| 其他摘要 | 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 460nm
uLED 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, 30Hz
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 30Hz 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. |
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