Optogenetics through windows on the brain in the nonhuman primate

Octavio Ruiz, Brian R. Lustig, Jonathan J. Nassi, Ali Cetin, John H. Reynolds, Thomas D. Albright, Edward M. Callaway, Gene R. Stoner, Anna W. Roe

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

Optogenetics combines optics and genetics to control neuronal activity with cell-type specificity and millisecond temporal precision. Its use in model organisms such as rodents, Drosophila, and Caenorhabditis elegans is now well-established. However, application of this technology in nonhuman primates (NHPs) has been slow to develop. One key challenge has been the delivery of viruses and light to the brain through the thick dura mater of NHPs, which can only be penetrated with large-diameter devices that damage the brain. The opacity of the NHP dura prevents visualization of the underlying cortex, limiting the spatial precision of virus injections, electrophysiological recordings, and photostimulation. Here, we describe a new optogenetics approach in which the native dura is replaced with an optically transparent artificial dura. This artificial dura can be penetrated with fine glass micropipettes, enabling precisely targeted injections of virus into brain tissue with minimal damage to cortex. The expression of optogenetic agents can be monitored visually over time. Most critically, this optical window permits targeted, noninvasive photostimulation and concomitant measurements of neuronal activity via intrinsic signal imaging and electrophysiological recordings. We present results from both anesthetized-paralyzed (optical imaging) and awake-behaving NHPs (electrophysiology). The improvements over current methods made possible by the artificial dura should enable the widespread use of optogenetic tools in NHP research, a key step toward the development of therapies for neuropsychiatric and neurological diseases in humans.

Original languageEnglish (US)
Pages (from-to)1455-1467
Number of pages13
JournalJournal of neurophysiology
Volume110
Issue number6
DOIs
StatePublished - Sep 15 2013

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Keywords

  • Artificial dura
  • Electrophysiology
  • In vivo epifluorescence
  • Optical imaging
  • Primate optogenetics

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology

Cite this

Ruiz, O., Lustig, B. R., Nassi, J. J., Cetin, A., Reynolds, J. H., Albright, T. D., Callaway, E. M., Stoner, G. R., & Roe, A. W. (2013). Optogenetics through windows on the brain in the nonhuman primate. Journal of neurophysiology, 110(6), 1455-1467. https://doi.org/10.1152/jn.00153.2013