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Effects of hyperpolarization-active cation current (Ih) on sublinear dendritic integration under applied electric fields

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Abstract

Evidence shows that distal dendritic polarization induced by electrical fields (EFs) can affect sublinear dendritic integration of AMPA synaptic inputs via modulating the amplitude of excitatory postsynaptic potential that is also influenced by subthreshold active hyperpolarization-active cation current (\(I_{\text{h}}\)). However, it remains unclear how \(I_{\text{h}}\) participates in EF-regulated dendritic integration and then affects the neural input/output relationship. To this end, a two-compartment model was established to depict the effect of \(I_{\text{h}}\) on EF-regulated sublinear dendritic integration as well as its influence on the initiation of action potentials. With the singular perturbation method we found that the equilibrium mapping of the fast subsystem can serve as the asymptotic subthreshold input/output function for EF-regulated sublinear dendritic integration in the presence of \(I_{\text{h}}\). Both theoretical and simulation results showed that the EF-regulated sublinear dendritic integration in the presence of \(I_{\text{h}}\), depending on the biophysical properties of \(I_{\text{h}}\) including conductance and steady-state activation function, becomes more pronounced sublinear for anodal EF stimulation while is more linear for cathodal stimulation. Further, the presence of \(I_{\text{h}}\), independent of EF polarities, reduces the sensitivity of EF modulation effect on dendritic integration via diminishing EF-induced dendritic polarizations. By identifying the respective contribution of EF-regulated dendritic integration and EF-induced somatic polarization to an action potential generation in the presence of \(I_{\text{h}}\), we found that \(I_{\text{h}}\) inhibits the initiation of action potential no matter of EF polarities, which is, respectively, attributed to the \(I_{\text{h}}\) activation-induced more pronounced sublinear dendritic integration in the presence of anodal EF and the \(I_{\text{h}}\) inactivation-induced larger somatic hyperpolarization in the case of cathodal EF. These findings suggest that the specific modulatory influence of EF on brain activities not only depends on the EF parameters but also relies on the neural intrinsic properties.

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Funding

This work was supported by the National Natural Science Foundation of China under Grant 62171312, 61771330, 62071324, and the Tianjin Municipal Natural Science Foundation under Grant 19JCQNJC01200.

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Authors and Affiliations

  1. Tianjin Key Laboratory of Process Measurement and Control, School of Electrical and Information Engineering, Tianjin University, Tianjin, China

    Yaqin Fan, Xile Wei, Guosheng Yi & Jiang Wang

  2. School of Information Technology Engineering, Tianjin University of Technology and Education, Tianjin, 300222, China

    Meili Lu

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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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Correspondence to Guosheng Yi.

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Supplementary Information

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11071_2022_7427_MOESM1_ESM.docx

Supplementary file1. In Sect. 1, we introduced the detailed parameters of STC-PYN-AMPA with S1 Table. In Sect. 2, we introduced the detailed parameters of active ionic currents of a biophysical layer 5 pyramidal neuron with S2 Table. In Sect. 3, we introduced the detailed parameters of multi current clamp stimulation used for repolarizing resting potential as changes with S3 Table. (DOCX 99 KB)

11071_2022_7427_MOESM2_ESM.docx

Supplementary file2. In Sect. 1, we showed the effect of on EF-regulated dendritic integration of NMDA synapses with the layer 5 pyramidal neuron introduced in Materials and Methods, as shown in S1 Fig. In Sect. 2, we studied the effect of on EF-regulated sublinear dendritic integration with a biophysical pyramidal model in CA1 that has increasing from soma to distal dendrites, as shown in S2 Fig. (DOCX 153 KB)

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Fan, Y., Wei, X., Yi, G. et al. Effects of hyperpolarization-active cation current (Ih) on sublinear dendritic integration under applied electric fields. Nonlinear Dyn 108, 4335–4356 (2022). https://doi.org/10.1007/s11071-022-07427-1

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