Primate optogenetics: Progress and prognosis

Abstract

Monkeys are a premier model organism for neuroscience research. Activity in the central nervous systems of monkeys can be recorded and manipulated while they perform complex perceptual, motor, or cognitive tasks. Conventional techniques for manipulating neural activity in monkeys are too coarse to address many of the outstanding questions in primate neuroscience, but optogenetics holds the promise to overcome this hurdle. In this article, we review the progress that has been made in primate optogenetics over the past 5 years. We emphasize the use of gene regulatory sequences in viral vectors to target specific neuronal types, and we present data on vectors that we engineered to target parvalbumin-expressing neurons. We conclude with a discussion of the utility of optogenetics for treating sensorimotor hearing loss and Parkinson’s disease, areas of translational neuroscience in which monkeys provide unique leverage for basic science and medicine.

Alzheimer’s-like pathology in aging rhesus macaques: Unique opportunity to study the etiology and treatment of Alzheimer’s disease

“…Genetic tools in monkeys have lagged far behind those in mice, but are at last are having success [see El-Shamayleh and Horwitz (90)]. Thus, we are now positioned to learn how a genetic alteration that increases risk for LOAD alters molecular events in the aging association cortex to exacerbate pathology.…”

Chronically implantable LED arrays for behavioral optogenetics in primates

“…Indeed, only a handful of studies in NHPs show behavioral effects of optogenetic perturbation, across sensory, motor, and cognitive domains despite tremendous interests [3][4][5][6][7][8][9][10] . The dearth of documented behavioral impacts using optogenetics may stem from several problems, including difficulties of successful genetic targeting of neurons and of delivering sufficient light to perturb those neurons in the primate brain.…”

The Memory-Modifying Potential of Optogenetics and the Need for Neuroethics

“…Another disease awaiting the approval of initial clinical trials involving the application of optogenetic therapy and for which existing methods of treatment show limited effectiveness is urinary bladder syndrome [5]. Furthermore, many optogenetic studies conducted on animal models, such as rodents or nonhuman primates [6], were designed with the explicit goal of developing better targeted brain stimulation treatments for various psychiatric and neurological disorders in humans [7][8][9][10][11][12][13][14]. These attempts, along with rapid advancements in the field, demonstrate that optogenetics is already progressing towards clinical application.…”

“…Two leading authors of this research were invited to give a TED talk: https://www.ted.com/talks/steve_ramirez_and_xu_liu_a_mouse_a_ laser_beam_a_manipulated_memory?language=en6 Regions known to encode a specific memory trace, or memory engrams, which are reactivated upon retrieval 7. The "Lost in the Mall" technique is a memory implantation method developed by Elizabeth Loftus and Jim Coan in order to show the ease with which one can manipulate human memory through suggestions about events that never actually took place.…”