RT Journal Article SR Electronic T1 Interfacing with Neural Activity via Femtosecond Laser Stimulation of Drug-Encapsulating Liposomal Nanostructures JF eneuro JO eNeuro FD Society for Neuroscience SP ENEURO.0107-16.2016 DO 10.1523/ENEURO.0107-16.2016 VO 3 IS 6 A1 Takashi Nakano A1 Sean M. Mackay A1 Eng Wui Tan A1 Keshav M. Dani A1 Jeff Wickens YR 2016 UL http://www.eneuro.org/content/3/6/ENEURO.0107-16.2016.abstract AB External control over rapid and precise release of chemicals in the brain potentially provides a powerful interface with neural activity. Optical manipulation techniques, such as optogenetics and caged compounds, enable remote control of neural activity and behavior with fine spatiotemporal resolution. However, these methods are limited to chemicals that are naturally present in the brain or chemically suitable for caging. Here, we demonstrate the ability to interface with neural functioning via a wide range of neurochemicals released by stimulating loaded liposomal nanostructures with femtosecond lasers. Using a commercial two-photon microscope, we released inhibitory or excitatory neurochemicals to evoke subthreshold and suprathreshold changes in membrane potential in a live mouse brain slice. The responses were repeatable and could be controlled by adjusting laser stimulation characteristics. We also demonstrate the release of a wider range of chemicals—which previously were impossible to release by optogenetics or uncaging—including synthetic analogs of naturally occurring neurochemicals. In particular, we demonstrate the release of a synthetic receptor-specific agonist that exerts physiological effects on long-term synaptic plasticity. Further, we show that the loaded liposomal nanostructures remain functional for weeks in a live mouse. In conclusion, we demonstrate new techniques capable of interfacing with live neurons, and extendable to in vivo applications.