Journal Article

An optogenetic toolbox designed for primates

Goo, Werapong, Yizhar, Ofer, Deisseroth, Karl, Shenoy, Krishna V, Diester, Ilka, Mogri, Murtaza, Pashaie, Ramin, Kaufman, Matthew T, Ramakrishnan, Charu

2011

Overview

Here the authors describe a set of new optogenetic tools for use in primates that are meant to address the unique constraints of working with this species. They characterize opsin expression, the reliability of optogenetic stimulation and its effect on behavior, and methods for determining localization and expression levels prior to the completion of experiments. Optogenetics is a technique for controlling subpopulations of neurons in the intact brain using light. This technique has the potential to enhance basic systems neuroscience research and to inform the mechanisms and treatment of brain injury and disease. Before launching large-scale primate studies, the method needs to be further characterized and adapted for use in the primate brain. We assessed the safety and efficiency of two viral vector systems (lentivirus and adeno-associated virus), two human promoters (human synapsin ( hSyn ) and human thymocyte-1 ( hThy-1 )) and three excitatory and inhibitory mammalian codon-optimized opsins (channelrhodopsin-2, enhanced Natronomonas pharaonis halorhodopsin and the step-function opsin), which we characterized electrophysiologically, histologically and behaviorally in rhesus monkeys ( Macaca mulatta ). We also introduced a new device for measuring in vivo fluorescence over time, allowing minimally invasive assessment of construct expression in the intact brain. We present a set of optogenetic tools designed for optogenetic experiments in the non-human primate brain.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 631/1647/2253 / 631/378 / 631/378/557 / Analysis / Animal Genetics and Genomics / Animals / Behavior / Behavioral Sciences / Biological Techniques / Biomedical and Life Sciences / Biomedicine / Brain stimulation / Computer engineering / Dependovirus - genetics / Dependovirus - metabolism / Electrical engineering / Experiments / Gene Transfer Techniques / Genetic aspects / Genetic Vectors - genetics / Genetic Vectors - metabolism / Humans / Lentivirus - genetics / Lentivirus - metabolism / Light / Macaca mulatta - anatomy & histology / Macaca mulatta - genetics / Macaca mulatta - physiology / Monkeys & apes / Motor cortex / Neurobiology / Neurons / Neurosciences / Opsins / Opsins - genetics / Opsins - metabolism / Photic Stimulation - methods / Physiological aspects / Primates / Primates - anatomy & histology / Primates - genetics / Primates - physiology / Promoter Regions, Genetic / Recombinant Fusion Proteins - genetics / Recombinant Fusion Proteins - metabolism / Synapsins - genetics / Synapsins - metabolism / technical-report / Vectors (Biology)