Department of Neuroscience, Baylor College of Medicine, Houston, TX, USA.
Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX, USA.
Nat Commun. 2021 Mar 9;12(1):1539. doi: 10.1038/s41467-021-21730-2.
Vagus nerve stimulation (VNS) is thought to affect neural activity by recruiting brain-wide release of neuromodulators. VNS is used in treatment-resistant epilepsy, and is increasingly being explored for other disorders, such as depression, and as a cognitive enhancer. However, the promise of VNS is only partially fulfilled due to a lack of mechanistic understanding of the transfer function between stimulation parameters and neuromodulatory response, together with a lack of biosensors for assaying stimulation efficacy in real time. We here develop an approach to VNS in head-fixed mice on a treadmill and show that pupil dilation is a reliable and convenient biosensor for VNS-evoked cortical neuromodulation. In an 'optimal' zone of stimulation parameters, current leakage and off-target effects are minimized and the extent of pupil dilation tracks VNS-evoked basal-forebrain cholinergic axon activity in neocortex. Thus, pupil dilation is a sensitive readout of the moment-by-moment, titratable effects of VNS on brain state.
迷走神经刺激（Vagus nerve stimulation，VNS）被认为通过招募神经调质的全脑释放来影响神经活动。VNS 用于治疗耐药性癫痫，并且越来越多地被探索用于其他疾病，如抑郁症，以及作为认知增强剂。然而，由于对刺激参数和神经调质反应之间的传递函数缺乏机制理解，以及缺乏用于实时检测刺激效果的生物传感器，VNS 的承诺仅部分实现。我们在这里开发了一种在跑步机上固定头部的小鼠的 VNS 方法，并表明瞳孔扩张是 VNS 诱发皮质神经调制的可靠和方便的生物传感器。在刺激参数的“最佳”区域中，电流泄漏和靶外效应最小化，并且瞳孔扩张的程度跟踪 VNS 诱发的新皮层基底前脑胆碱能轴突活动。因此，瞳孔扩张是 VNS 对大脑状态的瞬间、可滴定影响的敏感读数。
