RESUMO
The critical brain hypothesis states that the brain can benefit from operating close to a second-order phase transition. While it has been shown that several computational aspects of sensory processing (e.g., sensitivity to input) can be optimal in this regime, it is still unclear whether these computational benefits of criticality can be leveraged by neural systems performing behaviorally relevant computations. To address this question, we investigate signatures of criticality in networks optimized to perform efficient coding. We consider a spike-coding network of leaky integrate-and-fire neurons with synaptic transmission delays. Previously, it was shown that the performance of such networks varies nonmonotonically with the noise amplitude. Interestingly, we find that in the vicinity of the optimal noise level for efficient coding, the network dynamics exhibit some signatures of criticality, namely, scale-free dynamics of the spiking and the presence of crackling noise relation. Our work suggests that two influential, and previously disparate theories of neural processing optimization (efficient coding and criticality) may be intimately related.
Assuntos
Potenciais de Ação , Modelos Neurológicos , Rede Nervosa , Neurônios , Transmissão Sináptica , Neurônios/fisiologia , Rede Nervosa/fisiologia , Transmissão Sináptica/fisiologia , Potenciais de Ação/fisiologia , Encéfalo/fisiologia , Humanos , AnimaisRESUMO
BACKGROUND: Primary electrical disorders (PEDs) are a group of cardiac rhythm abnormalities that occur in the absence of detectable structural heart disease and are a significant cause of sudden cardiac death (SCD). The initiation of cardiac muscle contraction and relaxation is orchestrated by the action potential (AP), generated through ionic changes across the membrane. Mutations in the AP-related gene CACNA2D1 have been identified as a causative factor for PED. METHODS: We recruited a Chinese family with a history of arrhythmia. The proband has experienced palpitations and chest tightness for over 40 years, with symptoms worsening over the past year. Whole exome sequencing (WES) was used to determine the genetic etiologies in this family. RESULTS: A novel heterozygous missense mutation (NM_000722.3: c.1685G > C;p.G562A) of CACNA2D1 gene was detected. Genotyping of the proband's parents indicated that the arrhythmia phenotype in the proband was caused by a de novo mutation. CONCLUSIONS: WES was utilized to explore the genetic etiology in a family with arrhythmia, leading to the identification of a novel mutation in the CACNA2D1 gene. This study not only expands the mutation spectrum of the CACNA2D1 gene but also contributes to genetic counseling and clinical diagnosis for this family.
Assuntos
Arritmias Cardíacas , Sequenciamento do Exoma , Predisposição Genética para Doença , Heterozigoto , Mutação de Sentido Incorreto , Linhagem , Fenótipo , Humanos , Masculino , Arritmias Cardíacas/genética , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/fisiopatologia , Feminino , China , Análise Mutacional de DNA , Adulto , Povo Asiático/genética , Canais de Cálcio/genética , Pessoa de Meia-Idade , Hereditariedade , Frequência Cardíaca/genética , Potenciais de Ação , População do Leste AsiáticoRESUMO
Cortical neurons exhibit temporally irregular spiking patterns and heterogeneous firing rates. These features arise in model circuits operating in a 'fluctuation-driven regime', in which fluctuations in membrane potentials emerge from the network dynamics. However, it is still debated whether the cortex operates in such a regime. We evaluated the fluctuation-driven hypothesis by analyzing spiking and sub-threshold membrane potentials of neurons in the frontal cortex of mice performing a decision-making task. We showed that while standard fluctuation-driven models successfully account for spiking statistics, they fall short in capturing the heterogeneity in sub-threshold activity. This limitation is an inevitable outcome of bombarding single-compartment neurons with a large number of pre-synaptic inputs, thereby clamping the voltage of all neurons to more or less the same average voltage. To address this, we effectively incorporated dendritic morphology into the standard models. Inclusion of dendritic morphology in the neuronal models increased neuronal selectivity and reduced error trials, suggesting a functional role for dendrites during decision-making. Our work suggests that, during decision-making, cortical neurons in high-order cortical areas operate in a fluctuation-driven regime.
Assuntos
Potenciais de Ação , Modelos Neurológicos , Neurônios , Animais , Neurônios/fisiologia , Camundongos , Potenciais de Ação/fisiologia , Córtex Cerebral/fisiologia , Córtex Cerebral/citologia , Tomada de Decisões/fisiologia , Potenciais da Membrana/fisiologia , Dendritos/fisiologia , Masculino , Camundongos Endogâmicos C57BL , Lobo Frontal/fisiologia , Lobo Frontal/citologiaRESUMO
OBJECTIVES: Hyperkalemia is a common life-threatening condition causing severe electrophysiologic derangements and arrhythmias. The beneficial effects of calcium (Ca 2+ ) treatment for hyperkalemia have been attributed to "membrane stabilization," by restoration of resting membrane potential (RMP). However, the underlying mechanisms remain poorly understood. Our objective was to investigate the mechanisms underlying adverse electrophysiologic effects of hyperkalemia and the therapeutic effects of Ca 2+ treatment. DESIGN: Controlled experimental trial. SETTING: Laboratory investigation. SUBJECTS: Canine myocytes and tissue preparations. INTERVENTIONS AND MEASUREMENTS: Optical action potentials and volume averaged electrocardiograms were recorded from the transmural wall of ventricular wedge preparations ( n = 7) at baseline (4 mM potassium), hyperkalemia (8-12 mM), and hyperkalemia + Ca 2+ (3.6 mM). Isolated myocytes were studied during hyperkalemia (8 mM) and after Ca 2+ treatment (6 mM) to determine cellular RMP. MAIN RESULTS: Hyperkalemia markedly slowed conduction velocity (CV, by 67% ± 7%; p < 0.001) and homogeneously shortened action potential duration (APD, by 20% ± 10%; p < 0.002). In all preparations, this resulted in QRS widening and the "sine wave" pattern observed in severe hyperkalemia. Ca 2+ treatment restored CV (increase by 44% ± 18%; p < 0.02), resulting in narrowing of the QRS and normalization of the electrocardiogram, but did not restore APD. RMP was significantly elevated by hyperkalemia; however, it was not restored with Ca 2+ treatment suggesting a mechanism unrelated to "membrane stabilization." In addition, the effect of Ca 2+ was attenuated during L-type Ca 2+ channel blockade, suggesting a mechanism related to Ca 2+ -dependent (rather than normally sodium-dependent) conduction. CONCLUSIONS: These data suggest that Ca 2+ treatment for hyperkalemia restores conduction through Ca 2+ -dependent propagation, rather than restoration of membrane potential or "membrane stabilization." Our findings provide a mechanistic rationale for Ca 2+ treatment when hyperkalemia produces abnormalities of conduction (i.e., QRS prolongation).
Assuntos
Cálcio , Hiperpotassemia , Hiperpotassemia/tratamento farmacológico , Animais , Cães , Cálcio/metabolismo , Potenciais de Ação/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Potenciais da Membrana/efeitos dos fármacos , Eletrocardiografia , Membrana Celular/efeitos dos fármacosRESUMO
Excitable cells such as neuronal and muscle cells can be primary targets in rapidly emerging electroporation-based treatments. However, they can be affected by electric pulses even in therapies where they are not the primary targets, and this can cause adverse side effects. Therefore, to optimize the electroporation-based treatments of excitable and non-excitable tissues, there is a need to study the effects of electric pulses on excitable cells, their ion channels, and excitability in vitro. For this purpose, a protocol was developed for optical monitoring of changes in action potential generation due to electroporation on a simple excitable cell model of genetically engineered tet-on spiking HEK cells. With the use of a fluorescent potentiometric dye, the changes in transmembrane voltage were monitored under a fluorescence microscope, and relevant parameters of cell responses were extracted automatically with a MATLAB application. This way, the excitable cell responses to different electric pulses and the interplay between excitation and electroporation could be efficiently evaluated.
Assuntos
Potenciais de Ação , Eletroporação , Eletroporação/métodos , Humanos , Células HEK293 , Potenciais de Ação/fisiologia , Engenharia Genética/métodos , Microscopia de Fluorescência/métodos , Corantes Fluorescentes/químicaRESUMO
BACKGROUND: Permanent left bundle branch area pacing (LBBAP) has been established as an effective means to correct left bundle branch block. Right bundle branch block (RBBB), emerge as a distinct form of cardiac conduction abnormality, can be seen in the context of LBBAP procedure. However, the correction potential of LBBAP in patients with RBBB remains largely unexplored. OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of permanent LBBAP in patients with RBBB. METHODS: Ninety-two consecutive patients who underwent successful permanent LBBAP were recruited from May. 2019 to Dec. 2022 in Fuwai Central China Cardiovascular Hospital. Among them, 20 patients with RBBB were included in our analysis. These patients were followed up at 1, 3, 6 and 12 months post-LBBAP. The QRS duration (QRSd) on the V1 lead of the 12-lead elctrocardiogram was measured and compared before and after the LBBAP procedure. Additionally, mitral regurgitation, tricuspid regurgitation and cardiac function were assessed using transthoracic echocardiography, specifically focusing on left ventricular ejection fraction (LVEF) and mitral regurgitation severity. The acute pitfills and delayed complications associated with the LBBAP procedure were recorded to evaluate its safety. SPSS 23.0 was used to perform statistical analysis with Student's t test or one way ANOVA or nonparametric tests (paired Wilcoxon test). A p value less than 0.05 was defined as significant. RESULTS: The demographic breakdown of the RBBB cohort revealed a mean age of 66.35 ± 11.55 years, 60% being male. Comorbidities were prevalent, including severe atrioventricular block (AVB) in 75%, sick sinus syndrome (SSS) in 20%, heart failure in 25%, atrial fibrillation in 30%, coronary heart diseases in 45%, hypertension in 35%, and diabetes mellitus in 15%. Regarding the LBBAP procedure, the average operation time was 106.53 ± 2.72 min, with 45% of patients (9 individuals) requiring temporary cardiac pacing during the surgery. Notably, the LBBAP procedure significantly narrow the QRS duration in RBBB patients, from 132.60 ± 31.49ms to 119.55 ± 18.58 ms (P = 0.046). Additionally, at the 12-month follow-up, we observed a marked improvement in LVEF, which increased significantly from 55.15 ± 10.84% to 58.5 ± 10.55% (P = 0.018). Furthermore, mitral regurgitation severity improved, with a median reduction from 4.46 (0.9, 7.3) to 2.29 (0, 3.49) cm2 (P = 0.033). Importantly, no cases of ventricular septum perforation or pericardial effusion were reported during the LBBAP procedure or during the follow-up period. CONCLUSION: LBBAP provides an immediate reduction in QRS duration for patients suffering from RBBB, accompanied by improvements in mitral regurgitation and cardiac function as evident in the 12-month follow-up period.
Assuntos
Fascículo Atrioventricular , Bloqueio de Ramo , Estimulação Cardíaca Artificial , Frequência Cardíaca , Insuficiência da Valva Mitral , Recuperação de Função Fisiológica , Volume Sistólico , Função Ventricular Esquerda , Humanos , Masculino , Feminino , Bloqueio de Ramo/fisiopatologia , Bloqueio de Ramo/diagnóstico , Bloqueio de Ramo/terapia , Insuficiência da Valva Mitral/fisiopatologia , Insuficiência da Valva Mitral/diagnóstico por imagem , Idoso , Resultado do Tratamento , Pessoa de Meia-Idade , Estimulação Cardíaca Artificial/efeitos adversos , Fatores de Tempo , Fascículo Atrioventricular/fisiopatologia , China , Potenciais de Ação , Estudos RetrospectivosRESUMO
Audiovisual (AV) interaction has been shown in many studies of auditory cortex. However, the underlying processes and circuits are unclear because few studies have used methods that delineate the timing and laminar distribution of net excitatory and inhibitory processes within areas, much less across cortical levels. This study examined laminar profiles of neuronal activity in auditory core (AC) and parabelt (PB) cortices recorded from macaques during active discrimination of conspecific faces and vocalizations. We found modulation of multi-unit activity (MUA) in response to isolated visual stimulation, characterized by a brief deep MUA spike, putatively in white matter, followed by mid-layer MUA suppression in core auditory cortex; the later suppressive event had clear current source density concomitants, while the earlier MUA spike did not. We observed a similar facilitation-suppression sequence in the PB, with later onset latency. In combined AV stimulation, there was moderate reduction of responses to sound during the visual-evoked MUA suppression interval in both AC and PB. These data suggest a common sequence of afferent spikes, followed by synaptic inhibition; however, differences in timing and laminar location may reflect distinct visual projections to AC and PB.
Assuntos
Córtex Auditivo , Estimulação Luminosa , Animais , Córtex Auditivo/fisiologia , Masculino , Estimulação Luminosa/métodos , Estimulação Acústica/métodos , Percepção Auditiva/fisiologia , Percepção Visual/fisiologia , Macaca mulatta , Potenciais de Ação/fisiologia , Neurônios/fisiologia , Feminino , Vocalização Animal/fisiologiaRESUMO
Packet information encoding of neural signals was proposed for vision about 50 years ago and has recently been revived as a plausible strategy generalizable to natural and artificial sensory systems. It involves discrete image segmentation controlled by feedback and the ability to store and compare packets of information. This article shows that neurons of the cerebellum-like electrosensory lobe (EL) of the electric fish Gymnotus omarorum use spike-count and spike-timing distribution as constitutive variables of packets of information that encode one-by-one the electrosensory images generated by a self-timed series of electric organ discharges (EODs). To evaluate this hypothesis, extracellular unitary activity was recorded from the centro-medial map of the EL. Units recorded in high-decerebrate preparations were classified into six types using hierarchical cluster analysis of post-EOD spiking histograms. Cross-correlation analysis indicated that each EOD strongly influences the unit firing probability within the next inter-EOD interval. Units of the same type were similarly located in the laminar organization of the EL and showed similar stimulus-specific changes in spike count and spike timing after the EOD when a metal object was moved close by, along the fish's body parallel to the skin, or when the longitudinal impedance of a static cylindrical probe placed at the center of the receptive field was incremented in a stepwise manner in repetitive trials. These last experiments showed that spike-counts and the relative entropy, expressing a comparative measure of information before and after the step, were systematically increased with respect to a control in all unit types. The post-EOD spike-timing probability distribution and the relatively independent contribution of spike-timing and number to the content of information in the transmitted packet suggest that these are the constitutive image-encoding variables of the packets. Comparative analysis suggests that packet information transmission is a general principle for processing superposition images in cerebellum-like networks.
Assuntos
Cerebelo , Animais , Cerebelo/fisiologia , Potenciais de Ação/fisiologia , Órgão Elétrico/fisiologia , Neurônios/fisiologia , Peixe Elétrico/fisiologia , Gimnotiformes/fisiologia , Rede Nervosa/fisiologiaRESUMO
Lesion studies have historically been instrumental for establishing causal connections between brain and behavior. They stand to provide additional insight if integrated with multielectrode techniques common in systems neuroscience. Here, we present and test a platform for creating electrolytic lesions through chronically implanted, intracortical multielectrode probes without compromising the ability to acquire neuroelectrophysiology. A custom-built current source provides stable current and allows for controlled, repeatable lesions in awake-behaving animals. Performance of this novel lesioning technique was validated using histology from ex vivo and in vivo testing, current and voltage traces from the device, and measurements of spiking activity before and after lesioning. This electrolytic lesioning method avoids disruptive procedures, provides millimeter precision over the extent and submillimeter precision over the location of the injury, and permits electrophysiological recording of single-unit activity from the remaining neuronal population after lesioning. This technique can be used in many areas of cortex, in several species, and theoretically with any multielectrode probe. The low-cost, external lesioning device can also easily be adopted into an existing electrophysiology recording setup. This technique is expected to enable future causal investigations of the recorded neuronal population's role in neuronal circuit function, while simultaneously providing new insight into local reorganization after neuron loss.
Over the past three decades, the field of neuroscience has made significant leaps in understanding how the brain works. This is largely thanks to microelectrode arrays, devices which are surgically implanted into the outermost layer of the brain known as the cortex. Once inserted, these devices can precisely monitor the electrical activity of a few hundred neurons while also stimulating neurons to reversibly modulate their activity. However, current microelectrode arrays are missing a key function: they cannot irreversibly inactivate neurons over long-time scales. This ability would allow researchers to understand how networks of neurons adapt and re-organize after injury or during neurodegenerative diseases where brain cells are progressively lost. To address this limitation, Bray, Clarke, et al. developed a device capable of creating consistent amounts of neuron loss, while retaining the crucial ability to record electrical activity following a lesion. Calibration tests in sheep and pigs provided the necessary parameters for this custom circuit, which was then verified as safe in non-human primates. These experiments demonstrated that the device could effectively cause neuron loss without compromising the recording capabilities of the microelectrode array. By seamlessly integrating neuron inactivation with monitoring of neuronal activity, scientists can now investigate the direct effects of such damage and subsequent neural reorganization. This device could help neuroscientists to explore neural repair and rehabilitation after brain cell loss, which may lead to better treatments for neurodegenerative diseases. In addition, this technique could offer insights into the interactions between neural circuits that drive behavior, enhancing our understanding of the complex mechanisms underlying how the brain works.
Assuntos
Neurônios , Animais , Neurônios/fisiologia , Eletrodos Implantados , Eletrólise/métodos , Ratos , Eletrofisiologia/métodos , Eletrofisiologia/instrumentação , Potenciais de Ação/fisiologiaRESUMO
Fixational eye movements alter the number and timing of spikes transmitted from the retina to the brain, but whether these changes enhance or degrade the retinal signal is unclear. To quantify this, we developed a Bayesian method for reconstructing natural images from the recorded spikes of hundreds of retinal ganglion cells (RGCs) in the macaque retina (male), combining a likelihood model for RGC light responses with the natural image prior implicitly embedded in an artificial neural network optimized for denoising. The method matched or surpassed the performance of previous reconstruction algorithms, and provides an interpretable framework for characterizing the retinal signal. Reconstructions were improved with artificial stimulus jitter that emulated fixational eye movements, even when the eye movement trajectory was assumed to be unknown and had to be inferred from retinal spikes. Reconstructions were degraded by small artificial perturbations of spike times, revealing more precise temporal encoding than suggested by previous studies. Finally, reconstructions were substantially degraded when derived from a model that ignored cell-to-cell interactions, indicating the importance of stimulus-evoked correlations. Thus, fixational eye movements enhance the precision of the retinal representation.
Assuntos
Movimentos Oculares , Fixação Ocular , Retina , Células Ganglionares da Retina , Animais , Células Ganglionares da Retina/fisiologia , Retina/fisiologia , Movimentos Oculares/fisiologia , Masculino , Fixação Ocular/fisiologia , Macaca mulatta , Teorema de Bayes , Algoritmos , Potenciais de Ação/fisiologia , Estimulação Luminosa , Modelos NeurológicosRESUMO
INTRODUCTION: Reliable, noninvasive early diagnostics of neuromuscular function in Bell's palsy, which causes facial paralysis and reduced quality of life, remain to be established. Here, we aimed to evaluate the utility of the motor unit number index (MUNIX) for the quantitative electrophysiological assessment of early-stage Bell's palsy, its correlation with clinical assessments, changes following treatment, and association with clinical prognosis. METHODS: MUNIX measures were recorded from the bilateral zygomaticus, orbicularis oculi, and orbicularis oris muscles of 10 healthy individuals and 64 patients with Bell's palsy. The patients were assessed by two specialist neurologists using the House-Brackmann and Sunnybrook Facial Grading Systems. Repeat assessments were performed on 20 patients with Bell's palsy who received treatment. Additionally, the 64 patients were reassessed using clinical scales after a 1-month interval. RESULTS: The MUNIX values of the main affected muscles on the affected side were lower than those on the healthy side in patients with Bell's palsy (p < .05). The MUNIX measurements significantly correlated with the clinical facial nerve palsy scale scores (p < .05). Significant improvements were observed in the MUNIX values on repeat testing following treatment (p < .05). The baseline motor unit size index (the compound muscle action potential amplitude divided by MUNIX) was positively associated with improved clinical presentation after 1 month (p < .05). CONCLUSION: MUNIX can be used as an electrophysiological biomarker for the quantitative assessment of facial nerve palsy and treatment response, and as a prognostic biomarker, in patients with early Bell's palsy, and is recommended as a complement to conventional neurophysiological examinations.
Assuntos
Paralisia de Bell , Eletromiografia , Humanos , Paralisia de Bell/fisiopatologia , Paralisia de Bell/diagnóstico , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Eletromiografia/métodos , Músculos Faciais/fisiopatologia , Adulto Jovem , Idoso , Biomarcadores , Neurônios Motores/fisiologia , Diagnóstico Precoce , Potenciais de Ação/fisiologiaRESUMO
Some visual neurons in the dragonfly (Hemicordulia tau) optic lobe respond to small, moving targets, likely underlying their fast pursuit of prey and conspecifics. In response to repetitive targets presented at short intervals, the spiking activity of these "small target motion detector" (STMD) neurons diminishes over time. Previous experiments limited this adaptation by including intertrial rest periods of varying durations. However, the characteristics of this effect have never been quantified. Here, using extracellular recording techniques lasting for several hours, we quantified both the spatial and temporal properties of STMD adaptation. We found that the time course of adaptation was variable across STMD units. In any one STMD, a repeated series led to more rapid adaptation, a minor accumulative effect more akin to habituation. Following an adapting stimulus, responses recovered quickly, though the rate of recovery decreased nonlinearly over time. We found that the region of adaptation is highly localized, with targets displaced by â¼2.5° eliciting a naive response. Higher frequencies of target stimulation converged to lower levels of sustained response activity. We determined that adaptation itself is a target-tuned property, not elicited by moving bars or luminance flicker. As STMD adaptation is a localized phenomenon, dependent on recent history, it is likely to play an important role in closed-loop behavior where a target is foveated in a localized region for extended periods of the pursuit duration.
Assuntos
Adaptação Fisiológica , Percepção de Movimento , Neurônios , Odonatos , Animais , Odonatos/fisiologia , Adaptação Fisiológica/fisiologia , Percepção de Movimento/fisiologia , Neurônios/fisiologia , Estimulação Luminosa/métodos , Potenciais de Ação/fisiologia , Lobo Óptico de Animais não Mamíferos/fisiologia , Feminino , MasculinoRESUMO
Dysfunction of the Nav1.5, Cav1.2, and Kv channels could interfere with the AP and result in arrhythmias and even heart failure. We herein present a novel library of nuciferine analogs that target ion channels for the treatment of arrhythmias. Patch clamp measurements of ventricular myocytes revealed that 6a dramatically blocked both the INa and ICa without altering the currentvoltage relationship (including the activation potential and peak potential), accelerated the inactivation of Nav and Cav channels and delayed the resurrection of these channels after inactivation. Additionally, 6a significantly decreased the APA and RMP without affecting the APD30 or APD50. The IC50 values of 6a against Nav1.5 and Cav1.2 were 4.98⯵M and 4.62⯵M, respectively. Furthermore, 6a (10⯵M) blocked IKs, IK1, and Ito with values of 17.01â¯%±2.54â¯%, 9.09â¯%±2.78â¯%, and 11.15â¯%±3.52â¯%, respectively. Surprisingly, 6a weakly inhibited hERG channels, suggesting a low risk of proarrhythmia. The cytotoxicity evaluation of 6a with the H9c2 cell line indicated that this compound was noncytotoxic. In vivo studies suggested that these novel nuciferine analogs could shorten the time of arrhythmia continuum induced by BaCl2 and normalize the HR, QRS, QT and QTc interval and the R wave amplitude. Moreover, 6a dose-dependently affected aconitine-induced arrhythmias and notably improved the cumulative dosage of aconitine required to evoke VP, VT, VF and CA in rats with aconitine-induced arrhythmia. In conclusion, nuciferine analogs could be promising ion channel blockers that could be further developed into antiarrhythmic agents.
Assuntos
Potenciais de Ação , Arritmias Cardíacas , Miócitos Cardíacos , Animais , Arritmias Cardíacas/tratamento farmacológico , Arritmias Cardíacas/induzido quimicamente , Potenciais de Ação/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Ratos , Ratos Sprague-Dawley , Masculino , Antiarrítmicos/farmacologia , Aporfinas/farmacologia , Humanos , Canais de Potássio de Abertura Dependente da Tensão da Membrana/antagonistas & inibidores , Canais de Potássio de Abertura Dependente da Tensão da Membrana/metabolismo , Canais de Potássio de Abertura Dependente da Tensão da Membrana/efeitos dos fármacos , Canais de Sódio Disparados por Voltagem/metabolismo , Canais de Sódio Disparados por Voltagem/efeitos dos fármacos , Bloqueadores do Canal de Sódio Disparado por Voltagem/farmacologia , Bloqueadores dos Canais de Potássio/farmacologia , Bloqueadores dos Canais de Cálcio/farmacologia , Técnicas de Patch-ClampRESUMO
Three major types of GABAergic interneurons, parvalbumin-, somatostatin-, and vasoactive intestinal peptide-expressing (PV, SOM, VIP) cells, play critical but distinct roles in the cortical microcircuitry. Their specific electrophysiology and connectivity shape their inhibitory functions. To study the network dynamics and signal processing specific to these cell types in the cerebral cortex, we developed a multi-layer model incorporating biologically realistic interneuron parameters from rodent somatosensory cortex. The model is fitted to in vivo data on cell-type-specific population firing rates. With a protocol of cell-type-specific stimulation, network responses when activating different neuron types are examined. The model reproduces the experimentally observed inhibitory effects of PV and SOM cells and disinhibitory effect of VIP cells on excitatory cells. We further create a version of the model incorporating cell-type-specific short-term synaptic plasticity (STP). While the ongoing activity with and without STP is similar, STP modulates the responses of Exc, SOM, and VIP cells to cell-type-specific stimulation, presumably by changing the dominant inhibitory pathways. With slight adjustments, the model also reproduces sensory responses of specific interneuron types recorded in vivo. Our model provides predictions on network dynamics involving cell-type-specific short-term plasticity and can serve to explore the computational roles of inhibitory interneurons in sensory functions.
Assuntos
Interneurônios , Modelos Neurológicos , Plasticidade Neuronal , Córtex Somatossensorial , Córtex Somatossensorial/fisiologia , Córtex Somatossensorial/citologia , Interneurônios/fisiologia , Plasticidade Neuronal/fisiologia , Animais , Peptídeo Intestinal Vasoativo/metabolismo , Potenciais de Ação/fisiologia , Parvalbuminas/metabolismo , Rede Nervosa/fisiologia , Somatostatina/metabolismo , RatosRESUMO
An important working hypothesis to investigate brain activity is whether it operates in a critical regime. Recently, maximum-entropy phenomenological models have emerged as an alternative way of identifying critical behavior in neuronal data sets. In the present paper, we investigate the signatures of criticality from a firing rate-based maximum-entropy approach on data sets generated by computational models, and we compare them to experimental results. We found that the maximum entropy approach consistently identifies critical behavior around the phase transition in models and rules out criticality in models without phase transition. The maximum-entropy-model results are compatible with results for cortical data from urethane-anesthetized rats data, providing further support for criticality in the brain.
Assuntos
Potenciais de Ação , Entropia , Modelos Neurológicos , Neurônios , Neurônios/fisiologia , Neurônios/citologia , Animais , RatosRESUMO
Continuous rate-based neural networks have been widely applied to modeling the dynamics of cortical circuits. However, cortical neurons in the brain exhibit irregular spiking activity with complex correlation structures that cannot be captured by mean firing rate alone. To close this gap, we consider a framework for modeling irregular spiking activity, called the moment neural network, which naturally generalizes rate models to second-order moments and can accurately capture the firing statistics of spiking neural networks. We propose an efficient numerical method that allows for rapid evaluation of moment mappings for neuronal activations without solving the underlying Fokker-Planck equation. This allows simulation of coupled interactions of mean firing rate and firing variability of large-scale neural circuits while retaining the advantage of analytical tractability of continuous rate models. We demonstrate how the moment neural network can explain a range of phenomena including diverse Fano factor in networks with quenched disorder and the emergence of irregular oscillatory dynamics in excitation-inhibition networks with delay.
Assuntos
Potenciais de Ação , Modelos Neurológicos , Rede Nervosa , Neurônios , Rede Nervosa/fisiologia , Neurônios/fisiologiaRESUMO
Spiking neural networks and neuromorphic hardware platforms that simulate neuronal dynamics are getting wide attention and are being applied to many relevant problems using Machine Learning. Despite a well-established mathematical foundation for neural dynamics, there exists numerous software and hardware solutions and stacks whose variability makes it difficult to reproduce findings. Here, we establish a common reference frame for computations in digital neuromorphic systems, titled Neuromorphic Intermediate Representation (NIR). NIR defines a set of computational and composable model primitives as hybrid systems combining continuous-time dynamics and discrete events. By abstracting away assumptions around discretization and hardware constraints, NIR faithfully captures the computational model, while bridging differences between the evaluated implementation and the underlying mathematical formalism. NIR supports an unprecedented number of neuromorphic systems, which we demonstrate by reproducing three spiking neural network models of different complexity across 7 neuromorphic simulators and 4 digital hardware platforms. NIR decouples the development of neuromorphic hardware and software, enabling interoperability between platforms and improving accessibility to multiple neuromorphic technologies. We believe that NIR is a key next step in brain-inspired hardware-software co-evolution, enabling research towards the implementation of energy efficient computational principles of nervous systems. NIR is available at neuroir.org.
Assuntos
Encéfalo , Modelos Neurológicos , Redes Neurais de Computação , Software , Encéfalo/fisiologia , Humanos , Neurônios/fisiologia , Simulação por Computador , Aprendizado de Máquina , Potenciais de Ação/fisiologiaRESUMO
Objective: To investigate the action potential firing patterns of neurons in the visual sensory layers of the superior colliculus in early postnatal mice and the electrophysiological characteristics of neurons with different firing patterns. Methods: This experimental study utilized whole-cell patch-clamp recordings performed on neurons in the visual sensory layers of the superior colliculus using brain slices from 57 healthy male C57BL/6J mice aged 14 to 20 days (weighing 5.0 to 8.9 g) using brain slices. In current-clamp mode, action potential characteristics were analyzed based on the first action potential generated by depolarizing current, and the firing patterns of neurons were recorded using step depolarizing currents. Neuronal firing patterns were analyzed using hierarchical clustering, and the active electrical properties of neurons with different firing patterns were compared. Results: A total of 135 neurons from the visual sensory layers of the superior colliculus were successfully recorded. Cluster analysis of the neuronal firing patterns identified three types of firing patterns: tonic firing (97, 72%), phasic firing (26, 19%), and single firing (12, 9%). The number of action potentials for each firing pattern was 13.30±7.38, 3.73±3.61, and 0.83±0.39, respectively, with significant differences (P<0.001). There was no significant difference in the membrane potential response to step currents among the three firing pattern types (P>0.05). The action potential amplitudes were (60.45±12.22), (53.67±13.20), and (44.04± 12.92) mV, and the afterhyperpolarization amplitudes were (13.45±13.79), (12.02±13.11), and (20.75±2.85) mV, respectively. The maximum rising slopes were (171.29±77.46), (130.14±61.83), and (78.89±37.08) V/s, and the maximum falling slopes were (-76.33±33.61), (-68.17±31.65), and (-47.97±13.92) V/s, respectively, with all differences being statistically significant (all P<0.05). There were no significant differences in the resting membrane potential, action potential threshold, half-width, and afterhyperpolarization duration among the three firing pattern types (all P>0.05). Conclusions: In the early postnatal mice, neurons in the visual sensory layers of the superior colliculus exhibit three distinct firing patterns: tonic, phasic, and single firing. These firing pattern types show significant differences in action potential amplitude, afterhyperpolarization amplitude, maximum rising slopes, and maximum falling slopes.
Assuntos
Potenciais de Ação , Camundongos Endogâmicos C57BL , Neurônios , Técnicas de Patch-Clamp , Colículos Superiores , Animais , Camundongos , Masculino , Colículos Superiores/fisiologia , Potenciais de Ação/fisiologia , Neurônios/fisiologia , Fenômenos EletrofisiológicosRESUMO
Cortical processing of auditory information can be affected by interspecies differences as well as brain states. Here we compare multifeature spectro-temporal receptive fields (STRFs) and associated input/output functions or nonlinearities (NLs) of neurons in primary auditory cortex (AC) of four mammalian species. Single-unit recordings were performed in awake animals (female squirrel monkeys, female, and male mice) and anesthetized animals (female squirrel monkeys, rats, and cats). Neuronal responses were modeled as consisting of two STRFs and their associated NLs. The NLs for the STRF with the highest information content show a broad distribution between linear and quadratic forms. In awake animals, we find a higher percentage of quadratic-like NLs as opposed to more linear NLs in anesthetized animals. Moderate sex differences of the shape of NLs were observed between male and female unanesthetized mice. This indicates that the core AC possesses a rich variety of potential computations, particularly in awake animals, suggesting that multiple computational algorithms are at play to enable the auditory system's robust recognition of auditory events.
Assuntos
Córtex Auditivo , Animais , Córtex Auditivo/fisiologia , Feminino , Masculino , Gatos , Camundongos , Ratos , Estimulação Acústica/métodos , Neurônios/fisiologia , Saimiri , Percepção Auditiva/fisiologia , Especificidade da Espécie , Modelos Neurológicos , Potenciais de Ação/fisiologia , Camundongos Endogâmicos C57BLRESUMO
BACKGROUND: Pulsed field ablation (PFA) is a novel technology for catheter-based atrial arrhythmia treatment. Evidence of its application for ventricular arrhythmia ablation is still limited. In this study, we describe the feasibility and efficacy of focal PFA for premature ventricular contraction (PVC) ablation. METHODS: A prospective cohort of 20 patients referred for PVC ablation at 2 centers was enrolled, regardless of the presence of structural heart disease, PVC morphology, or previous ablation attempts. All procedures were performed using the CENTAURI System in combination with contact force sensing catheters and 3-dimensional electroanatomical mapping systems. Energy output and the number of applications were left to the operator's discretion. RESULTS: Eleven (55%) procedures were conducted under general anesthesia, 6 (30%) under deep sedation, and 3 (15%) under light sedation. Muscular contraction was observed in one case (5%). Median procedural and fluoroscopy times were 95.5 and 6.55 minutes, respectively. The median number of PFA applications was 8 with a median contact force of 10g. A statistically significant (76%) reduction was observed in mean peak-to-peak bipolar electrogram voltage before and after ablation (0.707 versus 0.098 mV; P=0.008). Ventricular irritative firing was observed in 11 (55%) patients after PFA. The median follow-up was 120 days. Acute procedural success was achieved in 17 of 20 (85% [95% CI, 0.70-1]) patients. Two of the patients with procedural failure had late success with >80% clinical PVC burden suppression during follow-up, and 2 of 17 patients with acute success had late PVC recurrence, which accounts for a total of 17 of 20 (85% [95% CI, 0.70-1]) patients with chronic success. Transient ST-segment depression occurred in 1 patient, and the right bundle branch block was induced in 2 others (permanently only in one case). CONCLUSIONS: PVC ablation using a focal PFA is feasible, effective, and safe, with promising acute and long-term results in several ventricular locations. Irritative firing is frequently observed. Coronary evaluation should be considered when targeting the outflow tract.