Frequency-dependent membrane polarization across neocortical cell types and subcellular elements by transcranial...

Area of Science:

• Neuroscience
• Computational Neuroscience
• Biophysics

Background:

• Transcranial alternating current stimulation (tACS) is a non-invasive brain stimulation technique.
• tACS interacts with brain oscillations in a frequency-dependent manner.
• Cellular effects of tACS across different neuron types and subcellular components remain unclear.

Purpose of the Study:

• To simulate and characterize the cellular response of neocortical neurons to electric fields (EFs) used in tACS.
• To investigate how membrane polarization varies with EF direction, intensity, and frequency across different cell types and subcellular elements.

Main Methods:

• Utilized morphologically realistic computational models of neocortical neurons.
• Simulated responses to uniform oscillating electric fields (EFs).
• Systematically analyzed membrane polarization in soma, axons, and dendrites under varying stimulation parameters.

Main Results:

• Pyramidal cells showed higher sensitivity to axial EFs parallel to cortical columns; interneurons responded to axial and transverse EFs.
• Membrane polarization scaled linearly with EF intensity, with frequency-dependent polarization length.
• Pyramidal cells exhibited greater polarization than interneurons; axons were most polarized, followed by dendrites and soma.
• Apical dendrites of pyramidal cells displayed frequency resonance, while other elements showed low-pass filtering; interneuron elements had complex frequency responses.
• Polarization phase lagged the EF, exhibiting high-pass filtering properties.

Conclusions:

• Membrane polarization during tACS is specific to cell type, subcellular element, and stimulation frequency.
• Cell morphology and biophysics are critical determinants of frequency-dependent membrane polarization.
• Findings offer insights into tACS cellular mechanisms and their impact on neural activity.