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.
Highlights
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’[16]
When a C1V1-expressing ND7/23 cell was irradiated with filtered green light of a Hg lamp (530–550 nm; 14 mW/mm2), an almost maximal inward photocurrent was generated with a peak and plateau at a holding potential of − 60 mV (Fig. 2C)
In the present study we provide evidence that the NIR light could be applied for the optogenetic manipulation of neural activities when lanthanide nanoparticles (LNPs) are used as donors and ChRs as acceptors
Summary
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’[16]. ChRs responsive to red light have been obtained through gene mining or molecular modifications[17,18]. Neurons deep in the mouse brain were activated by red light even through skin and skull when they expressed ReaChR, a variant C1V1 which is a chimera of ChR1 and one of Volvox carteri-derived ChRs (VChR1). No biological molecules known at present are optimized to absorb NIR light. We have the idea of using lanthanide nanoparticles (LNPs), composed of rare-earth elements, as luminous bodies to activate ChRs since they absorb low-energy photons of NIR light to emit high-energy photons of visible light (up-conversion)[19]. A preliminary report of this research has been published elsewhere[20]
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