Low-intensity ultrasound drives offline neuromodulation through passive membrane mechanisms in synaptically isolated hippocampal neurons

Abstract

Low-intensity ultrasound alters neuronal excitability long after exposure ends, but the basis of this offline effect is unclear and most proposed mechanisms require synaptic receptors. We recorded from cultured mouse hippocampal neurons in whole-cell current clamp, before and 20 min after 1 min of 850 kHz continuous-wave ultrasound at 0.5 W/cm2 or sham, with synaptic transmission blocked throughout, each neuron re-patched. Sonicated neurons remained intact and firing, yet depolarized, with smaller action potentials and more noise. A passive-membrane fit showed reduced capacitance and a depolarized leak reversal potential in every sonicated cell, with a shortened time constant and no detectable change in input conductance, while sham cells showed no significant change. Changes in the time constant and reversal potential, both independent of membrane area, indicate a modification of the membrane itself rather than a loss of area. Brief ultrasound therefore leaves a lasting, receptor-independent imprint on passive membrane properties.