Ionic Direct Current Enables Millimeter- and Millisecond-Scale Cortical Gain Control in vivo

Precise, reversible modulation of cortical gain at mesoscale resolution remains a major challenge for neuroscience. Here, we introduce ionic direct current (iDC) delivered through non-penetrating electrolyte-filled microcatheters on the cortical surface as a method for targeted neuromodulation at millimeter spatial scales and millisecond onset/offset. In rat primary somatosensory cortex (S1HL), laminar recordings under urethane revealed that cathodic iDC attenuated and anodic iDC amplified both spontaneous delta oscillations and sensory-evoked responses, without causing time-locked spiking or state disruption. Computational modeling reproduced these effects and implicated dendritic summation at the axon initial segment as the mechanism for bidirectional gain control. In awake animals, iDC modulation of S1HL altered tactile sensitivity to Von Frey stimulation, demonstrating behavioral relevance. Together, these results establish iDC as a versatile platform for precise, rapidly reversible, and non-disruptive manipulation of cortical gain in vivo, enabling new approaches for dissecting mesoscale circuit interactions and linking column-scale physiology to behavior.