Program in Biomedical Engineering, SUNY Downstate Health Sciences University and NYU Tandon School of Engineering, Brooklyn, New York.
Department of Physiology and Pharmacology, SUNY Downstate Health Sciences University, Brooklyn, New York.
J Neurophysiol. 2021 Apr 1;125(4):1501-1516. doi: 10.1152/jn.00015.2021. Epub 2021 Mar 10.
Pyramidal neurons in neocortex have complex input-output relationships that depend on their morphologies, ion channel distributions, and the nature of their inputs, but which cannot be replicated by simple integrate-and-fire models. The impedance properties of their dendritic arbors, such as resonance and phase shift, shape neuronal responses to synaptic inputs and provide intraneuronal functional maps reflecting their intrinsic dynamics and excitability. Experimental studies of dendritic impedance have shown that neocortical pyramidal tract neurons exhibit distance-dependent changes in resonance and impedance phase with respect to the soma. We, therefore, investigated how well several biophysically detailed multicompartment models of neocortical layer 5 pyramidal tract neurons reproduce the location-dependent impedance profiles observed experimentally. Each model tested here exhibited location-dependent impedance profiles, but most captured either the observed impedance amplitude or phase, not both. The only model that captured features from both incorporates hyperpolarization-activated cyclic nucleotide-gated (HCN) channels and a shunting current, such as that produced by Twik-related acid-sensitive K (TASK) channels. TASK-like channel density in this model was proportional to local HCN channel density. We found that although this shunting current alone is insufficient to produce resonance or realistic phase response, it modulates all features of dendritic impedance, including resonance frequencies, resonance strength, synchronous frequencies, and total inductive phase. We also explored how the interaction of HCN channel current () and a TASK-like shunting current shape synaptic potentials and produce degeneracy in dendritic impedance profiles, wherein different combinations of and shunting current can produce the same impedance profile. We simulated chirp current stimulation in the apical dendrites of 5 biophysically detailed multicompartment models of neocortical pyramidal tract neurons and found that a combination of HCN channels and TASK-like channels produced the best fit to experimental measurements of dendritic impedance. We then explored how HCN and TASK-like channels can shape the dendritic impedance as well as the voltage response to synaptic currents.
新皮层中的锥体神经元具有复杂的输入-输出关系，这取决于它们的形态、离子通道分布以及输入的性质，但这些关系不能通过简单的积分-点火模型来复制。它们树突分支的阻抗特性，如共振和相移，会影响神经元对突触输入的反应，并提供反映其内在动力学和兴奋性的神经元内功能图。对树突阻抗的实验研究表明，新皮层锥体束神经元表现出与胞体的距离相关的共振和阻抗相位变化。因此，我们研究了几种新皮层第 5 层锥体束神经元的详细生物物理多室模型在多大程度上再现了实验中观察到的位置相关阻抗谱。这里测试的每个模型都表现出位置相关的阻抗谱，但大多数模型只捕捉到观察到的阻抗幅度或相位，而不是两者都捕捉到。唯一同时捕捉到这两个特征的模型包含超极化激活环核苷酸门控 (HCN) 通道和一种分流电流，如由 Twik 相关酸敏感 K (TASK) 通道产生的电流。该模型中的 TASK 样通道密度与局部 HCN 通道密度成正比。我们发现，尽管这种分流电流本身不足以产生共振或现实的相位响应，但它可以调节树突阻抗的所有特征，包括共振频率、共振强度、同步频率和总电感相位。我们还探索了 HCN 通道电流 () 和 TASK 样分流电流如何相互作用来塑造突触电位并产生树突阻抗谱的简并性，其中不同的 和分流电流组合可以产生相同的阻抗谱。我们在 5 种新皮层锥体束神经元的详细生物物理多室模型的树突顶进行了啁啾电流刺激模拟，发现 HCN 通道和 TASK 样通道的组合与树突阻抗的实验测量结果拟合得最好。然后，我们探索了 HCN 和 TASK 样通道如何塑造树突阻抗以及对突触电流的电压响应。
