Journal of Neurophysiology

Optogenetics through windows on the brain in the nonhuman primate

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

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 C. Elegans is now well established. However, application of this technology in non-human primates (NHP) 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, non-invasive 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.

  • primate optogenetics
  • artificial dura
  • optical imaging
  • in-vivo epifluorescence
  • electrophysiology