Optogenetic control of targeted peripheral axons in freely moving animals

PLoS One. 2013 Aug 21;8(8):e72691. doi: 10.1371/journal.pone.0072691. eCollection 2013.

Abstract

Optogenetic control of the peripheral nervous system (PNS) would enable novel studies of motor control, somatosensory transduction, and pain processing. Such control requires the development of methods to deliver opsins and light to targeted sub-populations of neurons within peripheral nerves. We report here methods to deliver opsins and light to targeted peripheral neurons and robust optogenetic modulation of motor neuron activity in freely moving, non-transgenic mammals. We show that intramuscular injection of adeno-associated virus serotype 6 enables expression of channelrhodopsin (ChR2) in motor neurons innervating the injected muscle. Illumination of nerves containing mixed populations of axons from these targeted neurons and from neurons innervating other muscles produces ChR2-mediated optogenetic activation restricted to the injected muscle. We demonstrate that an implanted optical nerve cuff is well-tolerated, delivers light to the sciatic nerve, and optically stimulates muscle in freely moving rats. These methods can be broadly applied to study PNS disorders and lay the groundwork for future therapeutic application of optogenetics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Axons*
  • Channelrhodopsins
  • Female
  • Motor Neurons / physiology
  • Optogenetics*
  • Peripheral Nerves / physiology*
  • Rats
  • Rats, Inbred F344

Substances

  • Channelrhodopsins

Grant support

This study was supported by the Stanford Bio-X Program (SLD and KD). CT was supported by a Swiss National Science Foundation Fellowship. SMI was supported by an Office of Technology Licensing Stanford Graduate Fellowship. KLM was supported by a Bio-X Bioengineering Graduate Fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.