Evidences show that electric fields(EFs)induced by the magnetic stimulation could modulates brain activities by regulating the excitability of GABAergic interneuron.However,it is still unclear how and why the EF-induc...Evidences show that electric fields(EFs)induced by the magnetic stimulation could modulates brain activities by regulating the excitability of GABAergic interneuron.However,it is still unclear how and why the EF-induced polarization affects the interneuron response as the interneuron receives NMDA synaptic inputs.Considering the key role of NMDA receptor-mediated supralinear dendritic integration in neuronal computations,we suppose that the applied EFs could functionally modulate interneurons’response via regulating dendritic integration.At first,we build a simplified multi-dendritic circuit model with inhomogeneous extracellular potentials,which characterizes the relationship among EF-induced spatial polarizations,dendritic integration,and somatic output.By performing model-based singular perturbation analysis,it is found that the equilibrium point of fast subsystem can be used to asymptotically depict the subthreshold input–output(sI/O)relationship of dendritic integration.It predicted that EF-induced strong depolarizations on the distal dendrites reduce the dendritic saturation output by reducing driving force of synaptic input,and it shifts the steep change of sI/O curve left by reducing stimulation threshold of triggering NMDA spike.Also,the EF modulation prefers the global dendritic integration with asymmetric scatter distribution of NMDA synapses.Furthermore,we identify the respective contribution of EF-regulated dendritic integration and EF-induced somatic polarization to an action potential generation and find that they have an antagonistic effect on AP generation due to the varied NMDA spike threshold under EF stimulation.展开更多
Coexistence of fast and slow traveling waves without synaptic transmission has been found in hhhippocampal tissues,which is closely related to both normal brain activity and abnormal neural activity such as epileptic ...Coexistence of fast and slow traveling waves without synaptic transmission has been found in hhhippocampal tissues,which is closely related to both normal brain activity and abnormal neural activity such as epileptic discharge. However, the propagation mechanism behind this coexistence phenomenon remains unclear. In this paper, a three-dimensional electric field coupled hippocampal neural network is established to investigate generation of coexisting spontaneous fast and slow traveling waves. This model captures two types of dendritic traveling waves propagating in both transverse and longitude directions: the N-methyl-D-aspartate(NMDA)-dependent wave with a speed of about 0.1 m/s and the Ca-dependent wave with a speed of about 0.009 m/s. These traveling waves are synaptic-independent and could be conducted only by the electric fields generated by neighboring neurons, which are basically consistent with the in vitro data measured experiments. It is also found that the slow Ca wave could trigger generation of fast NMDA waves in the propagation path of slow waves whereas fast NMDA waves cannot affect the propagation of slow Ca waves. These results suggest that dendritic Ca waves could acted as the source of the coexistence fast and slow waves. Furthermore, we also confirm the impact of cellular spacing heterogeneity on the onset of coexisting fast and slow waves. The local region with decreasing distances among neighbor neurons is more liable to promote the onset of spontaneous slow waves which, as sources, excite propagation of fast waves. These modeling studies provide possible biophysical mechanisms underlying the neural dynamics of spontaneous traveling waves in brain tissues.展开更多
基金Project supported by the National Natural Science Foundation of China(Grant No.62171312)the Tianjin Municipal Education Commission Scientific Research Project,China(Grant No.2020KJ114).
文摘Evidences show that electric fields(EFs)induced by the magnetic stimulation could modulates brain activities by regulating the excitability of GABAergic interneuron.However,it is still unclear how and why the EF-induced polarization affects the interneuron response as the interneuron receives NMDA synaptic inputs.Considering the key role of NMDA receptor-mediated supralinear dendritic integration in neuronal computations,we suppose that the applied EFs could functionally modulate interneurons’response via regulating dendritic integration.At first,we build a simplified multi-dendritic circuit model with inhomogeneous extracellular potentials,which characterizes the relationship among EF-induced spatial polarizations,dendritic integration,and somatic output.By performing model-based singular perturbation analysis,it is found that the equilibrium point of fast subsystem can be used to asymptotically depict the subthreshold input–output(sI/O)relationship of dendritic integration.It predicted that EF-induced strong depolarizations on the distal dendrites reduce the dendritic saturation output by reducing driving force of synaptic input,and it shifts the steep change of sI/O curve left by reducing stimulation threshold of triggering NMDA spike.Also,the EF modulation prefers the global dendritic integration with asymmetric scatter distribution of NMDA synapses.Furthermore,we identify the respective contribution of EF-regulated dendritic integration and EF-induced somatic polarization to an action potential generation and find that they have an antagonistic effect on AP generation due to the varied NMDA spike threshold under EF stimulation.
基金supported in part by the National Natural Science Foundation of China (Grant Nos. 62171312 and 61771330)the Tianjin Municipal Education Commission Scientific Research Project (Grant No. 2020KJ114)。
文摘Coexistence of fast and slow traveling waves without synaptic transmission has been found in hhhippocampal tissues,which is closely related to both normal brain activity and abnormal neural activity such as epileptic discharge. However, the propagation mechanism behind this coexistence phenomenon remains unclear. In this paper, a three-dimensional electric field coupled hippocampal neural network is established to investigate generation of coexisting spontaneous fast and slow traveling waves. This model captures two types of dendritic traveling waves propagating in both transverse and longitude directions: the N-methyl-D-aspartate(NMDA)-dependent wave with a speed of about 0.1 m/s and the Ca-dependent wave with a speed of about 0.009 m/s. These traveling waves are synaptic-independent and could be conducted only by the electric fields generated by neighboring neurons, which are basically consistent with the in vitro data measured experiments. It is also found that the slow Ca wave could trigger generation of fast NMDA waves in the propagation path of slow waves whereas fast NMDA waves cannot affect the propagation of slow Ca waves. These results suggest that dendritic Ca waves could acted as the source of the coexistence fast and slow waves. Furthermore, we also confirm the impact of cellular spacing heterogeneity on the onset of coexisting fast and slow waves. The local region with decreasing distances among neighbor neurons is more liable to promote the onset of spontaneous slow waves which, as sources, excite propagation of fast waves. These modeling studies provide possible biophysical mechanisms underlying the neural dynamics of spontaneous traveling waves in brain tissues.
