title: Optical Feedback Control and Electrical-Optical Costimulation of Peripheral Nerves.
abstract: BACKGROUND
  Optogenetics is an emerging technology that enables the expression of light-activated ion channels in mammalian cells. Neurons expressing light-activated ion channels can be depolarized using the appropriate wavelength of light. Optical stimulation of neurons could have important implications for further understanding and managing peripheral nerve deficits leading to paresis or paralysis. This study examines the utility of this technology in a feedback-controlled system and the advantages of coupling this technology with conventional electrical stimulation.
  
  
  METHODS
  The sciatic nerves of transgenic mice expressing blue light-activated ion channels (channelrhodopsin-2) were optically manipulated to generate electromyographic responses in the gastrocnemius muscle and to develop two potential applications of this technology: feedback-controlled optical stimulation using a proportional-integral controller, and simultaneous electrical-optical stimulation.
  
  
  RESULTS
  The authors observed repeatable and predictable behavior of the optical controller in over 200 trials and a statistically significant decreased error when using optical feedback control as opposed to non-feedback controlled stimulation (n = 6 limbs). A second application of this technology was the amplification of electrically generated peripheral nerve signals using an optical source. Amplification of electrical activity was observed even when subthreshold electrical stimulation was used.
  
  
  CONCLUSIONS
  Optical feedback control and optical amplification of subthreshold activity extend the versatility of optogenetics in peripheral nerve applications. Optical feedback control is a new application of an approach originally developed for functional electrical stimulation. Optical amplification of subthreshold electrical stimulation motivates future investigations into the optical amplification of endogenous subthreshold peripheral nerve activity (e.g., following spinal cord injury).
authors.affiliation: Madison, Wis.|From the Department of Surgery, Division of Plastic and Reconstructive Surgery, University of Wisconsin School of Medicine and Public Health; and the Department of Biomedical Engineering, University of Wisconsin-Madison.
authors.forename: Sahil K
authors.initials: SK
authors.lastname: Kapur
authors.affiliation: Madison, Wis.|From the Department of Surgery, Division of Plastic and Reconstructive Surgery, University of Wisconsin School of Medicine and Public Health; and the Department of Biomedical Engineering, University of Wisconsin-Madison.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Richner
authors.affiliation: Madison, Wis.|From the Department of Surgery, Division of Plastic and Reconstructive Surgery, University of Wisconsin School of Medicine and Public Health; and the Department of Biomedical Engineering, University of Wisconsin-Madison.
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Brodnick
authors.affiliation: Madison, Wis.|From the Department of Surgery, Division of Plastic and Reconstructive Surgery, University of Wisconsin School of Medicine and Public Health; and the Department of Biomedical Engineering, University of Wisconsin-Madison.
authors.forename: Justin C
authors.initials: JC
authors.lastname: Williams
authors.affiliation: Madison, Wis.|From the Department of Surgery, Division of Plastic and Reconstructive Surgery, University of Wisconsin School of Medicine and Public Health; and the Department of Biomedical Engineering, University of Wisconsin-Madison.
authors.forename: Samuel O
authors.initials: SO
authors.lastname: Poore
mesh_terms: D000818:Animals; D000075402:Channelrhodopsins; D004558:Electric Stimulation; D004576:Electromyography; D025461:Feedback, Physiological / Q000502:physiology*; D006801:Humans; D007473:Ion Channels / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009129:Muscle Tonus / Q000502:physiology; D018482:Muscle, Skeletal / Q000294:innervation*; D009431:Neural Conduction / Q000502:physiology; D009474:Neurons / Q000502:physiology; D062308:Optogenetics / Q000379:methods*; D010525:Peripheral Nerves / Q000502:physiology*; D012584:Sciatic Nerve / Q000502:physiology; D012815:Signal Processing, Computer-Assisted; D012984:Software
chemical_list: D000075402:Channelrhodopsins; D007473:Ion Channels