Seizures are made up of the coordinated activity of networks of neurons, suggesting that control of neurons in the pathologic circuits of epilepsy could allow for control of the disease. Optogenetics has been effective at stopping seizure-like activity in non-human disease models by increasing inhibitory tone or decreasing excitation, although this effect has not been shown in human brain tissue. Many of the genetic means for achieving channelrhodopsin expression in non-human models are not possible in humans, and vector-mediated methods are susceptible to species-specific tropism that may affect translational potential. Here we demonstrate adeno-associated virus–mediated, optogenetic reductions in network firing rates of human hippocampal slices recorded on high-density microelectrode arrays under several hyperactivity-provoking conditions. This platform can serve to bridge the gap between human and animal studies by exploring genetic interventions on network activity in human brain tissue.

癫痫发作由神经元网络的协调活动组成，这表明对癫痫病理回路中神经元的控制可以控制疾病。光遗传学通过增加抑制性张力或减少兴奋，在非人类疾病模型中有效地阻止癫痫样活动，尽管这种效果尚未在人脑组织中显示。在非人类模型中实现通道视紫红质表达的许多遗传手段在人类中是不可能的，并且载体介导的方法容易受到可能影响翻译潜力的物种特异性趋向性的影响。在这里，我们展示了在几种多动刺激条件下，高密度微电极阵列上记录的人类海马切片网络放电率的腺相关病毒介导的光遗传学降低。该平台可以通过探索对人类脑组织中网络活动的遗传干预来弥合人类和动物研究之间的差距。