PT  - JOURNAL ARTICLE
AU  - Esmaeilpour, Zeinab
AU  - Jackson, Mark
AU  - Kronberg, Greg
AU  - Zhang, Tianhe
AU  - Esteller, Rosana
AU  - Hershey, Brad
AU  - Bikson, Marom
TI  - Limited Sensitivity of Hippocampal Synaptic Function or Network Oscillations to Unmodulated Kilohertz Electric Fields
AID  - 10.1523/ENEURO.0368-20.2020
DP  - 2020 Nov 01
TA  - eneuro
PG  - ENEURO.0368-20.2020
VI  - 7
IP  - 6
4099  - http://www.eneuro.org/content/7/6/ENEURO.0368-20.2020.short
4100  - http://www.eneuro.org/content/7/6/ENEURO.0368-20.2020.full
SO  - eNeuro2020 Nov 01; 7
AB  - Understanding the cellular mechanisms of kilohertz (kHz) electrical stimulation is of broad interest in neuromodulation including forms of transcranial electrical stimulation, interferential stimulation, and high-rate spinal cord stimulation (SCS). Yet, the well-established low-pass filtering by neuronal membranes suggests minimal neuronal polarization in respond to charge-balanced kHz stimulation. The hippocampal brain slice model is among the most studied systems in neuroscience and exhaustively characterized in screening the effects of electrical stimulation. High-frequency electric fields of varied amplitudes (1–150 V/m), waveforms (sinusoidal, symmetrical pule, asymmetrical pulse) and frequencies (1 and10 kHz) were tested. Changes in single or paired-pulse field EPSPs (fEPSP) in CA1 were measured in response to radial-directed and tangential-directed electric fields, with brief (30 s) or long (30 min) application times. The effects of kHz stimulation on ongoing endogenous network activity were tested in carbachol-induced γ oscillation of CA3a and CA3c. Across 23 conditions evaluated, no significant changes in fEPSP were resolved, while responses were detected for within-slice control direct current (DC) fields; 1-kHz sinusoidal and pulse stimulation (≥60 V/m), but not 10 kHz, induced changes in oscillating neuronal network. We thus report no responses to low-amplitude 1-kHz or any 10-kHz fields, suggesting that any brain sensitivity to these fields is via yet to be-determined mechanism(s) of action which were not identified in our experimental preparation.