Wireless Optical Stimulator And Closed-Loop Modulation System For Optogenetics Research

Optogenetics has become a novel neuromodulation technology by providing precise stimulation with high spatiotemporal resolution. Traditional research of optogenetics mainly based on laser, fiber and electroencephalogram(EEG) acquisition system. However, these tethered fiber-optic approaches have restricted the applications of the technique on neuromodulation on small freely moving animal in vivo. Moreover, as the trend of modulation related optogenetics developing toward closed-loop control, there was an urgent need for integrated system combining optical simulation and EEG acquisition, which could provide rich data for closed-loop strategy. Thus, this paper presented a miniaturized, wirelessly optical stimulator and a closed-loop system integrating simulation and recording.Firstly, a multi-channel, miniaturized and wirelessly programmed optical stimulator was developed, which consisted of 4 components.(1) Software developed in LabVIEW for adjusting stimulation parameter.(2) A wireless transmitter based on nRF51822 used for connecting software and the stimulator.(3) The stimulator was implemented by nRF51822, an ultra-low power 2.4 GHz wireless system on chip, which was suitable for little data transform and small size model. LED was derived by MBI5036 with 64-order brightness adjustment.(4) An implantable optrode assembled with 460 nm u LED for stimulation.Secondly, we developed a closed-loop system combining optical stimulating and EEG recording, to transmit EEG data to software which was then stored on PC. The system was composed of four components.(1) Software for EEG displaying and data storing.(2) Wireless module based on CP2102 and nRF24L01 for connecting software and simulating-sensing module.(3) Stimulating and sensing module developed with high performance MCU STM32F417 was used for controlling other modules, such as EEG acquisition module based on ADS1299, wireless module and LED driving module.(4) Optrode integrated LED and electrode.Finally, we implanted the optrode into the secondary motor cortex of the ChR2 transfected mice to implement three verify experiments.(1) Compared the stimulation effect of laser and this stimulator.(2) Verified the stimulator by the behavior modulation on mice.(3) Confirmed that the closed-loop system was capable of simulating and EEG recording simultaneously. As the results showed, with size of 20 mm×16 mm, weight of 3g, the stimulator could be wirelessly controlled up to 10 meters and provide maximum optical power of 4.5 mW. The stimulator has equal effect to fiber, 30 Hz stimulation enhanced the movement of the mice, which demonstrated that the stimulator was qualified for behavior modulation on mice. The closed-loop system could provide 30 Hz optical stimulation to the mice and record the EEG fluctuated according to the stimulating frequency with 2KSPS sampling rate, which was important for making closed-loop strategy.In conclusion, according to the requirement of neuromodulation on small freely moving animal in vivo, this paper developed a wireless optical stimulator and a closedloop neuromodulation system. Performance tests and experiments on mice showed that both optical devices were competent to activate ion channel, which established a miniaturized optogenetics system for behavior modulation on freely moving animal. This work will help facilitate the application of optogenetics on the study of neural circuit and mechanisms of nerve disease.