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1.
Neuroscience Bulletin ; (6): 1-13, 2023.
Article in English | WPRIM | ID: wpr-971533

ABSTRACT

Differing from other subtypes of inhibitory interneuron, chandelier or axo-axonic cells form depolarizing GABAergic synapses exclusively onto the axon initial segment (AIS) of targeted pyramidal cells (PCs). However, the debate whether these AIS-GABAergic inputs produce excitation or inhibition in neuronal processing is not resolved. Using realistic NEURON modeling and electrophysiological recording of cortical layer-5 PCs, we quantitatively demonstrate that the onset-timing of AIS-GABAergic input, relative to dendritic excitatory glutamatergic inputs, determines its bi-directional regulation of the efficacy of synaptic integration and spike generation in a PC. More specifically, AIS-GABAergic inputs promote the boosting effect of voltage-activated Na+ channels on summed synaptic excitation when they precede glutamatergic inputs by >15 ms, while for nearly concurrent excitatory inputs, they primarily produce a shunting inhibition at the AIS. Thus, our findings offer an integrative mechanism by which AIS-targeting interneurons exert sophisticated regulation of the input-output function in targeted PCs.


Subject(s)
Axon Initial Segment , Axons/physiology , Neurons , Synapses/physiology , Pyramidal Cells/physiology , Interneurons/physiology , Action Potentials/physiology
2.
Neuroscience Bulletin ; (6): 1050-1068, 2023.
Article in English | WPRIM | ID: wpr-982460

ABSTRACT

The axon initial segment (AIS) is a highly specialized axonal compartment where the action potential is initiated. The heterogeneity of AISs has been suggested to occur between interneurons and pyramidal neurons (PyNs), which likely contributes to their unique spiking properties. However, whether the various characteristics of AISs can be linked to specific PyN subtypes remains unknown. Here, we report that in the prelimbic cortex (PL) of the mouse, two types of PyNs with axon projections either to the contralateral PL or to the ipsilateral basal lateral amygdala, possess distinct AIS properties reflected by morphology, ion channel expression, action potential initiation, and axo-axonic synaptic inputs from chandelier cells. Furthermore, projection-specific AIS diversity is more prominent in the superficial layer than in the deep layer. Thus, our study reveals the cortical layer- and axon projection-specific heterogeneity of PyN AISs, which may endow the spiking of various PyN types with exquisite modulation.


Subject(s)
Mice , Animals , Axon Initial Segment , Synapses/physiology , Pyramidal Cells/physiology , Cerebral Cortex , Axons/physiology
3.
Medicina (B.Aires) ; Medicina (B.Aires);79(1,supl.1): 27-32, abr. 2019. ilus, tab
Article in Spanish | LILACS | ID: biblio-1002601

ABSTRACT

Los trastornos del espectro autista (TEA) son una alteración funcional de la corteza cerebral, que presenta anomalías estructurales del neurodesarrollo que afectan fundamentalmente a la función sináptica y el patrón de conexiones dentro y entre columnas corticales. Desde su aspecto etiológico, el TEA tiene una importante carga genética, considerándose un desorden derivado de una combinación de mutaciones "de novo", asociadas a una predisposición derivada de variaciones comunes heredadas. Las principales anomalías genéticas asociadas a TEA implican genes que codifican proteínas de la sinapsis. Así, en pacientes con TEA se han descrito alteraciones del desarrollo inicial de las sinapsis en los circuitos de conexión entre áreas corticales de procesamiento complejo. La complejidad molecular observada en la predisposición a desarrollar un TEA, junto con la diversidad de fenotipos estructurales neuronales, ha hecho que los modelos animales reproduzcan solo parcialmente el TEA. Para avanzar en el estudio experimental se hace pues necesario desarrollar modelos más representativos, como son los modelos celulares derivados de células humanas. En las últimas décadas, el desarrollo de la biología de las células madre nos da medios para acceder a paradigmas experimentales sobre células derivadas de individuos con TEA. Actualmente, los modelos de células plutipotentes inducidas (IPs) derivadas de células humanas permiten profundizar en el estudio de las bases moleculares y celulares del TEA. Sin embargo, presentan problemas inherentes derivados de la manipulación experimental que conlleva la reprogramación de la expresión génica, por lo que otros modelos celulares se están también postulando como válidos.


Autism Spectrum Disorders (ASD) are a functional alteration of the cerebral cortex, which presents structural neurodevelopmental anomalies that affect synaptic function and the pattern of connections within and between cortical columns. From its etiological aspect, ASD has an important genetic load, considering a polygenic disorder, derived from a combination of "de novo" genetic mutations, associated to a predisposition derived from common inherited variations. The main genetic anomalies associated with ASD involve genes that encode proteins of the synapse. Thus, in patients with ASD, alterations in the initial development of the synapses have been described in the connection circuits between complex processing cortical areas. The molecular complexity observed in the predisposition to develop an ASD, together with the diversity of structural phenotypes, has made animal models reproduce only partially the ASD. To advance in the experimental study it is therefore necessary to develop representative models, such as cellular models derived from human cells. In recent decades, the advances in stem cell biology give us a way to apply experimental paradigms in cells derived from individuals with ASD. Currently, induced pluripotent cells (IPs) derived from human adult cells allow deepening the study of molecular and cellular bases of the neuronal development in humans, as well as the anomalies in this development, which give rise to disorders such as ASD. However, they present inherent problems derived from the experimental manipulation that involves the reprogramming of gene expression, therefore other models are also been explored.


Subject(s)
Humans , Autism Spectrum Disorder/physiopathology , Models, Biological , Synapses/physiology , Synapses/genetics , Gene Expression , Genetic Predisposition to Disease/genetics , Epigenesis, Genetic/genetics , Induced Pluripotent Stem Cells/cytology , Neurodevelopmental Disorders/physiopathology , Autism Spectrum Disorder/genetics
4.
Rev. chil. neuropsicol. (En línea) ; 13(1): 1-5, ago. 2018.
Article in Spanish | LILACS | ID: biblio-1099481

ABSTRACT

El objetivo de esta revisión es dar a conocer las diferentes vertientes que sustentan el proceso del aprendizaje en base a un concepto que ha alcanzado una gran importancia en los últimos años, el Ambiente Enriquecido (AE). Un término que ha sido emanado desde la biología, con diversos estudios de laboratorio realizados por científicos de renombre mundial y que, progresivamente ha ido incorporándose a disciplinas como la Psicología y la Pedagogía. En este artículo proponemos la descripción del impacto de este concepto en el proceso de aprendizaje experimentado por los seres humanos y su abordaje desde una perspectiva multidisciplinaria. Comenzamos por describir las bases neurofisiológicas del aprendizaje, con los fundamentos de la teoría neuronal como principal protagonista, pasando por la importancia de la Plasticidad Sináptica (PS) en el proceso de aprendizaje, el fenómeno de la Potenciación a Largo Plazo (PLP), como proceso generador de redes neuronales efectivas y sólidas. Posteriormente abordamos la génesis del Ambiente Enriquecido, con su origen en los experimentos con ratones de laboratorio, para posteriormente describir los conceptos y términos que han emanado del mismo que han sido aplicables a la Psicología Educacional tales como el Ambiente Desafiante, los instrumentos necesarios para su implementación y también el importante rol de las emociones en el proceso de aprendizaje de los sujetos. Finalmente, describimos el rol de la Pedagogía en la aplicación de actividades efectivas que conduzcan a un aprendizaje significativo en base al Ambiente Enriquecido.


The aim of this review is to present different strands that sustain the learning process based on a concept that has reached a major importance in recent years, the Enriched Environment (EE). A term that has been emerged from biology, with various laboratory studies conducted by world-renowned scientists and that has progressively been incorporated into disciplines such as Psychology and Education. In this article, we propose the description of the impact of this concept on the learning process experienced by human beings and its approach from a multidisciplinary perspective. We begin by describing the neurophysiological bases of learning, with the fundamentals of neuronal theory as the main protagonist, passing through the importance of Synaptic Plasticity (SP) in the learning process, the phenomenon of Long Term Potentiation (LTP), as a generating process of effective and solid neural networks. Subsequently, we covered the genesis of the Enriched Environment, with its origin in the experiments with laboratory mice, to later describe the concepts and terms that have emanated from it and have been applicable to Educational Psychology, such as Challenging Environment, the necessary instruments for its implementation and the important role of emotions in the subjects' learning process. Finally, we describe the role of Education in the implementation of effective activities that lead to meaningful learning based on the Enriched Environment.


Subject(s)
Humans , Environment , Learning/physiology , Neuronal Plasticity/physiology , Synapses/physiology
5.
Biol. Res ; 51: 35, 2018. graf
Article in English | LILACS | ID: biblio-983939

ABSTRACT

BACKGROUND: The previous studies have demonstrated the reduction of thiamine diphosphate is specific to Alzheimer's disease (AD) and causal factor of brain glucose hypometabolism, which is considered as a neurodegenerative index of AD and closely correlates with the degree of cognitive impairment. The reduction of thiamine diphosphate may contribute to the dysfunction of synapses and neural circuits, finally leading to cognitive decline. RESULTS: To demonstrate this hypothesis, we established abnormalities in the glucose metabolism utilizing thiamine deficiency in vitro and in vivo, and we found dramatically reduced dendrite spine density. We further detected lowered excitatory neurotransmission and impaired hippocampal long-term potentiation, which are induced by TPK RNAi in vitro. Importantly, via treatment with benfotiamine, Aß induced spines density decrease was considerably ameliorated. CONCLUSIONS: These results revealed that thiamine deficiency contributed to synaptic dysfunction which strongly related to AD pathogenesis. Our results provide new insights into pathogenesis of synaptic and neuronal dysfunction in AD.


Subject(s)
Animals , Male , Synapses/physiology , Thiamine Deficiency/complications , Thiamine Deficiency/metabolism , Thiamine Pyrophosphate/deficiency , Alzheimer Disease/etiology , Alzheimer Disease/metabolism , Neurons/physiology , Thiamine Deficiency/physiopathology , Thiamine Pyrophosphate/metabolism , Random Allocation , Blotting, Western , Amyloid beta-Peptides/metabolism , Rats, Sprague-Dawley , Diphosphotransferases/metabolism , Synaptic Transmission/physiology , Dendritic Spines/metabolism , Alzheimer Disease/physiopathology , Real-Time Polymerase Chain Reaction , Glucose/metabolism , Hippocampus/physiopathology , Hippocampus/metabolism , Mice, Inbred C57BL
6.
Braz. dent. j ; Braz. dent. j;25(5): 409-415, Sep-Oct/2014. tab, graf
Article in English | LILACS | ID: lil-731057

ABSTRACT

Chemical solutions play important roles in endodontic treatment and promote ultrastructural changes in dentin surface. The aim of this study was to quantify root canal roughness at different concentrations of calcium hypochlorite (Ca(OCl)2) and sodium hypochlorite (NaOCl) by confocal laser scanning microscopy (CLSM). Fifty-two human mandibular premolars were sectioned and randomly organized into thirteen groups (n=8): saline (control); 1%, 2.5% and 5% NaOCl; 1%, 2.5% and 5% Ca(OCl)2; the hypochlorite groups were further divided into with or without EDTA. The chlorine concentrations of the different solutions were measured by iodine titration (%). The superficial roughness (Sa) was quantified by CLSM. Ca(OCl)2 presented substantial decrease in chlorine concentration that differed from the package indication, but without compromising the dentin ultrastructure changes. There were no significant differences in dentin roughness between Ca(OCl)2 or NaOCl at all studied concentrations. The combination with EDTA provided similar roughness values among the solutions (p>0.05). The 5% Ca(OCl)2 and NaOCl solutions significantly increased dentin roughness and did not differ from the EDTA association (p>0.05). Ca(OCl)2 promoted similar dentin roughness as the NaOCl at the same concentrations and combined with EDTA. It may be concluded that Ca(OCl)2 modified the root canal dentin roughness similarly to NaOCl, at the same concentrations and EDTA combinations used in this study. Ca(OCl)2 and NaOCl, both at 5%, significantly altered dentin roughness, overcoming EDTA association, thus Ca(OCl)2 concentrations ranging from 1% to 2.5% may be suitable solutions for root canal irrigation protocols.


Soluções químicas são fundamentais para o tratamento endodôntico; entretanto, promovem alterações ultraestruturais na superfície dentinária. O objetivo deste estudo foi quantificar a rugosidade da dentina radicular com diferentes concentrações de hipoclorito de cálcio (Ca(OCl)2) e hipoclorito de sódio (NaOCl) utilizando microscopia confocal à laser (CLSM). Foram utilizados 52 premolares humanos inferiores e aleatoriamente divididos em treze grupos (n=8): Soro fisiológico (controle); NaOCl a 1%, 2,5% and 5%; Ca(OCl)2 a 1%, 2,5% and 5%; os grupos de hipoclorito foram subdivididos pela associação ou não ao ácido etilenodiaminotetracético (EDTA). A concentração de cloro ativo foi avaliada para diferentes soluções utilizando titulação iodométrica (%). A rugosidade superficial (Sa) foi quantificada por CLSM. Ca(OCl)2 apresentou perda substancial de cloro ativo e que foi distinta da condição descrita pelo fabricante, sem entretanto comprometer as alterações no substrato dentinário. Não houve diferenças significantes na rugosidade dentinária produzida pelos Ca(OCl)2 e NaOCl em todas as concentrações estudadas e associação com EDTA. A associação ao EDTA produziu rugosidade semelhante entre as soluções (p>0.05). O Ca(OCl)2 e NaOCl na concentração de 5% aumentaram significativamente a rugosidade dentinária e não apresentaram diferenças dos valores obtidos com a associação de EDTA (p>0.05). O Ca(OCl)2 alterou a rugosidade da dentina radicular de forma semelhante ao NaOCl, nas concentrações e associações utilizadas neste estudo. Como a concentração de 5% de Ca(OCl)2 e NaOCl, apresentou maior rugosidade dentinária, independente da associação ao EDTA, pode-se concluir que Ca(OCl)2 nas concentrações de 1% e 2,5% pode ser considerado uma solução adequada para a irrigação de canais radiculares.


Subject(s)
Animals , Rats , Calcium/metabolism , Hippocampus/physiology , Pyramidal Cells/physiology , Synapses/physiology , Differential Threshold , Electric Stimulation , Hippocampus/cytology , In Vitro Techniques , Rats, Sprague-Dawley
7.
Salud pública Méx ; 56(4): 393-401, jul.-ago. 2014. ilus
Article in Spanish | LILACS | ID: lil-733305

ABSTRACT

Objetivo. Examinar la investigación hecha en México sobre los determinantes sociales de la salud (DSS) durante el periodo 2005-2012 con base en la caracterización del sistema nacional de investigación en salud y la producción científica sobre este tema. Material y métodos. Análisis en dos etapas: revisión documental de fuentes oficiales sobre investigación en salud en México y búsqueda sistemática de literatura sobre DSS. Resultados. Los DSS fueron mencionados en el Programa de Acción Específico de Investigación en Salud 2007-2012, pero no figuran en las estrategias y objetivos; en su lugar, se enfatizan primordialmente aspectos de infraestructura y administrativos. En el periodo se publicaron 145 artículos sobre DSS, cuyas temáticas más abordadas fueron "condiciones de salud", "sistemas de salud" y "nutrición y obesidad". Conclusiones. A pesar de que existe investigación en México sobre DSS, la instrumentación de esos hallazgos en políticas de salud no se ha implementado. El Programa Sectorial de Salud 2013-2018 representa una ventana de oportunidad para posicionar resultados de investigación que promuevan políticas de equidad en salud.


Objective. To examine the research on social determinants of health (SDH) produced in Mexico during the period 2005-2012, based on the characterization of the national health research system and the scientific production on this topic. Materials and methods. Two-stage analyses: Review of Mexican documents and official sources on health research and systematic bibliographic review of the literature on SDH. Results. Although SDH were mentioned in the Specific Action Plan for Health Research 2007-2012, they are not implemented in strategies and goals, as the emphasis is put mostly in infrastructure and administrative aspects of research. In the period studied, 145 articles were published on SDH topics such as health conditions, health systems and nutrition and obesity. Conclusions. In spite of the availability of research on SDH in Mexico, the operationalization of such findings into health policies has not been possible. The current Sectorial Program on Health 2013-2018 represents a window of opportunity to position research findings that promote health equity policies.


Subject(s)
Animals , Drosophila Proteins , Drosophila/physiology , Gene Expression Regulation, Developmental , Genes, Tumor Suppressor , Insect Hormones/genetics , Neuromuscular Junction/physiology , Synapses/physiology , Synapses/ultrastructure , Tumor Suppressor Proteins , Axons , Drosophila/genetics , Evoked Potentials , Genes, Insect , Insect Hormones/biosynthesis , Microscopy, Electron , Motor Neurons/physiology , Motor Neurons/ultrastructure , Muscles/innervation , Mutagenesis , Neuromuscular Junction/ultrastructure , Synaptic Transmission
8.
Acta cir. bras ; Acta cir. bras;28(11): 774-777, Nov. 2013.
Article in English | LILACS | ID: lil-695957

ABSTRACT

PURPOSE: To assess the probable actions of ropivacaine, 50% enantiomeric excess bupivacaine mixture (S75-R25) and levobupivacaine on neuromuscular transmission in vitro. METHODS: Thirty rats were distributed into groups (n=5) according to the drug used: ropivacaine, bupivacaine (S75-R25) and levobupivacaine. The concentration used for the three local anesthetics (LA) was 5 µg.mL.-1The following parameters were evaluated: 1) LA effects on membrane potential (MP) and miniature end plate potential (MEPP). A chick biventer cervicis preparation was also used to evaluate LA effects on the contracture response to acetylcholine. RESULTS: LA did not alter MP values and decreased the frequency and amplitude of MEPP. In a chick biventer cervicis preparation, bupivacaine (S75-R25) and levobupivacaine decreased the contracture response to acetylcholine with statistical significance, in comparison to ropivacaine. CONCLUSIONS: In the concentrations used, levobupivacaine and bupivacaine (S75-R25) exhibited presynaptic and postsynaptic actions evidenced by alterations in miniature end plate potentials and contracture response to acetylcholine. Ropivacaine only had a presynaptic action.


Subject(s)
Animals , Male , Rats , Amides/pharmacology , Anesthetics, Local/pharmacology , Bupivacaine/analogs & derivatives , Bupivacaine/pharmacology , Synapses/drug effects , Synaptic Transmission/drug effects , Acetylcholine/administration & dosage , Acetylcholine/pharmacology , Amides/administration & dosage , Anesthetics, Local/administration & dosage , Bupivacaine/administration & dosage , Membrane Potentials/drug effects , Rats, Wistar , Synapses/physiology , Synaptic Transmission/physiology
9.
Braz. J. Psychiatry (São Paulo, 1999, Impr.) ; Braz. J. Psychiatry (São Paulo, 1999, Impr.);35(2): 173-177, April-June 2013.
Article in English | LILACS | ID: lil-680893

ABSTRACT

We review recent work on three major lines of memory research: a) the possible role of the protein kinase M-zeta (PKMzeta) in memory persistence; b) the processes of “synaptic tagging and capture” in memory formation; c) the modulation of extinction learning, widely used in the psychotherapy of fear memories under the name of “exposure therapy”. PKMzeta is a form of protein kinase C (PKC) that apparently remains stimulated for months after the consolidation of a given memory. Synaptic tagging is a mechanism whereby the weak activation of one synapse can tag it with a protein so other synapses in the same cell can reactivate it by producing other proteins that bind to the tag. Extinction, once mistakenly labeled as a form of forgetting, is by itself a form of learning; through it animals can learn to inhibit a response. We now know it can be modulated by neurotransmitters or by synaptic tagging, which should enable better control of its clinical use.


Subject(s)
Humans , Memory/physiology , Protein Kinase C/physiology , Synapses/physiology , Enzyme Activation/physiology , Extinction, Psychological/physiology , Hippocampus/physiology , Long-Term Potentiation/physiology
11.
Rev. bras. pesqui. méd. biol ; Braz. j. med. biol. res;45(12): 1221-1233, Dec. 2012. ilus, tab
Article in English | LILACS | ID: lil-659633

ABSTRACT

The cortical layer 1 contains mainly small interneurons, which have traditionally been classified according to their axonal morphology. The dendritic morphology of these cells, however, has received little attention and remains ill defined. Very little is known about how the dendritic morphology and spatial distribution of these cells may relate to functional neuronal properties. We used biocytin labeling and whole cell patch clamp recordings, associated with digital reconstruction and quantitative morphological analysis, to assess correlations between dendritic morphology, spatial distribution and membrane properties of rat layer 1 neurons. A total of 106 cells were recorded, labeled and subjected to morphological analysis. Based on the quantitative patterns of their dendritic arbor, cells were divided into four major morphotypes: horizontal, radial, ascendant, and descendant cells. Descendant cells exhibited a highly distinct spatial distribution in relation to other morphotypes, suggesting that they may have a distinct function in these cortical circuits. A significant difference was also found in the distribution of firing patterns between each morphotype and between the neuronal populations of each sublayer. Passive membrane properties were, however, statistically homogeneous among all subgroups. We speculate that the differences observed in active membrane properties might be related to differences in the synaptic input of specific types of afferent fibers and to differences in the computational roles of each morphotype in layer 1 circuits. Our findings provide new insights into dendritic morphology and neuronal spatial distribution in layer 1 circuits, indicating that variations in these properties may be correlated with distinct physiological functions.


Subject(s)
Animals , Rats , Action Potentials/physiology , Cell Size , Interneurons/cytology , Neurons/cytology , Neurons/physiology , Synaptic Transmission/physiology , Dendrites/physiology , Neural Pathways/cytology , Neural Pathways/physiology , Synapses/physiology
12.
Rev. bras. pesqui. méd. biol ; Braz. j. med. biol. res;44(10): 1054-1059, Oct. 2011. ilus
Article in English | LILACS | ID: lil-600698

ABSTRACT

Epilepsy is a neurological disorder associated with excitatory and inhibitory imbalance within the underlying neural network. This study evaluated inhibitory γ-amino-butyric acid (GABA)ergic modulation in the CA1 region of the hippocampus of male Wistar rats and Wistar audiogenic rats (aged 90 ± 3 days), a strain of inbred animals susceptible to audiogenic seizures. Field excitatory postsynaptic potentials and population spike complexes in response to Schaffer collateral fiber stimulation were recorded in hippocampal slices before and during application of picrotoxin (50 µM, 60 min), a GABA A antagonist, and the size of the population spike was quantified by measuring its amplitude and slope. In control audiogenic-resistant Wistar rats (N = 9), picrotoxin significantly increased both the amplitude of the population spike by 51 ± 19 percent and its maximum slope by 73 ± 21 percent. In contrast, in slices from Wistar audiogenic rats (N = 6), picrotoxin caused no statistically significant change in population spike amplitude (33 ± 46 percent) or slope (11 ± 29 percent). Data are reported as means ± SEM. This result indicates a functional reduction of GABAergic neurotransmission in hippocampal slices from Wistar audiogenic rats.


Subject(s)
Animals , Male , Rats , CA1 Region, Hippocampal/drug effects , Epilepsy/metabolism , GABA Antagonists/pharmacology , Picrotoxin/pharmacology , Synaptic Transmission/drug effects , gamma-Aminobutyric Acid/metabolism , CA1 Region, Hippocampal/metabolism , Neural Inhibition/drug effects , Neural Inhibition/physiology , Rats, Wistar , Synapses/drug effects , Synapses/physiology
13.
J Indian Med Assoc ; 2007 Sep; 105(9): 513-4, 516-8, 520-1
Article in English | IMSEAR | ID: sea-105446

ABSTRACT

Neuroplasticity is the phenomenon in brain where different stimuli lead to increase or decrease in the number of brain cells and remodelling of synapses. Neuroplasticity research has now established beyond doubt that instead being a static cell mass, our brain is actually a dynamic system of neural network that has the capability of significant growth under favourable circumstances. This obviously opens up new possibilities in treatment of disorders where neural loss or synaptic decay is major factor in molecular aetiopathogeneis. Neuroplasticity research unravels the way stress acts. Similarly it gives new hypothesis regarding depression and epilepsy. Novel therapeutic approaches based on neuroplastic findings are also discussed.


Subject(s)
Adaptation, Physiological , Depression/physiopathology , Epilepsy/physiopathology , Humans , Neuronal Plasticity/physiology , Neurons/physiology , Neurosciences , Synapses/physiology
14.
J Biosci ; 2007 Jan; 32(1): 129-44
Article in English | IMSEAR | ID: sea-110767

ABSTRACT

Complex processes resulting from interaction of multiple elements can rarely be understood by analytical scientific approaches alone; additional, mathematical models of system dynamics are required. This insight, which disciplines like physics have embraced for a long time already, is gradually gaining importance in the study of cognitive processes by functional neuroimaging. In this field, causal mechanisms in neural systems are described in terms of effective connectivity. Recently, dynamic causal modelling (DCM) was introduced as a generic method to estimate effective connectivity from neuroimaging data in a Bayesian fashion. One of the key advantages of DCM over previous methods is that it distinguishes between neural state equations and modality-specific forward models that translate neural activity into a measured signal. Another strength is its natural relation to Bayesian model selection (BMS) procedures. In this article, we review the conceptual and mathematical basis of DCM and its implementation for functional magnetic resonance imaging data and event-related potentials. After introducing the application of BMS in the context of DCM, we conclude with an outlook to future extensions of DCM. These extensions are guided by the long-term goal of using dynamic system models for pharmacological and clinical applications, particularly with regard to synaptic plasticity.


Subject(s)
Animals , Bayes Theorem , Brain/anatomy & histology , Humans , Magnetic Resonance Imaging , Models, Neurological , Synapses/physiology
15.
Indian J Pediatr ; 2005 Oct; 72(10): 855-7
Article in English | IMSEAR | ID: sea-79775

ABSTRACT

Research in the field of neurosciences and genetics has given us great insight into the understanding of learning and behavior and changes in the brain in response to experience. It is seen that brain is dynamically changing throughout life and is capable of learning at any time. Critical periods of neuroplasticity for various streams of development are also better understood. Technological advances in non invasive imaging techniques and advances in molecular genetics have helped us understand the basis of many developmental disorders which may help in planning effective intervention strategies.


Subject(s)
Adult , Age Factors , Brain Mapping , Child , Coffin-Lowry Syndrome/diagnosis , Critical Period, Psychological , Developmental Disabilities/diagnosis , Electroencephalography , Female , Fragile X Syndrome/diagnosis , Humans , Infant, Newborn , Long-Term Potentiation/physiology , Magnetic Resonance Imaging , Male , Molecular Biology , Neuronal Plasticity/physiology , Neurons/physiology , Neurophysiology , Neurosciences , Pregnancy , Research , Synapses/physiology , Time Factors
16.
Rev. bras. pesqui. méd. biol ; Braz. j. med. biol. res;38(1): 105-110, Jan. 2005. graf
Article in English | LILACS | ID: lil-405541

ABSTRACT

The nucleus tractus solitarius (NTS) plays an important role in the control of autonomic reflex functions. Glutamate, acting on N-methyl-D-aspartate (NMDA) and non-NMDA ionotropic receptors, is the major neurotransmitter in this nucleus, and the relative contribution of each receptor to signal transmission is unclear. We have examined NMDA excitatory postsynaptic currents (NMDA-EPSCs) in the subpostremal NTS using the whole cell patch clamp technique on a transverse brainstem slice preparation. The NMDA-EPSCs were evoked by stimulation of the solitary tract over a range of membrane potentials. The NMDA-EPSCs, isolated pharmacologically, presented the characteristic outward rectification and were completely blocked by 50 æM DL-2-amino-5-phosphonopentanoic acid. The I-V relationship of the NMDA response shows that current, with a mean (± SEM) amplitude of -41.2 ± 5.5 pA, is present even at a holding potential of -60 mV, suggesting that the NMDA receptors are weakly blocked by extracellular Mg2+ at near resting membrane potentials. This weak block can also be inferred from the value of 0.67 ± 0.17 for parameter delta obtained from a fit of the Woodhull equation to the I-V relationship. The maximal inward current measured on the I-V relationship was at -38.7 ± 4.2 mV. The decay phase of the NMDA currents was fitted with one exponential function with a decay time constant of 239 ± 51 and 418 ± 80 ms at a holding potential of -60 and +50 mV, respectively, which became slower with depolarization (e-fold per 145 mV). The biophysical properties of the NMDA receptors observed in the present study suggest that these receptors in the NTS contain NR2C subunits and may contribute to the synaptic signal integration.


Subject(s)
Animals , Male , Female , Rats , Neurons/chemistry , Receptors, N-Methyl-D-Aspartate/analysis , Solitary Nucleus/cytology , Synapses/physiology , Synaptic Transmission/physiology , Electrophysiology , Membrane Potentials/physiology , Neurons/physiology , Patch-Clamp Techniques , Rats, Wistar , Solitary Nucleus/physiology
17.
Article in English | WPRIM | ID: wpr-634810

ABSTRACT

The regulation of astroglia on synaptic plasticity in the CA1 region of rat hippocampus was examined. Rats were divided into three groups: the newly born (< 24 h), the juvenile (28-30 days) and the adult groups (90 - 100 days), with each group having 20 animals. The CA1 region of rat hippocampus was immunohistochemically and electron-microscopically examined, respectively, for the growth of astroglia and the ultrastructure of synapses. The high performance liquid chromatography was employed to determine the cholesterol content of rat hippocampus. In the newly-born rats, a large number of neurons were noted in the hippocampal CA1 region of the newly-born rats, and few astroglia and no synaptic structure were observed. In the juvenile group, a few astroglias and some immature synapses were found, which were less than those in adult rats (P < 0.01). The cholesterol content was 2.92 +/- 0.03 mg/g, 11.20 +/- 3.41 mg/g and 12.91 +/- 1.25 mg/g for newly born, the juvenile and the adult groups, respectively, with the differences among them being statistically significant (P < 0.01). Our study suggests that the astrocytes may play an important role in the synaptic formation and functional maturity of hippocampal neurons, which may be related to the secretion of cholesterol from astrocytes.


Subject(s)
Age Factors , Animals, Newborn , Astrocytes/cytology , Astrocytes/metabolism , Astrocytes/physiology , CA1 Region, Hippocampal/physiology , CA1 Region, Hippocampal/ultrastructure , Cell Communication/physiology , Cholesterol/metabolism , Neuronal Plasticity/physiology , Random Allocation , Rats, Wistar , Synapses/physiology , Synapses/ultrastructure
18.
J Biosci ; 2001 Jun; 26(2): 179-91
Article in English | IMSEAR | ID: sea-110953

ABSTRACT

Synaptophysin and syntaxin-1 are membrane proteins that associate with synaptic vesicles and presynaptic active zones at nerve endings, respectively. The former is known to be a good marker of synaptogenesis; this aspect, however, is not clear with syntaxin-1. In this study, the expression of both proteins was examined in the developing human retina and compared with their distribution in postnatal to adult retinas, by immunohistochemistry. In the inner plexiform layer, both were expressed simultaneously at 11-12 weeks of gestation, when synaptogenesis reportedly begins in the central retina. In the outer plexiform layer, however, the immunoreactivities were prominent by 16 weeks of gestation. Their expression in both plexiform layers followed a centre-to-periphery gradient. The immunoreactivities for both proteins were found in the immature photoreceptor, amacrine and ganglion cells; however, synaptophysin was differentially localized in bipolar cells and their axons, and syntaxin was present in some horizontal cells. In postnatal-to-adult retinas, synaptophysin immunoreactivity was prominent in photo-receptor terminals lying in the outer plexiform layer; on the contrary, syntaxin-1 was present in a thin immunoreactive band in this layer. In the inner plexiform layer, however, both were homogeneously distributed. Our study suggests that (i) syntaxin-1 appears in parallel with synapse formation; (ii) synaptogenesis in the human retina might follow a centre-to-periphery gradient; (iii) syntaxin-1 is likely to be absent from ribbon synapses of the outer plexiform layer, but may occur at presynaptic terminals of photoreceptor and horizontal cells, as is apparent from its localization in these cells, which is hitherto unreported for any vertebrate retina.


Subject(s)
Adult , Aging , Animals , Antigens, Surface/analysis , Embryo, Mammalian/chemistry , Fetus/chemistry , Gestational Age , Humans , Immunohistochemistry , Infant , Male , Nerve Tissue Proteins/analysis , Retina/chemistry , Synapses/physiology , Synaptophysin/analysis , Syntaxin 1
19.
Rev. chil. neuro-psiquiatr ; Rev. chil. neuro-psiquiatr;38(4): 221-7, oct.-dic. 2000. ilus
Article in Spanish | LILACS | ID: lil-282003

ABSTRACT

En el cerebro humano existen más de cien billones de celulas nerviosas.Están conectadas entre sí a través de una red de procesos nerviosos infinitamente compleja. El mensaje es transmitido desde una célula a otra a través de diferentes transmisores químicos. La transducción de la señal se produce en puntos de contacto especiales, llamados sinapsis. Una célula nerviosa puede tener cientos de tales contactos con otras células nerviosas. Los tres premios Nobel laureados en Fisiología o Medicina han efectuado descubrimientos pioneros sobre un tipo de transducción de señales entre células nerviosas, conocido como transducción sináptica lenta. Estos descubrimientos han sido cruciales para la comprensión del funcionamiento normal del cerebro y para entender cómo los transtornos de esa transducción de señal pueden dar lugar a enfermedades neurológicas y psiquiátricas. Esos hallazgos han posiblitado el desarrollo de nuevos fármacos


Subject(s)
Humans , Signal Transduction/physiology , Synaptic Transmission/physiology , Dopamine/metabolism , Learning/physiology , Memory/physiology , Neuronal Plasticity/physiology , Parkinson Disease/drug therapy , Phosphorylation , Synapses/physiology
20.
Arch. neurociencias ; Arch. neurociencias;1(3): 178-81, jul.-sept. 1996. ilus
Article in Spanish | LILACS | ID: lil-210812

ABSTRACT

El efecto de un nuevo anticonvulsionantem la 3-hidroxi, 3-etil, 3-fenil propionamida (HEPP) sobre las propiedades eléctricas de neuronas CA3 de hipocampo de rata, se estudió en rebanadas por medio de microelectrodos. Cuando se aplicaron pulsos de corriente depolarizante, la respuesta de las neuronas fueron de dos tipos. En un grupo de neuronas, la respuesta consistió en un número variable de potencias de acción cuya frecuencia aumentó al incrementar la intensidad de la corriente mientras que el otro grupo respondió con una ráfaga (burst) de potenciales de acción al inicio del pulso seguida de una biperpolarización de amplitud variable. En presencia de 50 M de HEPP, ocurrió un aumento reversible en la resistencia de entrada de la célula y del umbral del potencial de acción. No se conocen todavía los mecanismos iónicos para esta respuesta


Subject(s)
Rats , Animals , Anticonvulsants/pharmacokinetics , Hippocampus/drug effects , Microelectrodes/statistics & numerical data , Neurons/drug effects , Propionates/pharmacokinetics , Rats, Wistar/surgery , Synapses/physiology
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