceitos, caracteristicas e principios relacionados as RNAs, com enfoque em suas aplicacoes praticas. E possivel identificar tres classes de arquitetura de redes neurais fundamentalmente diferentes: redes alimentadas adiante com camada unica, redes alimentadas diretamente com multiplas camadas e redes recorrentes, sendo sua definicao de fundamental importância para a eficiencia do processo ao qual se destina. O processo de aprendizagem de uma RNA pode ocorrer de duas maneiras distintas: aprendizado supervisionado e aprendizado nao supervisionado, tendo como principal diferenca a presenca ou nao de um supervisor externo. Uma das principais vantagens da RNA e a c...

Backround Both type 2 diabetes (T2D) and Alzheimer's disease affect large number of people all over the world, especially in developed countries, and involve common molecular mechanisms in degenerative processes. Aim Our study is to investigate the expression levels of the ADAMTS4, TIMP3, RELN, and BCAN genes which encode extracellular matrix molecules and are thought to be related to the pathophysiology of Alzheimer's disease in rats that we used to develop a T2D model by injection of a streptozotocin (STZ) and feeding with high-fat diet (HFD). Material and methods In total, 40 rats were divided into four groups: HFD + STZ (10), HFD (10), STZ (10), and the control (10). The weight and blood glucose levels of all rats were recorded, and the insulin tolerance test was performed. At the end of the experimental period, the hippocampus of the rats was isolated and a part of this was used for gene expression analysis through real-time PCR, whereas other parts were used for histological analyses. Results Our results show that plaque-like structures were found in the histological examination of the experimental T2D model. In molecular studies, the expression levels of the ADAMTS4, TIMP3, RELN, and BCAN genes were decreased in the HFD +STZ and STZ groups compared with the control, whereas the same expression levels, except that of inhibitor TIMP3, were found to increase in the HFD group. Conclusion These genes encoding proteases that regulate neuronal activity have decreased levels in the T2D model. There may be potential in the adoption of new treatment approaches for Alzheimer's and T2D.

The pathophysiological process of Alzheimer's disease (AD) is believed to begin many years before the formal diagnosis of AD dementia. This protracted preclinical phase offers a crucial window for potential therapeutic interventions, yet its comprehensive characterization remains elusive. Accumulating evidence suggests that amyloid-β (Aβ) may mediate neuronal hyperactivity in circuit dysfunction in the early stages of AD. At the same time, neural activity can also facilitate Aβ accumulation through intricate feed-forward interactions, complicating elucidating the conditions governing Aβ-dependent hyperactivity and its diagnostic utility. In this study, we use biophysical modeling to shed light on such conditions. Our analysis reveals that the inherently nonlinear nature of the underlying molecular interactions can give rise to the emergence of various modes of hyperactivity. This diversity in the mechanisms of hyperactivity may ultimately account for a spectrum of AD manifestations.

Astrocytes are now viewed as key elements of brain wiring as well as neuronal communication. Indeed, they not only bridge the gap between metabolic supplies by blood vessels and neurons, but also allow fine control of neurotransmission by providing appropriate signaling molecules and insulation through a tight enwrapping of synapses. Recognition that astroglia is essential to neuronal communication is nevertheless fairly recent and the large body of evidence dissecting such role has focused on the synaptic level by identifying neuro-and gliotransmitters uptaken and released at synaptic or extrasynaptic sites. Yet, more integrated research deciphering the impact of astroglial functions on neuronal network activity have led to the reasonable assumption that the role of astrocytes in supervising synaptic activity translates in influencing neuronal processing and cognitive functions. Several investigations using recent genetic tools now support this notion by showing that inactivating or boosting astroglial function directly affects cognitive abilities. Accordingly, brain diseases resulting in impaired cognitive functions have seen their physiopathological mechanisms revisited in light of this primary protagonist of brain processing. We here provide a review of the current knowledge on the role of astrocytes in cognition and in several brain diseases including neurodegenerative disorders, psychiatric illnesses, as well as other conditions such as epilepsy. Potential astroglial therapeutic targets are also discussed.

Individuals with autism spectrum disorders (ASDs) exhibit atypical sensory characteristics, impaired social skills, deficits in verbal and nonverbal communication, and restricted and repetitive behaviors. The relationship between sensory characteristics and brain morphological changes in ASD remains unclear. In this study, we investigated the association between brain morphological changes and sensory characteristics in individuals with ASD using brain image analysis and a sensory profile test. Forty-three adults with ASD and 84 adults with typical development underwent brain image analysis using FreeSurfer. The brain cortex was divided into 64 regions, and the cortical thickness and volume of the limbic system were calculated. The sensory characteristics of the participants were evaluated using the Adolescent/Adult Sensory Profile (AASP). Correlation analysis was performed for cortical thickness, limbic area volume, and AASP scores. In the ASD group, there was a significant positive correlation between visual sensory sensitivity scores and the right lingual cortical thickness (r = 0.500). There were also significant negative correlations between visual sensation avoiding scores and the right lateral orbitofrontal cortical thickness (r = −0.513), taste/smell sensation avoiding scores and the right hippocampal volume (r = −0.510), and taste/smell sensation avoiding scores and the left hippocampal volume (r = −0.540). The study identified associations among the lingual cortical thickness, lateral orbitofrontal cortical thickness, and hippocampal volume and sensory characteristics. These findings suggest that brain morphological changes may trigger sensory symptoms in adults with ASD.

There is increasing evidence that oxidative stress (OS) and neuroinflammation play a role in the neuroprogression of schizophrenia (SCZ). Promising novel candidates which have been proposed in the search for biomarkers of psychotic illness include NADPH oxidase 1,2 (NOX1,2) and raftlin. NOX1 from the NOX family is the main source of physiological reactive oxygen species (ROS) and raftlin, the main lipid raft protein, is associated with inflammatory processes. The aim of the present study was to evaluate serum NOX1 and raftlin levels in chronic stable patients with SCZ. Methods: We measured serum NOX1 and raftlin levels from 45 clinically stable patients with SCZ and 45 healthy controls (HCs) matched for age, sex, and body-mass index. The Positive and Negative Syndrome Scale was applied to the patient group to evaluate the severity of psychotic symptoms. Results: NOX1 and raftlin levels in the patients were statistically significantly higher than the HCs (NOX1 p<0.001, raftlin p<0.001). Both parameters showed very good diagnostic performance (NOX1 AUC = 0.931, raftlin AUC = 0.915). We obtained positive and significant correlations between serum levels of both biomarkers and symptom severity. Discussion: This preliminary study indicating elevations in serum NOX1 and raftlin levels in patients with SCZ supports the importance of OS and inflammatory processes in the etiopathogenesis of the illness.

Substance use disorders are a global health problem with increasing prevalence resulting in significant socioeconomic burden and increased mortality. Converging lines of evidence point to a critical role of brain extracellular matrix (ECM) molecules in the pathophysiology of substance use disorders. An increasing number of preclinical studies highlight the ECM as a promising target for development of novel cessation pharmacotherapies. The brain ECM is dynamically regulated during learning and memory processes, thus the time course of ECM alterations in substance use disorders is a critical factor that may impact interpretation of the current studies and development of pharmacological therapies. This review highlights the evidence for the involvement of ECM molecules in reward learning, including drug reward and natural reward such as food, as well as evidence regarding the pathophysiological state of the brain’s ECM in substance use disorders and metabolic disorders. We focus on the...

The application of physico-chemical principles has been routinely used to explain various physiological concepts. The Nernst equation is one example of this, used to predict the potential difference created by the transmembrane ion gradient resulting from uneven ion distribution within cellular compartments and the interstitial space. This relationship remains of fundamental importance to the understanding of electrical signaling in the brain, which relies on current flow across cell membranes. We describe four distinct occasions when the Nernst equation was ingeniously applied in experimental design to illuminate diverse cellular functions, from the dependence of the action potential on Na+ influx to K+ buffering in astrocytes. These examples are discussed with the aim of inspiring students to appreciate how the application of seemingly textbook-bound concepts can dictate novel experimental design across physiological disciplines.

Uma Memória Associativa (AM, Associative Memory)é um modelo projetado para armazenar pares de entrada e saída. Sobretudo, uma AM deve ser capaz de recordar uma saída desejada mesmo após a apresentação de uma versão incompleta ou distorcida de um padrão de entrada. Essa tese de doutorado discute as Memórias Associativas Morfológicas Nebulosas (FMAMs, Fuzzy Morphological Associative Memories), uma classe de memórias associativas elaboradas para armazenar padrões nebulosos e descritas por redes neurais nebulosas cujos neurônios realizam operações elementares da morfologia matemática, i.e., dilatação, erosão, anti-dilatação e anti-erosão.É verificado que os principais modelos de Memória Associativa Nebulosa (FAM, Fuzzy Associative Memory) pertencemà classe das FMAMs. Essa tese introduz as Memórias Associativas Nebulosas Implicativas (IFAMs, Implicative Fuzzy Associative Memories) e suas versões duais com respeitoà negação e adjunção. Uma IFAMé uma FMAM onde os pares de entrada e saída são armazenados usando o armazenamento nebuloso implicativo. No armazenamento nebuloso implicativo, os pesos sinápticos são determinados computando o mínimo das implicações das ativações pré e pós-sinápticas. Resultados sobre a fase de armazenamento das IFAMs e das IFAMs duais são apresentados. Em particular, são demonstrados teoremas sobre a convergência, capacidade de armazenamento, tolerânciaà ruído e pontos fixos das IFAMs e das IFAMs duais para o caso autoassociativo. As IFAMs são comparadas com os principais modelos de FAMs por meio de exemplos e resultados teóricos. Finalmente, são apresentadas duas aplicações das FMAMs em problemas de previsão de séries temporais. O primeiro problema trata da previsão da mãode-obra requerida em indústrias metalúrgicas enquanto que a segunda aplicação refere-se a previsão da vazão média mensal da usina hidrelétrica de Furnas.

In researches that examine neuroplasticity, many studies that are performed directly on isolated neurons in the pyramidal cells of CA1 area (CA1) and slices of the hippocampus indicate that changes occur at the molecular and cellular levels during long-term synaptic potentiation (LTP), and these changes are dependent on N-methyl-D-aspartate (NMDA) acid receptors and/or purinergic receptors. Electrophysiological studies and the chemical induction of LTP of synaptic neurotransmissions provide key evidence that LTP is dependent on the volume of Ca 2+ influx through postsynaptic NMDA receptors, in addition to the subsequent activation and autophosphorylation of Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) and the increase in the density of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors on postsynaptic neuronal membranes. The primary peculiarity of LTP in the central nervous system (CNS) excitatory synapses is the synthesis of additional AMPA receptors in the postsynaptic elements. Furthermore, the proteolysis of the extracellular matrix (ECM) has an important role in the synaptic neuroplasticity of the CNS. Proteases from the serine family and metalloproteinases of the extracellular matrix are localized within the synapses and are released into the extracellular space in proportion to the degree of neuronal excitation. These enzymes cause changes in the morphology, shape and size, as well as the overall number of synapses and synthesize new synaptic connections. The proteinases also change the function of receptors, and consequently, the secretions of neurotransmitters from the presynaptic elements are strengthened or weakened.

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Microglia, the immune cells of the brain, are important for neurodevelopment and have been hypothesized to play a role in the pathogenesis of schizophrenia (SCZ). Although previous postmortem studies pointed toward presence of microglial activation, this view has been challenged by more recent hypothesis‐driven and hypothesis‐free analyses. The aim of the present study is to further understand the observed microglial changes in SCZ. We first performed a detailed meta‐analysis on studies that analyzed microglial cell density, microglial morphology, and expression of microglial‐specific markers. We then further explored findings from the temporal cortex by performing immunostainings and qPCRs on an additional dataset. A random effect meta‐analysis showed that the density of microglial cells was unaltered in SCZ (ES: 0.144 95% CI: 0.102 to 0.390, p = .250), and clear changes in microglial morphology were also absent. The expression of several microglial specific genes, such as CX3CR1, ...

Schizophrenia (SCZ) is a chronic neurodevelopmental psychotic disorder. The immune system and neuroinflammation seem to play a central role in the pathophysiology of SCZ. Clozapine is an effective atypical antipsychotic used for treatment-resistant SCZ. Life-threatening side effects, such as myocarditis, limit its use. We investigated the immunomodulatory effects of clozapine in an astroglial model of neuroinflammation. We thus assessed the effect of clozapine on the production of inflammatory mediators in human-derived astroglial (A172) cells, stimulated with a cytokine mix (TNFα, IL-1β, IFNγ). RT-PCR and ELISA analyses demonstrated that clozapine suppressed gene expression and production of TNFα, IL-1β and IL-8 and increased COX2 mRNA 24 h after stimulation. Clozapine inhibited Akt phosphorylation induced by the cytokine mix at 10 min and 40 min, as assessed by Western blot analysis with anti-pT308Akt antibody. Pretreatment with the Akt inhibitor MK-2206 increased COX2 gene expres...

Although acute promyelocytic leukemias (APLs) are consistently associated with a reciprocal chromosome 15;17 translocation, the gene(s) directly affected by the breakpoints have never been isolated. The chromosome 17 breakpoint maps to near the retinoic acid receptor alpha (RAR alpha) locus. Investigation of 20 APLs and a large series of other neoplastic patients and normal controls revealed RAR alpha gene rearrangements and aberrant transcripts only in the APL cases. These findings suggest that the RAR alpha gene is involved in the APL chromosome 17 breakpoint, is implicated in leukemogenesis, and could be used as a marker for identifying leukemic promyelocytes.

E strogens and phytoestrogen such as genistein, have been demonstrated to promote anti-oxidant and anti-inflammatory properties after Aβ cell death induction. We previously published that genistein can induced anti-inflammatory proteins such as PPAR-γ and decrease IL-1 and TNF-α (proinflammatory proteins) producing a decrease in apoptosis in astrocytes in primary culture. To know the molecular mechanism of action, we look for protein expression of MAPkinases, such as ERK, JUN and p-38 and also we determine NFkB and AP-1 protein induction in astrocytes in primary culture. Our data indicate that Aβ compound can trigger signal transduction pathways linked to apoptosis, such as caspases, p53, and bcl-2 genes. This programmed-cell death may be considered actually one of the important targets in a preventive approach against Alzheimer's disease. How estrogens and phytoestrogens do regulate and control the intracellular signaling cascades considered as relevant targets in neurodegenerative preventive approach remains to be elucidated. The results suggest that in neural cells, blocking the cellular signal transduction might trigger the induction of apoptosis and also estrogens can regulate signaling cascades to stop conversion of a normal cell to an affected one by compounds in Alzheimer's disease.

Neuroglia, including microglia and astrocytes, is a critical component of the central nervous system (CNS) that interacts with neurons to modulate brain activity, development, metabolism and signaling pathways. Thus, a better understanding of the role of neuroglia in the brain is critical. Complementing clinical and rodent data, the zebrafish (Danio rerio) is rapidly becoming an important model organism to probe the role of neuroglia in brain disorders. With high genetic and physiological similarity to humans and rodents, zebrafish possess some common (shared), as well as some specific molecular biomarkers and features of neuroglia development and functioning. Studying these common and zebrafish-specific aspects of neuroglia may generate important insights into key brain mechanisms, including neurodevelopmental, neurodegenerative, neuroregenerative and neurological processes. Here, we discuss the biology of neuroglia in humans, rodents and fish, its role in various CNS functions, and further directions of translational research into the role of neuroglia in CNS disorders using zebrafish models.

This paper concerns the application of two neural network architetures to solve the problem of visual interception of a stationary 3D target by a stereo (binocular) vision system. The neural networks are trained using competitive and unsupervised learning. The first neural architecture uses two Fuzzy-ART pattern-clustering neural networks which are combined with a linear "representation layer" to act as a fast open-loop neural controller and provides a rapid and coarse positioning of the visual system. The second neural architecture is a Kohonen network that acts as a closed-loop neural controller and provides a slower but more accurate positioning of the visual system. We show how to use these two neural architectures separately and combined to solve the visual interception problem. Simulation results of some interception tasks are presented and show that the better results are obtained when both neural architectures are combined.

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, except for brief excerpts in connection with reviews or scholarly analysis. Use in connection with any form of information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed is forbidden. The use in this publication of trade names, trademarks, service marks, and similar terms, even if they are not identified as such, is not to be taken as an expression of opinion as to whether or not they are subject to proprietary rights.

The extraction of electrophysiological features that reliably forecast the occurrence of seizures is one of the most challenging goals in epilepsy research. Among possible approaches to tackle this problem is the use of active probing paradigms in which responses to stimuli are used to detect underlying system changes leading up to seizures. This work evaluates the theoretical and mechanistic underpinnings of this strategy using two coupled populations of the well-studied Wendling neural mass model. Different model settings are evaluated, shifting parameters (excitability, slow inhibition, or inter-population coupling gains) from normal towards ictal states while probing stimuli are applied every 2 seconds to the input of either one or both populations. The correlation between the extracted features and the ictogenic parameter shifting indicates if the impending transition to the ictal state may be identified in advance. Results show that not only can the response to the probing sti...

Apresenta-se neste trabalho, um estudo da influência da perda de neurônios na taxa de disparos neuronais. Para tal estudo foi elaborado um modelo de autômato celular que simula a proliferação de células cancerígenas em um tecido cerebral e a morte de neurônios devido a falta de assistência das células que lhes dão suporte nutricional e funcional. Por meio do modelo analisou-se a taxa de disparos neuronais considerando diferentes valores de perturbação externa e probabilidades de proliferação de células cancerígenas. Com este trabalho conclui-se que a presença de proliferação não controlada de células, diminui a taxa de disparos neuronais.

In recent decades, there has been a growing interest in the impact of electric fields generated in the brain. Transmembrane ionic currents originate electric fields in the extracellular space and are capable of affecting nearby neurons, a phenomenon called ephaptic neuronal communication. In the present work, the Quadratic Integrated-and-Fire model (QIF-E) underwent an adjustment/improvement to include the ephaptic entrainment behavior between neurons and electric fields. Indeed, the aim of our study is to validate the QIF-E model, which is a model to estimate the influence of electric fields on neurons. For this purpose, we evaluated whether the main properties observed in an experiment by Anastassiou et al. (Nat Neurosci 14:217-223, 2011), which analyzed the effect of an electric field on cortical pyramidal neurons, are reproduced with the QIF-E model. In this way, the analysis tools are employed according to the neuronal activity regime: (i) for the subthreshold regime, the circular statistic is used to describe the phase differences between the input stimulus signal (electrode) and the modeled membrane response; (ii) in the suprathreshold regime, the Population Vector and the Spike Field Coherence are used to estimate phase preferences and the entrainment intensity between the input stimulus and Action Potentials. The results observed are (i) in the subthreshold regime the values of the phase differences change with distinct frequencies of the input stimulus; (ii) in the suprathreshold regime the preferential phase of Action Potentials changes for different frequencies. In addition, we explore other parameters of the model, such as noise and membrane characteristic-time, in order to understand different types of neurons and extracellular environment related to ephaptic communication. Such results are consistent with results observed in empirical experiments based on ephaptic phenomenon. In addition, the QIF-E model allows further studies on the physiological importance of ephaptic communication in the brain, and its simplicity may open a door to simulate the ephaptic response in neuronal networks and assess the impact of ephaptic communication in such scenarios.

The convergence of a multilayer perceptron toward a global minimum error in the backpropagation algorithm can be accelerated by introducing the representation of weight search space in accordance with the Riemann geometry, which consider curved spaces. The trajectory of the search vector at the training phase is modified by a "force" originated from the curvature of weight space. The main idea is inspired at the General Relativity theory, and the search space (now a manifold) must be controlled by parameters like spatial density and scale factor, modifying the gradient descent in the backpropagation algorithm.

Bellerophons ho ve trieJ ro put pa iJ to the monseer. N"eJham has chaliengeJ the validity of prevailing principles and modes of classification (1971 , 1975). Schneider has sought to sever the cu ltu ral constructs fmm a he rerogeneous social conglomera te (1968. 1972); while Inden has twea ked its metaphysical tail by pointing Qut thac oth er cultures may have quite Jifferenr assumptions about how humans are related (1 976). Yet the monster staggers on. largely I suspect because anth ropology is heir tn a strongly essentialist inrellec ru al tradition. U nl ess we are quite clear about what kind of C thin g' kinship is, we may flnJ we have bee n wast ing our rime calking about it. There are three gro unds on which I wis h to arglle that kinship does not have the kind of reality uSlially attributeJ to it. First. ,here is a ptoblem of (Tansla,ion and compari son. H ow Jo we know (h ar what we ca ll kin ship denmes somedling comparable in another c lll[Ure~ Second, chere is rh e ques rion of whac statemenrs abollt ki"ship are abollt. Are we deali ng wi th descriptions abo ut ,he world ! O r is it more a matter of what va ri ous classi fica tions of relationships may be used , for pa rticular purposes, to asse rt, claim , challenge Or J eny' Finally, [here is the metaphysical issue of what the members of different cultures recogni ze. ex plicitly or implicitly, as existing in their world. How does the classifica rion of relationships relate (0 what is held to exist! In other words, how are events, Mares and agents or whateve r unde rstood in Jj fferent cultura l theories of being, idenrity, nature, causa tion and so fonh ? I wo ulJ suggest th at using rhe notion of kinshi p, even as 'an odd-job word ', tends [Q cover up the difficulty in knowing how we translate; what uses of language may exi st; and wherher (h e entities classified by other cultures are remmely comparable. Our cultural heritage has yielded a pa rticular jural, moral and ontologica l pac kage we call kinship. It woulJ be a startling example of what someone once Jelightfully called 'RUP'-Residual Unresolved Positivism-were we co fail (0 see th at our ideas about kinship me no simpl e tr uths about the world but affected by our changing assumptions. I, is nOt an issue of how (0 compa re fac ts but of how, using one cogniti ve model, to talk about others. As the issues are complex, Ie< me spell Out some of the poi nts mos t relev ant to a discussion of ki ns hip. In its easiest formula tion the prob lem of raJica l translation (between unrelateJ languages where there has been little, or no, cultural contac t, see Q lIine 1960:28 R) is an extreme example of the hermeneu ti c issue of how t(.) interpret texts or sratemenrs wirhin one culture. For 'the speci al problem of inrerpret;Jri on is th at it very often ap/Jears to be necessary anJ ine vitabl e when in fac t it never is. T his appearance of inevimbi li ty is a phantas m raised by rhe circlilari[y of the interpretive process' (Hitsch 1967: 164). The reason is that one is dea ling wi,h a system of signs which 'must be consuueJ before jt furnishes connrmarion of an interpretarion. Furrhermore, the manner in which th e signs are construeJ is pardy predetermined by the interpretation itself' (Hi rsc h 1967: 165). In rad ica l translation rhe ethnographer Is Tltere Kinship in Bali! faces the trap of se l f~confirmabil ity of inrerpretations with metaphysica l knobs on.

CX3CR1, a G protein-coupled receptor solely expressed by microglia in the brain, has been repeatedly reported to be associated with neurodevelopmental disorders including schizophrenia (SCZ) and autism spectrum disorders (ASD) in transcriptomic and animal studies but not in genetic studies. To address the impacts of variants in CX3CR1 on neurodevelopmental disorders, we conducted coding exon-targeted resequencing of CX3CR1 in 370 Japanese SCZ and 192 ASD patients using next-generation sequencing technology, followed by a genetic association study in a sample comprising 7054 unrelated individuals (2653 SCZ, 574 ASD and 3827 controls). We then performed in silico three-dimensional (3D) structural modeling and in vivo disruption of Akt phosphorylation to determine the impact of the detected variant on CX3CR1-dependent signal transduction. We detected a statistically significant association between the variant Ala55Thr in CX3CR1 with SCZ and ASD phenotypes (odds ratio = 8.3, P = 0.020). A 3D structural model indicated that Ala55Thr could destabilize the conformation of the CX3CR1 helix 8 and affect its interaction with a heterotrimeric G protein. In vitro functional analysis showed that the CX3CR1-Ala55Thr mutation inhibited cell signaling induced by fractalkine, the ligand for CX3CR1. The combined data suggested that the variant Ala55Thr in CX3CR1 might result in the disruption of CX3CR1 signaling. Our results strengthen the association between microglia-specific genes and neurodevelopmental disorders.

Schizophrenia (SCZ) is a chronic neurodevelopmental psychotic disorder. The immune system and neuroinflammation seem to play a central role in the pathophysiology of SCZ. Clozapine is an effective atypical antipsychotic used for treatment-resistant SCZ. Life-threatening side effects, such as myocarditis, limit its use. We investigated the immunomodulatory effects of clozapine in an astroglial model of neuroinflammation. We thus assessed the effect of clozapine on the production of inflammatory mediators in human-derived astroglial (A172) cells, stimulated with a cytokine mix (TNFα, IL-1β, IFNγ). RT-PCR and ELISA analyses demonstrated that clozapine suppressed gene expression and production of TNFα, IL-1β and IL-8 and increased COX2 mRNA 24 h after stimulation. Clozapine inhibited Akt phosphorylation induced by the cytokine mix at 10 min and 40 min, as assessed by Western blot analysis with anti-pT308Akt antibody. Pretreatment with the Akt inhibitor MK-2206 increased COX2 gene expres...

In an e.m. study of the relations between nervous, muscular and glio-interstitial cells of Glossodoris (Gastropoda), the following types of association have been observed :
1 - neuro-neural connections, mainly axo-axonic synapses in the ganglionic neuropil and in peripheral nerves
2 - neuro-muscular connections, observed in the foot, the rhinophore and in the gut, apparently the typical neuro-effector junctions
3 - neuro-interstitial cell connections, similar to the neuro-muscular type, suggesting that the interstitial cell itself may be an effector
4 -  glio-glial connections between glial processes in the central nervous system
5 - interstitio-muscular connections, which are numerous and intimate, although often with a basement membrane interposed
Evidence for extrusion of granules from the interstitial cell surface may indicate a diffuse secretory activity of this special cell type
A model representing the possible interactions among nervous, muscular and glio-interstitial elements is proposed.

A limiting membrane is always present, although sometimes broken (see, for example, broken membranes in "ensheating cells" described by 2s.-Nagy and S.-Rozsa, 1970), perhaps as a result of fixation artifacts, but when the limiting lu h h TABLE Il TELOGLIA Group Genus and species Organ Name given to glia Granules Reference Gastropods Prosobranchs Littorina littorea Cephalic Nmemnd@ngen Newosekretoriscben Storch and Welsch (1969) tentacle Elementaqramla Pulmonates Lymnaea stagnalis Heart Ensheathing cells Membrane-bounded areas 2s.-Nagy and S.-Rozsa (1970) of granulated material Helix pomatia Penis retractor Glaa~ellen muscle GIiagram Schlote (1963) Helix pomatia, Hindgut Companion cells Large granular bodies Campbell and Burnstock Helix aspersa, Optic tentacle Sheath cells Dense granules Rogers (1968) Helix asperfa Foot Peripheral glial cells Dglse inclusions Rogers (1969a) Helix aspersa Epineural sheath Supporting cells Large, dense granules Rogers (1969b) Arcbatbatifla H a s t Sheath cells Granules Baxter and Nisbet (1963) Poneroplax afbida (1968) L i m a Jaws