Near-infrared (NIR) up-conversion optogenetics

TLDR

Non‑invasive remote control of neural activity has long been sought, but conventional optogenetics using channelrhodopsin‑2 relies on visible light that poorly penetrates tissue, whereas near‑infrared light (650–1450 nm) can reach deep brain regions. The study aims to develop a novel optogenetic platform that couples lanthanide nanoparticles with channelrhodopsins to enable deep‑tissue neural control using near‑infrared light. Lanthanide nanoparticles absorb NIR light and up‑convert it to visible photons that activate nearby channelrhodopsins when irradiated with an NIR laser.

Abstract

Abstract Non-invasive remote control technologies designed to manipulate neural functions have been long-awaited for the comprehensive and quantitative understanding of neuronal network in the brain as well as for the therapy of neurological disorders. Recently, it has become possible for the neuronal activity to be optically manipulated using biological photo-reactive molecules such as channelrhodopsin (ChR)-2. 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 (650–1450 nm) 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), composed of rare-earth elements, as luminous bodies to activate ChRs since they absorb low-energy NIR light to emit high-energy visible light (up-conversion). Here, we created a new type of optogenetic system which consists of the donor LNPs and the acceptor ChRs. The NIR laser irradiation emitted visible light from LNPs, then induced the photo-reactive responses in the near-by cells that expressed ChRs. However, there remains room for large improvements in the energy efficiency of the LNP-ChR system.