Abstract
Evidence shows that the dendritic polarization induced by weak electrical field (EF) can affect the neuronal input–output function via modulating dendritic integration of AMPA synapses, indicating that the supralinear dendritic integration of NMDA synapses can also be influenced by dendritic polarization. However, it remains unknown how dendritic polarization affects NMDA-type dendritic integration, and then contributes to neuronal input–output relationship. Here, we used a computational model of pyramidal neuron with inhomogeneous extracellular potentials to characterize the relationship among EF, dendritic integration, and somatic output. Basing on singular perturbation we analyzed the subthreshold dynamics of membrane potentials in response to NMDA synapses, and found that the equilibrium mapping of a fast subsystem can characterize the asymptotic subthreshold input–output (sI/O) relationship for EF-regulated supralinear dendritic integration, allowing us to predict the tendency of EF-regulated dendritic integration by showing the variation of equilibrium mapping under EF stimulation. EF-induced depolarization at distal dendrites receiving synapses plays a crucial role in shifting the steep change of sI/O left by facilitating dendritic NMDA spike generation and in decreasing the plateau of sI/O via reducing driving force. And more effective EF modulation appears at sparsely activated NMDA receptors compared with clustered synaptic inputs. During the action potential (AP) generation, the respective contribution of EF-regulated dendritic integration and EF-induced somatic polarization was identified to show their synergetic or antagonistic effect on AP generation, depending on neuronal excitability. These results provided insight in understanding the modulation effect of EF on neuronal computation, which is important for optimizing noninvasive brain stimulation.
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Acknowledgements
This work was supported by the National Natural Science Foundation of China under Grant 62171312, 62071324, and the Tianjin Municipal Natural Science Foundation under Grant 19JCQNJC01200.
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This study was funded by the National Natural Science Foundation of China under Grant 62171312, 62071324, and the Tianjin Municipal Natural Science Foundation under Grant 19JCQNJC01200.
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All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by YF. The first draft of the manuscript was written by YF and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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11571_2022_9922_MOESM1_ESM.docx
S1 File: In section 1, we introduced the detailed parameters of SCM-PYN-NMDA with S1 Table. In section 2, we introduced the detailed parameters of active ionic currents of a biophysical layer 5 pyramidal neuron with S2 Table. In section 3, we introduced the detailed parameters of multi current clamp stimulation used to mimic EF stimulations in different cases with S3 Table, S4 Table, S5 Table, S6 Table. (DOCX 68 kb)
11571_2022_9922_MOESM2_ESM.docx
S2 File: The detail derivation process about how to analyze and obtain the equilibrium point of SCM-PYN-NMDA. (DOCX 187 kb)
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Fan, Y., Wei, X., Lu, M. et al. Electric field effects on neuronal input–output relationship by regulating NMDA spikes. Cogn Neurodyn 18, 199–215 (2024). https://doi.org/10.1007/s11571-022-09922-y
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DOI: https://doi.org/10.1007/s11571-022-09922-y