Near-infrared (NIR) optogenetics using up-conversion system

摘要

Non-invasive remote control technologies designed to manipulate neural functions for a comprehensive and quantitative understanding of the neuronal network in the brain as well as for the therapy of neurological disorders have long been awaited. Recently, it has become possible to optically manipulate the neuronal activity using biological photo-reactive molecules such as channelrhodopsin-2 (ChR2). However, ChR2 and its relatives are mostly reactive to visible light which does not effectively penetrate through biological tissues. In contrast, near-infrared (NIR) light penetrates deep into the tissues because biological systems are almost transparent to light within this so-called 'imaging window'. Here we used lanthanide nanoparticles (LNPs), which are composed of rare-earth elements, as luminous bodies to activate channelrhodopsins (ChRs) since they absorb low-energy NIR light to emit high-energy visible light (up-conversion). Neuron-glioma-hybrid ND-7/23 cells were cultured with LNP(NaYF_4:Sc/Yb/Er) particles (peak emission, 543 nm) and transfected to express C1V1 (peak absorbance, 539 nm), a chimera of ChR1 and VChR1. The photocurrents were generated in response to NIR laser light (976 nm) to a level comparable to that evoked by a filtered Hg lamp (530-550 nm). NIR light pulses also evoked action potentials in the cultured neurons that expressed C1V1. It is suggested that the green luminescent light emitted from LNPs effectively activated C1V1 to generate the photocurrent. With the optimization of LNPs, acceptor photo-reactive biomolecules and optics, this system could be applied to non-invasively actuate neurons deep in the brain.