Ultrasoft and Highly Stretchable Hydrogel Optical Fibers for In Vivo Optogenetic Modulations

Optogenetics has been widely applied as a cell-specific technique with high temporal resolution for the modulation of neural circuitry in vivo, offering potential novel treatments for neuropsychiatric diseases. However, to date, the most widely used optogenetics waveguides remain silica optical fibers, which may lead to a mismatch in the mechanical properties between the implants and neural tissues. To resolve this issue, alginate-polyacrylamide hydrogel optical fibers can be fabricated in a simplified one-step process, and they show significantly improved characteristics for the in vivo optogenetic applications, including low light-propagation loss and Young's modulus, and high stretchability. After the expression of AAV-CaMKII-ChR2-mCherry, blue light pulses are delivered into hippocampus using a hydrogel-optrode array, and frequency-dependent neural responses can be observed. Moreover, optogenetic stimulation through the chronic implanted hydrogel optical fibers in the primary motor cortex can considerably modulate the animal's behavior. Hydrogel fibers significantly alleviate tissue response at the implant/neural interface, compared with that observed using the silica optical fibers. Taken together, the results of this study demonstrate the feasibility and advantages of the hydrogel optical fiber use for chronic optogenetic modulation in free-moving animals. Hydrogel implant use may allow the development of novel therapeutic strategies for the treatment of neuropsychiatric disorders.