Effects of frequency-dependent membrane capacitance on neural excitability

Area of Science:

• Computational Neuroscience
• Biophysics
• Electrophysiology

Background:

• Standard models assume constant membrane capacitance, but experiments reveal frequency-dependent capacitance (c(f)) with dispersion.
• Understanding c(f) is crucial for accurate neural modeling, especially with emerging kHz stimulation techniques.

Purpose of the Study:

• To quantify the effects of frequency-dependent membrane capacitance (c(f)) on neural excitability.
• To analyze the impact of c(f) across a wide frequency range (dc to hundreds of kHz) on various neuronal models.

Main Methods:

• Implemented a circuit model of c(f) using linear elements.
• Incorporated c(f) into Hodgkin-Huxley (unmyelinated axon), MRG (myelinated axon), and PFC cortical neuron models.
• Calculated excitation thresholds, kHz conduction block, conduction velocity, recovery cycle, strength-distance relationship, and firing rate.

Main Results:

• c(f) effects on thresholds varied with stimulation waveform and channel kinetics; significant only for MRG model with sinusoidal signals >10 kHz.
• Conduction velocity increased (up to 7.9% myelinated, 1.7% unmyelinated); block thresholds decreased moderately (max 11.5%) at higher frequencies.
• Minimal impact on recovery cycle and strength-distance relationship; firing patterns altered marginally (<2% ISI reduction).

Conclusions:

• This is the first comprehensive analysis of dispersive capacitance effects on neural excitability.
• Identifies critical frequency ranges where c(f) must be considered for accurate neural modeling, particularly for kHz stimulation.