Wang Runming, Fridman Gene
bioRxiv. 2025 Jun 21:2025.06.19.660597. doi: 10.1101/2025.06.19.660597.
Excitability is a fundamental property of cortical networks, shaping their responses to input. Here, we use ionic direct current (iDC) to modulate excitability with sub-10-ms temporal resolution and submillimeter spatial precision across the cortical surface, greatly surpassing the capabilities of pharmacological tools. In anesthetized rats, we recorded laminar neural responses in the S1HL cortex to spontaneous delta oscillations and to foot stimulation with and without iDC delivered to the cortical surface. Cathodic iDC suppressed, and anodic iDC enhanced, evoked responses across recording sites. iDC shifted the spatiotemporal excitability pattern in a graded manner, paralleling the effects of weaker or stronger foot stimuli. A computational model reproduced these effects and implicated dendritic summation at the axon initial segment (AIS) as a key mechanism for bidirectional modulation. This approach enables precise, causal manipulation of cortical responsiveness in vivo and offers a platform for dissecting functional circuits and developing targeted neurotherapeutic interventions.
兴奋性是皮层网络的一项基本属性，它塑造了皮层网络对输入的反应。在此，我们使用离子直流电（iDC）以亚10毫秒的时间分辨率和跨皮层表面亚毫米级的空间精度来调节兴奋性，这大大超越了药理学工具的能力。在麻醉大鼠中，我们记录了初级躯体感觉皮层（S1HL）中不同层面对自发δ振荡以及在向皮层表面施加或不施加iDC情况下足部刺激的神经反应。阴极iDC抑制、阳极iDC增强记录位点的诱发反应。iDC以分级方式改变时空兴奋性模式，这与较弱或较强足部刺激的效果相似。一个计算模型再现了这些效应，并表明轴突起始段（AIS）处的树突总和是双向调制的关键机制。这种方法能够在体内对皮层反应性进行精确的因果操纵，并为剖析功能回路和开发有针对性的神经治疗干预提供了一个平台。
