Closed‐Loop Optogenetic Modulation of Neural Activities in Freely Moving Mice with Multimodal Fibers

Abstract The precise manipulation of neural activity is of great significance to reveal the function of complex neural circuits in brain, especially the mechanism of neurological disorders such as epilepsy, Parkinson's, and Alzheimer's disease. In the past decades, optogenetics has become a powerful tool to investigate the function of neural circuits due to its unique advantages of cell specificity and high spatiotemporal resolution. However, to date, most optogenetic manipulation has been conducted in an open‐loop fashion. The closed‐loop neural modulation is still an important task. Here, a closed‐loop optogenetic modulation system is developed for ultra‐fast, ‐accurate, and ‐stable manipulation of neural activities in behaving mice. Specifically, this system is mediated by a functional fiber probe with excellent low optical loss (0.052 dB cm−1 at 589 nm) and electrical impedance (5.40 MΩ µm−2 at 1 kHz). In vivo electrophysiology and behavioral experiments demonstrated that the system can be successfully applied for the identification and intervention of seizures in epilepsy mice with high efficiency. It is envision that the closed‐loop manipulation system has promising applications in brain science, neuroscience, and neuromodulation therapies.