Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 86.148
Filtrar
1.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 176-179, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33017958

RESUMO

How to utilize and interpret microscopic motor unit (MU) activities after surface electromyogram (sEMG) decomposition towards accurate decoding of the neural control remains a great challenge. In this study, a novel framework of hybrid encoder-decoder deep networks is proposed to process the microscopic neural drive information and it is applied to precise muscle force estimation. After a high-density sEMG (HD-sEMG) decomposition was performed using the progressive FastICA peel-off algorithm, a muscle twitch force model was then applied to basically convert each channel's electric waveform (i.e., action potential) of each MU into a twitch force. Next, hybrid encoder-decoder deep networks were performed on every 50 ms of segment of the summation of twitch force trains from all decomposed MUs. The encoder network was designed to characterize spatial information of MU's force contribution over all channels, and the decoder network finally decoded the muscle force. This framework was validated on HD-sEMG recordings from the abductor pollicis brevis muscles of five subjects by a thumb abduction task using an 8 × 8 grid. The proposed framework yielded a mean root mean square error of 6.62% ± 1.26% and a mean coefficient of determination value of 0.95 ± 0.03 from a linear regression analysis between the estimated force and actual force over all data trials, and it outperformed three common methods with statistical significance (p < 0.001). This study offers a valuable solution for interpreting microscopic neural drive information and demonstrates its success in predicting muscle force.


Assuntos
Algoritmos , Músculo Esquelético , Potenciais de Ação , Sistemas Computacionais , Eletromiografia
2.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 880-883, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018125

RESUMO

Parkinson's disease (PD) is characterized by excessively synchronized neural activity. In this paper, we recorded electrophysiological signals in Cortex of normal and PD mode monkey using homemade implantable microelectrode arrays (MEA), and analyzed the characteristics of action potentials (APs) and local field potentials (LFPs). Results showed that, comparing to normal monkey, the spike-firing activity of PD mode monkey could be divided into two stages: the continuous spike-firing stage and the burst spike-firing stage. The continuous spike-firing lasted for about 20s and oscillated at low frequency about 0.03Hz. APs fired in a burst mode between two continuous discharges. In the continuous spike-firing stage, the spike-firing activity was related to the ripple rhythm (100-200Hz) of LFPs with a coherence 0.86, while, in the burst spike-firing stage, it was related to the phase of theta rhythm (4-7 Hz). APs tended to discharge in the valley of theta rhythm (average peak phase is -10°).Clinical Relevance- This article can provide some references for the study of PD neuropathology.


Assuntos
Doença de Parkinson , Potenciais de Ação , Animais , Córtex Cerebral , Haplorrinos , Microeletrodos
3.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 894-897, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018128

RESUMO

In this paper, a method for the detection and subsequently extraction of neural spikes in an intra-cortically recorded neural signal is proposed. This method distinguishes spikes from the background noise based on the natural difference between their time-domain amplitude variation patterns. According to this difference, a spike mask is generated, which takes on large values over the course of spikes, and much smaller values for the background noise. The "high" part of this mask is designed to be wide enough to contain a complete spike. By multiplying the input neural signal with the spike mask, spikes are amplified with a large factor while the background noise is not. The result is a spike-augmented signal with significantly larger signal-to-noise ratio, on which spike detection is performed much more easily and accurately. According to this detection mechanism, spikes of the original neural signal are extracted.Clinical Relevance-This paper presents an automatic spike detection technique, dedicated to brain-implantable neural recording devices. Such devices are developed for clinical applications such as the treatment of epilepsy, neuro-prostheses, and brain-machine interfacing for therapeutic purposes.


Assuntos
Interfaces Cérebro-Computador , Processamento de Sinais Assistido por Computador , Potenciais de Ação , Algoritmos , Razão Sinal-Ruído
4.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 2315-2318, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018471

RESUMO

Dialysis is prescribed to renal failure patients as a long-term chronic treatment. Whereas dialysis therapeutically normalizes serum electrolytes and removes small toxin molecules, it fails to alleviate fibroblast induced structural fibrosis, and unresponsive uremia. The simultaneous presence of altered electrolytes and fibrosis or uremia is thought to be pro-arrhythmogenic. This study explored potential arrhythmogenesis under pre-dialysis (high electrolyte levels) and post-dialysis (low physiological electrolyte levels) in the presence of fibrosis and uremia in human atrial and ventricular model cardiomyocytes.Two validated human cardiomyocyte models were used in this study that permitted simulation of cardiac atrial and ventricular detailed electrophysiology. Pathological conditions simulating active fibrosis and uremia were implemented in both models. Pre- and post-dialysis conditions were simulated using high and low electrolyte levels respectively. Arrythmogenesis was quantified by computing restitution curves that permitted identification of action potential duration and calcium transient alternans instabilities.In comparison to control conditions, fibrosis abbreviated action potential durations while uremia prolonged the same. Under pre-dialysis conditions, an elevation of serum electrolyte levels caused action potential durations to be abbreviated under both fibrosis and uremia. Alternans instability was observed in the ventricular cardiomyocyte model. Under post-dialysis conditions, lower levels of serum electrolytes promoted an abbreviated action potential duration under fibrosis but caused a large increase of the control and uremic action potential durations. Alternans instabilities were observed in the atrial cardiomyocyte model under post-dialysis conditions at physiological heart rates. The calcium transient restitution showed similar alternans instabilities.Co-existing conditions such as fibrosis and uremia in the presence of unphysiological electrolyte levels promote arrhythmogenesis and may require additional treatment to improve dialysis outcomes.Clinical Relevance. Knowledge of model response to clinically relevant conditions permits use of in silico modeling to better understand and dissect underlying arrhythmia mechanisms.


Assuntos
Fibrilação Atrial , Miócitos Cardíacos , Potenciais de Ação , Átrios do Coração , Ventrículos do Coração , Humanos
5.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 2487-2490, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018511

RESUMO

Cardiac cellular models are utilized as the building blocks for tissue simulation. One of the imprecisions of conventional cellular modeling, especially when the models are used in tissue-level modeling, stems from the mere consideration of cellular properties (e.g., action potential shape) in parameter tuning of the model. In our previous work, we put forward an accurate framework in which membrane resistance (Rm) reflecting inter-cellular characteristics, i.e., electrotonic effects, was considered alongside cellular features in cellular model fitting. This paper, for the first time, examines the hypothesis that considering Rm as an additional optimization objective improves the accuracy of tissue-level modeling. To study this hypothesis, after cellular-level optimization of a well-known model, source-sink mismatch configurations in a 2-dimensional model are investigated. The results demonstrate that including Rm in the optimization protocol yields a substantial improvement in the relative error of the critical transition border which is defined as the minimum window size between source and sink that wave propagates. Model developers can utilize the proposed concept during parameter tuning to increase the accuracy of models.


Assuntos
Objetivos , Potenciais de Ação , Membranas
6.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 2585-2588, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018535

RESUMO

Increase in transmural dispersion of repolarisation along with a diminished QT interval have been known to aid in the development of arrhythmia during KCNQ1-linked short QT syndrome type 2 (SQTS2). However, the percentage by which action potential duration (APD) shortens in the different cell types that make up the ventricular wall are not fully understood. In this study, the percentage of APD shortening of M-cells was varied to determine the conditions under which re-entry occurs during SQTS2. A 2D transmural section of the heart with anisotropic properties is considered. Slight modifications to the TP06 equations are used to simulate the electrophysiology of the endocardial (endo), midmyocardial (M) and epicardial (epi) cells. A discrete network of 250×100 cells are interconnected using gap junction conductances and from this, a pseudo ECG is generated. On pacing the tissue with premature beats in the midst of normal pacing pulses and on including SQTS, it is observed that re-entry is sustained for a longer duration when the APD shortening in M-cells is more compared to the epi or endo cells while the percentage reduction in APD of M-cells is about 5% to 7% lesser than that in epi and endo cells. Further, when the percentage reduction in APD of M-cells is similar to epi or endo cells, no re-entry is generated. This analysis highlights the key role of percentage reduction in APD of M-cells compared to epi and endo cells in maintaining the re-entrant waves.


Assuntos
Arritmias Cardíacas , Sistema de Condução Cardíaco , Potenciais de Ação , Coração , Humanos
7.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 3078-3081, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018655

RESUMO

Brain-machine interfaces (BMIs) translate neural signals into digital commands to control external devices. During the use of BMI, neurons may change their activity corresponding to the same stimuli or movement. The changes are represented by the neural tuning parameters which may change gradually and abruptly. Adaptive algorithms were proposed to estimate the time-varying parameters in order to keep decoding performance stable. The existing methods only searched new parameters locally which failed to detect the abrupt changes. Global search helps but requires the known boundary of estimated parameter which is hard to be defined in many cases. We propose to estimate the neural modulation parameter by the global search using adaptive point process estimation. This neural modulation parameter represents the similarity between the kinematics and the neural preferred hyper tuning direction with finite range [0,1]. The preferred hyper tuning direction is then decoupled from the neural modulation parameter by gradient descent method. We apply the proposed method on real data to detect the abrupt change of the neural tuning parameter when the subject switched from manual control to brain control mode. The proposed method demonstrates better tracking on the neural hyper tuning parameters than local searching method and validated by KS statistical test.


Assuntos
Interfaces Cérebro-Computador , Potenciais de Ação , Algoritmos , Movimento , Neurônios
8.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 3236-3239, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018694

RESUMO

Identification of causal relationships of neural activity is one of the most important problems in neuroscience and neural engineering. We show that a novel deep learning approach using a convolutional neural network to model output neural spike activity from input neural spike activity is able to achieve high correlation between the predicted probability of spiking in the output neuron and the true probability of spiking in the output neuron for data generated with a generalized linear model. The convolutional neural network is also able to recover the true model variables (kernels) used to generate the probability of spiking in the output neuron. Based on the convolutional neural network model's validation via a generalized linear model, future work will include validation with non-linear models that use higher-order kernels.


Assuntos
Redes Neurais de Computação , Neurônios , Potenciais de Ação , Modelos Lineares , Probabilidade
9.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 3465-3468, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018749

RESUMO

We analyze the efficiency of motor unit (MU) filter prelearning from high-density surface electromyographic (HDEMG) recordings of voluntary muscle contractions in the identification of the motor unit firing patterns during elicited muscle contractions. Motor unit filters are assessed from 10 s long low level isometric voluntary contractions by gradient-based optimization of three different cost functions and then applied to synthetic HDEMG recordings of elicited muscle contractions with dispersion of motor unit firings ranging from 13 ms to 1 ms. We demonstrate that the number of identified MUs and the precision of MU identification depend significantly on the selected cost function. Regardless the selected cost function and MU synchronization level, the median precision of motor unit identification in elicited contraction is ≥ 95 % and is comparable to the precision in voluntary contractions. On the other hand, median miss rate increases significantly from < 1 % to ~ 3 % with the tested level of MU synchronization.Clinical Relevance-The identification of MU firings from HDEMG in elicited muscle contractions provides a new tool for in vivo investigation of motor excitability in humans.


Assuntos
Contração Isométrica , Neurônios Motores , Potenciais de Ação , Eletromiografia , Humanos , Contração Muscular
10.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 3477-3480, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018752

RESUMO

New methods for the analysis of electrically-evoked compound action potentials (eCAPs) are described. Mammalian nerves tend to have broad multi-modal distributions of fibre diameters, which translates into a spread of conduction velocities. The method of velocity selective recording (VSR) is unable to distinguish between this spectral spread and the transfer function of the system. The concept of the velocity impulse function (VIF) is introduced as a tool to differentiate between these signal and system attributes. The new methods enable separate estimates of velocity spectral broadening and signal-to-noise ratio (SNR) to be obtained.


Assuntos
Potenciais Evocados , Potenciais de Ação , Animais
11.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 3529-3532, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018765

RESUMO

Retinal microprostheses strive to evoke a sense of vision in individuals blinded by outer retinal degenerative diseases, by electrically stimulating the surviving retina. It is widely suspected that a stimulation strategy that can selectively activate different retinal ganglion cell types will improve the quality of evoked phosphenes. Previous efforts towards this goal demonstrated the potential for selective ON and OFF brisk-transient cell activation using high-rate (2000 pulses per second, PPS) stimulation. Here, we build upon this earlier work by testing an additional rate of stimulation and additional cell populations. We find considerable variability in responses both within and across individual cell types, but show that the sensitivity of a ganglion cell to repetitive stimulation is highly correlated to its single-pulse threshold. Consistent with this, we found thresholds for both stimuli to be correlated to soma size, and thus likely mediated by the properties of the axon initial segment. The ultimate efficacy of high-rate stimulation will likely depend on several factors, chief among which are (a) the residual ganglion types, and (b) the stimulation frequency.


Assuntos
Degeneração Retiniana , Células Ganglionares da Retina , Potenciais de Ação , Estimulação Elétrica , Humanos , Retina
12.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 3533-3536, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018766

RESUMO

Microelectronic retinal prostheses electrically stimulate retinal neurons with the goal of restoring vision in patients blinded by outer retinal degeneration. Despite some success in clinical trials, the quality of vision elicited by these devices is still limited. To improve the performance of retinal prostheses, our group studied how retinal neurons respond to electric stimulation. Our previous work showed that responses of retinal ganglion cells (RGCs) are frequency-dependent and different types of RGCs can be preferentially activated with a specific frequency and current amplitude. In the present study, we systemically examined responses of RGCs to sinusoidal electric stimulation with varying frequencies and amplitudes. We found that ON sustained alpha RGCs show distinct stimulus-response relationships to low and high frequency stimulation. For example, RGCs showed monotonic response curves to 500 Hz sinusoidal stimulation, whereas they showed non-monotonic response curves to 2000 Hz stimulation. We also described how increasing stimulus frequency gradually changed the response curves of RGCs.


Assuntos
Degeneração Retiniana , Próteses Visuais , Potenciais de Ação , Estimulação Elétrica , Humanos , Células Ganglionares da Retina
13.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 3819-3822, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018833

RESUMO

Different neural signal blocking technologies provide potential therapy for various diseases caused by pathological or involuntary neural activities. In this paper, a novel neural signal blocking concept based on spike-trapping principle is introduced. The blocking system was designed and implemented. In the system, a compound action potential was induced by a proximal stimulus, and a blocking signal was generated after a neural signal was detected, which was applied to the distal end of the nerve to block the nerve conduction. The reliability of the system was verified on bullfrog sciatic nerve gastrocnemius muscle specimens. The optimal blocking signal parameters, the relationship between nerve diameter and blocking threshold voltage, and the nerve safety of blocking signals were explored. The experimental results show that the system is possible to block a pathological or involuntary neural signal automatically. The average voltage of block threshold and the minimum pulse width are -1.66 V and 120 ms, respectively. The blocking threshold decreases as the diameter of the nerve increases. The blocking signals at the threshold level are safe for the stimulated nerve.


Assuntos
Bloqueio Nervoso , Nervo Isquiático , Potenciais de Ação , Animais , Condução Nervosa , Reprodutibilidade dos Testes
14.
PLoS Comput Biol ; 16(9): e1008198, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32931495

RESUMO

Calcium imaging with fluorescent protein sensors is widely used to record activity in neuronal populations. The transform between neural activity and calcium-related fluorescence involves nonlinearities and low-pass filtering, but the effects of the transformation on analyses of neural populations are not well understood. We compared neuronal spikes and fluorescence in matched neural populations in behaving mice. We report multiple discrepancies between analyses performed on the two types of data, including changes in single-neuron selectivity and population decoding. These were only partially resolved by spike inference algorithms applied to fluorescence. To model the relation between spiking and fluorescence we simultaneously recorded spikes and fluorescence from individual neurons. Using these recordings we developed a model transforming spike trains to synthetic-imaging data. The model recapitulated the differences in analyses. Our analysis highlights challenges in relating electrophysiology and imaging data, and suggests forward modeling as an effective way to understand differences between these data.


Assuntos
Cálcio/metabolismo , Fenômenos Eletrofisiológicos/fisiologia , Modelos Neurológicos , Imagem Molecular/métodos , Neurônios , Potenciais de Ação/fisiologia , Animais , Lobo Frontal/citologia , Lobo Frontal/fisiologia , Camundongos , Neurônios/metabolismo , Neurônios/fisiologia , Imagem Óptica
15.
PLoS Comput Biol ; 16(9): e1008165, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32941457

RESUMO

Combining information from multiple sources is a fundamental operation performed by networks of neurons in the brain, whose general principles are still largely unknown. Experimental evidence suggests that combination of inputs in cortex relies on nonlinear summation. Such nonlinearities are thought to be fundamental to perform complex computations. However, these non-linearities are inconsistent with the balanced-state model, one of the most popular models of cortical dynamics, which predicts networks have a linear response. This linearity is obtained in the limit of very large recurrent coupling strength. We investigate the stationary response of networks of spiking neurons as a function of coupling strength. We show that, while a linear transfer function emerges at strong coupling, nonlinearities are prominent at finite coupling, both at response onset and close to saturation. We derive a general framework to classify nonlinear responses in these networks and discuss which of them can be captured by rate models. This framework could help to understand the diversity of non-linearities observed in cortical networks.


Assuntos
Potenciais de Ação/fisiologia , Modelos Neurológicos , Rede Nervosa/citologia , Rede Nervosa/fisiologia , Neurônios/fisiologia , Animais , Encéfalo/citologia , Encéfalo/fisiologia , Biologia Computacional , Haplorrinos , Camundongos , Dinâmica não Linear
16.
Nat Commun ; 11(1): 4550, 2020 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-32917862

RESUMO

Place cells exhibit spatially selective firing fields that collectively map the continuum of positions in environments; how such activity pattern develops with experience is largely unknown. Here, we record putative granule cells (GCs) and mossy cells (MCs) from the dentate gyrus (DG) over 27 days as mice repetitively run through a sequence of objects fixed onto a treadmill belt. We observe a progressive transformation of GC spatial representations, from a sparse encoding of object locations and spatial patterns to increasingly more single, evenly dispersed place fields, while MCs show little transformation and preferentially encode object locations. A competitive learning model of the DG reproduces GC transformations via the progressive integration of landmark-vector cells and spatial inputs and requires MC-mediated feedforward inhibition to evenly distribute GC representations, suggesting that GCs slowly encode conjunctions of objects and spatial information via competitive learning, while MCs help homogenize GC spatial representations.


Assuntos
Fibras Musgosas Hipocampais/fisiologia , Células de Lugar/fisiologia , Aprendizagem Espacial/fisiologia , Potenciais de Ação/fisiologia , Animais , Eletrodos Implantados , Eletroencefalografia/instrumentação , Masculino , Camundongos , Modelos Animais , Técnicas Estereotáxicas/instrumentação
17.
PLoS Biol ; 18(8): e3000820, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32866173

RESUMO

Mutations in the gene encoding the microtubule-severing protein spastin (spastic paraplegia 4 [SPG4]) cause hereditary spastic paraplegia (HSP), associated with neurodegeneration, spasticity, and motor impairment. Complicated forms (complicated HSP [cHSP]) further include cognitive deficits and dementia; however, the etiology and dysfunctional mechanisms of cHSP have remained unknown. Here, we report specific working and associative memory deficits upon spastin depletion in mice. Loss of spastin-mediated severing leads to reduced synapse numbers, accompanied by lower miniature excitatory postsynaptic current (mEPSC) frequencies. At the subcellular level, mutant neurons are characterized by longer microtubules with increased tubulin polyglutamylation levels. Notably, these conditions reduce kinesin-microtubule binding, impair the processivity of kinesin family protein (KIF) 5, and reduce the delivery of presynaptic vesicles and postsynaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. Rescue experiments confirm the specificity of these results by showing that wild-type spastin, but not the severing-deficient and disease-associated K388R mutant, normalizes the effects at the synaptic, microtubule, and transport levels. In addition, short hairpin RNA (shRNA)-mediated reduction of tubulin polyglutamylation on spastin knockout background normalizes KIF5 transport deficits and attenuates the loss of excitatory synapses. Our data provide a mechanism that connects spastin dysfunction with the regulation of kinesin-mediated cargo transport, synapse integrity, and cognition.


Assuntos
Ácido Glutâmico/metabolismo , Cinesina/metabolismo , Transtornos da Memória/metabolismo , Transtornos da Memória/fisiopatologia , Memória de Curto Prazo , Neurônios/metabolismo , Espastina/deficiência , Tubulina (Proteína)/metabolismo , Potenciais de Ação , Animais , Membrana Celular/metabolismo , Espinhas Dendríticas/metabolismo , Espinhas Dendríticas/ultraestrutura , Potenciais Pós-Sinápticos Excitadores , Hipocampo/patologia , Hipocampo/fisiopatologia , Camundongos Knockout , Microtúbulos/metabolismo , Microtúbulos/ultraestrutura , Atividade Motora , Neurônios/patologia , Neurônios/ultraestrutura , Transporte Proteico , Espastina/metabolismo , Sinapses/metabolismo , Sinapses/ultraestrutura , Vesículas Sinápticas/metabolismo
18.
Nat Commun ; 11(1): 4395, 2020 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-32879322

RESUMO

The formation and maintenance of spatial representations within hippocampal cell assemblies is strongly dictated by patterns of inhibition from diverse interneuron populations. Although it is known that inhibitory synaptic strength is malleable, induction of long-term plasticity at distinct inhibitory synapses and its regulation of hippocampal network activity is not well understood. Here, we show that inhibitory synapses from parvalbumin and somatostatin expressing interneurons undergo long-term depression and potentiation respectively (PV-iLTD and SST-iLTP) during physiological activity patterns. Both forms of plasticity rely on T-type calcium channel activation to confer synapse specificity but otherwise employ distinct mechanisms. Since parvalbumin and somatostatin interneurons preferentially target perisomatic and distal dendritic regions respectively of CA1 pyramidal cells, PV-iLTD and SST-iLTP coordinate a reprioritisation of excitatory inputs from entorhinal cortex and CA3. Furthermore, circuit-level modelling reveals that PV-iLTD and SST-iLTP cooperate to stabilise place cells while facilitating representation of multiple unique environments within the hippocampal network.


Assuntos
Hipocampo/fisiologia , Interneurônios/metabolismo , Células Piramidais/fisiologia , Potenciais de Ação , Animais , Região CA1 Hipocampal/citologia , Região CA1 Hipocampal/fisiologia , Canais de Cálcio Tipo T/metabolismo , Channelrhodopsins/metabolismo , Hipocampo/citologia , Camundongos , Optogenética/métodos , Parvalbuminas/metabolismo , Técnicas de Patch-Clamp , Transdução de Sinais , Somatostatina/metabolismo , Sinapses/metabolismo
19.
Nat Commun ; 11(1): 4283, 2020 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-32883967

RESUMO

Our understanding of the spatiotemporal regulation of cardiogenesis is hindered by the difficulties in modeling this complex organ currently by in vitro models. Here we develop a method to generate heart organoids from mouse embryonic stem cell-derived embryoid bodies. Consecutive morphological changes proceed in a self-organizing manner in the presence of the laminin-entactin (LN/ET) complex and fibroblast growth factor 4 (FGF4), and the resulting in vitro heart organoid possesses atrium- and ventricle-like parts containing cardiac muscle, conducting tissues, smooth muscle and endothelial cells that exhibited myocardial contraction and action potentials. The heart organoids exhibit ultrastructural, histochemical and gene expression characteristics of considerable similarity to those of developmental hearts in vivo. Our results demonstrate that this method not only provides a biomimetic model of the developing heart-like structure with simplified differentiation protocol, but also represents a promising research tool with a broad range of applications, including drug testing.


Assuntos
Matriz Extracelular/metabolismo , Fator 4 de Crescimento de Fibroblastos/metabolismo , Coração , Células-Tronco Embrionárias Murinas/metabolismo , Organoides , Potenciais de Ação , Diamino Aminoácidos/metabolismo , Animais , Biomimética/métodos , Diferenciação Celular , Linhagem Celular , Células Endoteliais , Coração/crescimento & desenvolvimento , Coração/fisiologia , Glicoproteínas de Membrana/metabolismo , Camundongos , Contração Miocárdica , Miocárdio , Organoides/citologia , Organoides/crescimento & desenvolvimento , Organoides/ultraestrutura
20.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 49(4): 508-513, 2020 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-32985165

RESUMO

More and more evidences support that the abnormality of GABAergic interneurons is associated with autism spectrum disorders (ASD), epilepsy, schizophrenia and other neurodevelopmental disorders. In recent years, numerous drugs have been developed to regulate ion channels and receptors in GABAergic interneurons, including sodium channels and N-methyl-D-aspartate (NMDA) receptors. The activators of Na+ channel can enhance the action potential of GABAergic interneurons by reducing the inactivation of Na+ channel. NMDA receptor, as a potential therapeutic target of ASD, can restore the NMDA function of GABAergic interneurons, which would be used to treat behavioral defects. In addition, there are many ion channels and receptors on GABAergic interneurons related to ASD. This article reviews GABAergic interneurons in the pathogenesis of ASD and the related interventions.


Assuntos
Transtorno do Espectro Autista , Neurônios GABAérgicos , Interneurônios , Neurologia , Potenciais de Ação , Transtorno do Espectro Autista/fisiopatologia , Neurônios GABAérgicos/patologia , Humanos , Interneurônios/patologia , Neurologia/tendências , Receptores de N-Metil-D-Aspartato/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA