Abstract

The rise of transcranial current stimulation (tCS) techniques have sparked an increasing interest in the effects of weak extracellular electric fields on neural activity. These fields modulate ongoing neural activity through polarization of the neuronal membrane. While the somatic polarization has been investigated experimentally, the frequency-dependent polarization of the dendritic trees in the presence of alternating (AC) fields has received little attention yet. Using a biophysically detailed model with experimentally constrained active conductances, we analyze the subthreshold response of cortical pyramidal cells to weak AC fields, as induced during tCS. We observe a strong frequency resonance around 10-20 Hz in the apical dendrites sensitivity to polarize in response to electric fields but not in the basal dendrites nor the soma. To disentangle the relative roles of the cell morphology and active and passive membrane properties in this resonance, we perform a thorough analysis using simplified models, e.g. a passive pyramidal neuron model, simple passive cables and reconstructed cell model with simplified ion channels. We attribute the origin of the resonance in the apical dendrites to (i) a locally increased sensitivity due to the morphology and to (ii) the high density of h-type channels. Our systematic study provides an improved understanding of the subthreshold response of cortical cells to weak electric fields and, importantly, allows for an improved design of tCS stimuli.

Highlights

  • In the past decade, evidence of ephaptic coupling [1, 2](see [3] for a review) and the dawn of transcranial current stimulation have sparked an increasing interest in the modulation of neuronal activity through weak extracellular fields. tCS can modulate ongoing neural activity [4] and cognitive capacity, e.g. to potentiate memory [5], and its non-invasiveness provides it with a great potential for clinical applications

  • When subject to a Direct Current (DC) field, the apical dendrites get oppositely polarized compared to the soma and basal dendrites (Fig 1A, 1B and 1C)

  • In agreement with previous studies [8, 9] we found an opposite polarization in the apical dendrites compared to the soma and basal dendrites of a passive pyramidal cell model, i.e., with all active conductances removed

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Summary

Introduction

Evidence of ephaptic coupling [1, 2](see [3] for a review) and the dawn of transcranial current stimulation (tCS) have sparked an increasing interest in the modulation of neuronal activity through weak extracellular fields. tCS can modulate ongoing neural activity [4] and cognitive capacity, e.g. to potentiate memory [5], and its non-invasiveness provides it with a great potential for clinical applications. TCS makes use of the application of low amplitude direct (tDCS) or alternating (tACS) current on the scalp. This current induces a weak extracellular electric field within the brain [6]. Weak uniform electric field have been shown to induce inward and outward membrane currents at different cell locations [8]. This results in a non-uniform membrane polarization of the neuron (in the order of 0.1 mV per V/m) [9]. Little is known about the frequencydependence of the polarization in the dendritic tree, which is where virtually all synaptic input to a neuron arrives and which is endowed with many active, voltage-dependent processes [15] that might be modulated by extracellular fields

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