Large Timescale Interrogation of Neuronal Function by Fiberless Optogenetics Using Lanthanide Micro-particles

Toh Miyazaki; Srikanta Chowdhury; Takayuki Yamashita; Takanori Matsubara; Hiromu Yawo; Hideya Yuasa; Akihiro Yamanaka

doi:10.1016/j.celrep.2019.01.001

Large Timescale Interrogation of Neuronal Function by Fiberless Optogenetics Using Lanthanide Micro-particles

Cell Rep. 2019 Jan 22;26(4):1033-1043.e5. doi: 10.1016/j.celrep.2019.01.001.

Authors

Toh Miyazaki¹, Srikanta Chowdhury¹, Takayuki Yamashita², Takanori Matsubara³, Hiromu Yawo⁴, Hideya Yuasa⁵, Akihiro Yamanaka⁶

Affiliations

¹ Department of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, Japan; Department of Neural Regulation, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan; CREST, JST, Honcho Kawaguchi, Saitama 332-0012, Japan.
² Department of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, Japan; Department of Neural Regulation, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan; CREST, JST, Honcho Kawaguchi, Saitama 332-0012, Japan; PRESTO, JST, Honcho Kawaguchi, Saitama 332-0012, Japan.
³ Department of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, Japan; Department of Neural Regulation, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
⁴ Department of Developmental Biology and Neuroscience, Tohoku University Graduate School of Life Sciences, Sendai 980-8577, Japan.
⁵ School of Life Science and Technology, Tokyo Institute of Technology Yokohama 226-8501, Japan.
⁶ Department of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, Japan; Department of Neural Regulation, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan; CREST, JST, Honcho Kawaguchi, Saitama 332-0012, Japan. Electronic address: yamank@riem.nagoya-u.ac.jp.

PMID: 30673599
DOI: 10.1016/j.celrep.2019.01.001

Abstract

Optogenetics requires implantation of light-delivering optical fibers, as current light-sensitive opsins are activated by visible light, which cannot effectively penetrate biological tissues. Insertion of optical fibers and subsequent photostimulation inherently damages brain tissue, and fiber tethering can restrict animal behavior. To overcome these technical limitations, we developed minimally invasive "fiberless" optogenetics using lanthanide micro-particles (LMPs), which emit up-conversion luminescence in the visible spectrum in response to irradiation with tissue-penetrating near-infrared light. Depolarizing (C1V1) and hyperpolarizing (ACR1) opsins were strongly activated by up-conversion luminescence from green-emitting LMPs both in vitro and in vivo. Using this technique, we successfully manipulated locomotive behavior of mice by activating and inhibiting neurons in the dorsal striatum, at a depth of 2 mm from the brain surface. LMPs were retained and remained functional for >8 weeks at the injection site. Fiberless optogenetics offers opportunities to control neuronal function over longer time frames using freely behaving animals.

Keywords: C1V1; Optogenetics; adeno-associated virus vector; anion channelrhodopsin; channelrhodopsin; fiberless; infrared; lanthanide; upconversion.

Publication types

Research Support, Non-U.S. Gov't
Retracted Publication

MeSH terms

Animals
Behavior, Animal / drug effects*
Brain* / metabolism
Brain* / physiopathology
Lanthanoid Series Elements / pharmacology*
Mice
Mice, Transgenic
Opsins / metabolism*
Optic Nerve* / metabolism
Optic Nerve* / physiopathology
Optogenetics*

Substances

Lanthanoid Series Elements
Opsins