RESUMEN
Objective.Commonly used cable equation approaches for simulating the effects of electromagnetic fields on excitable cells make several simplifying assumptions that could limit their predictive power. Bidomain or 'whole' finite element methods have been developed to fully couple cells and electric fields for more realistic neuron modeling. Here, we introduce a novel bidomain integral equation designed for determining the full electromagnetic coupling between stimulation devices and the intracellular, membrane, and extracellular regions of neurons.Approach.Our proposed boundary element formulation offers a solution to an integral equation that connects the device, tissue inhomogeneity, and cell membrane-induced E-fields. We solve this integral equation using first-order nodal elements and an unconditionally stable Crank-Nicholson time-stepping scheme. To validate and demonstrate our approach, we simulated cylindrical Hodgkin-Huxley axons and spherical cells in multiple brain stimulation scenarios.Main Results.Comparison studies show that a boundary element approach produces accurate results for both electric and magnetic stimulation. Unlike bidomain finite element methods, the bidomain boundary element method does not require volume meshes containing features at multiple scales. As a result, modeling cells, or tightly packed populations of cells, with microscale features embedded in a macroscale head model, is simplified, and the relative placement of devices and cells can be varied without the need to generate a new mesh.Significance.Device-induced electromagnetic fields are commonly used to modulate brain activity for research and therapeutic applications. Bidomain solvers allow for the full incorporation of realistic cell geometries, device E-fields, and neuron populations. Thus, multi-cell studies of advanced neuronal mechanisms would greatly benefit from the development of fast-bidomain solvers to ensure scalability and the practical execution of neural network simulations with realistic neuron morphologies.
Asunto(s)
Campos Electromagnéticos , Análisis de Elementos Finitos , Modelos Neurológicos , Neuronas , Neuronas/fisiología , Neuronas/efectos de la radiación , Humanos , Simulación por Computador , Animales , Axones/fisiología , Axones/efectos de la radiación , Potenciales de Acción/fisiología , Potenciales de Acción/efectos de la radiación , Encéfalo/fisiologíaRESUMEN
The fine control of synaptic function requires robust trans-synaptic molecular interactions. However, it remains poorly understood how trans-synaptic bridges change to reflect the functional states of the synapse. Here, we develop optical tools to visualize in firing synapses the molecular behavior of two trans-synaptic proteins, LGI1 and ADAM23, and find that neuronal activity acutely rearranges their abundance at the synaptic cleft. Surprisingly, synaptic LGI1 is primarily not secreted, as described elsewhere, but exo- and endocytosed through its interaction with ADAM23. Activity-driven translocation of LGI1 facilitates the formation of trans-synaptic connections proportionally to the history of activity of the synapse, adjusting excitatory transmission to synaptic firing rates. Accordingly, we find that patient-derived autoantibodies against LGI1 reduce its surface fraction and cause increased glutamate release. Our findings suggest that LGI1 abundance at the synaptic cleft can be acutely remodeled and serves as a critical control point for synaptic function.
Asunto(s)
Péptidos y Proteínas de Señalización Intracelular , Sinapsis , Transmisión Sináptica , Transmisión Sináptica/fisiología , Humanos , Sinapsis/metabolismo , Animales , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Ratones , Ácido Glutámico/metabolismo , Transporte de Proteínas , Masculino , Proteínas ADAM/metabolismo , Neuronas/metabolismo , Autoanticuerpos/inmunología , Ratones Endogámicos C57BLRESUMEN
Objective: Commonly used cable equation-based approaches for determining the effects of electromagnetic fields on excitable cells make several simplifying assumptions that could limit their predictive power. Bidomain or "whole" finite element methods have been developed to fully couple cells and electric fields for more realistic neuron modeling. Here, we introduce a novel bidomain integral equation designed for determining the full electromagnetic coupling between stimulation devices and the intracellular, membrane, and extracellular regions of neurons. Methods: Our proposed boundary element formulation offers a solution to an integral equation that connects the device, tissue inhomogeneity, and cell membrane-induced E-fields. We solve this integral equation using first-order nodal elements and an unconditionally stable Crank-Nicholson time-stepping scheme. To validate and demonstrate our approach, we simulated cylindrical Hodgkin-Huxley axons and spherical cells in multiple brain stimulation scenarios. Main Results: Comparison studies show that a boundary element approach produces accurate results for both electric and magnetic stimulation. Unlike bidomain finite element methods, the bidomain boundary element method does not require volume meshes containing features at multiple scales. As a result, modeling cells, or tightly packed populations of cells, with microscale features embedded in a macroscale head model, is made computationally tractable, and the relative placement of devices and cells can be varied without the need to generate a new mesh. Significance: Device-induced electromagnetic fields are commonly used to modulate brain activity for research and therapeutic applications. Bidomain solvers allow for the full incorporation of realistic cell geometries, device E-fields, and neuron populations. Thus, multi-cell studies of advanced neuronal mechanisms would greatly benefit from the development of fast-bidomain solvers to ensure scalability and the practical execution of neural network simulations with realistic neuron morphologies.