Accurate evaluation of neural sensitivity to weak alternating electric fields requires protocols accounting for input dependence

Background: Weak alternating electric fields (∼1 V/m) modulate nervous system activity. Yet, the exact mechanism by which such low amplitude electric fields can modulate neural activity is still unknown despite the use of specific protocols aiming at quantifying neural sensitivity. Objective: To characterize how the measurement protocol can impact neural sensitivity to weak electric fields and bias in vivo sensitivity. Methods: We considered a variety of somatic clamp stimulation to drive the activity of biophysical morpho-realistic reconstructed neurons during extracellular alternating stimulation to quantify the sensitivity to the field depending on the nature of cells’ activity. Results: Cells sensitivity to alternating current stimulation depended on the type of input used to drive their activity, with a different frequency response for each protocol, with a trend for inhibitory neurons to be more sensitive to higher stimulation frequencies. Even with the same clamp protocol, sensitivity depended on the statistics of the input used. Significance: Neuronal sensitivity to alternating current stimulation is highly input-dependent, which has been largely neglected so far, and depends on the current statistic of the received inputs, and is not reliably represented by simple current clamps protocols.