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.

Keywords: monkey; optogenetics; primate.

Fig. 1.

Histological sections showing AAV vector-mediated opsin expression in the macaque cerebellar (A) and cerebral cortices (B–D). The vector constructs injected are listed in the title of each panel (minP, minimal promoter; PV, parvalbumin). Each section was processed using antibodies recognizing the fluorescent reporter encoded by the vector (red) and a marker gene for the targeted cell type (green) and counterstained with DAPI (blue). The primary antibodies were as follows: (A) mouse mCherry (Clontech 632543) and rabbit calbindin (Swant CB38), (B and C) rabbit mCherry (GeneTex GTX59788) and mouse parvalbumin (PV Swant 235), (D) chicken GFP (Abcam 13970-1000) and mouse parvalbumin (PV Swant 235).