Field-Sensitive Axon Initial Segment Polarization by IonicDirect Current Dissociates Gain Modulation from TemporalStructure in Cortical Circuits

Abstract

Conventional implantable neuromodulation relies on brief electrical or optical pulses that directly evoke action potentials in targeted neurons. While powerful, such approaches primarily impose activity rather than modulate how circuits process ongoing signals. Here, we introduce ionic direct current (iDC) delivered through non-penetrating, electrolyte-filled microcatheters on the cortical surface as an alternative strategy for neuromodulation that adjusts cortical gain without directly driving spikes. In rat primary somatosensory cortex, laminar recordings showed that cathodic iDC attenuated and anodic iDC amplified spontaneous and sensory-evoked activity while preserving the temporal structure of population responses. Computational modeling implicated polarization at the axon initial segment as the mechanism underlying bidirectional gain control. In awake animals, iDC modulation altered tactile sensitivity, demonstrating behavioral relevance. These findings establish iDC as a rapidly reversible, spatially precise method for modulating cortical processing, offering a fundamentally different mode of neuromodulation that bridges circuit physiology and behavior without overriding native neural dynamics. TEASERIonic direct current modulates cortical gain via subthreshold polarization, preserving native neural dynamics.