Dopamine Neuron-Specific Optogenetic Stimulation in Rhesus Macaques.
Optogenetic studies in mice have revealed new relationships between well-defined neurons and brain functions. However, there are currently no means to achieve the same cell-type specificity in monkeys, which possess an expanded behavioral repertoire and closer anatomical homology to humans. Here, we present a resource for cell-type-specific channelrhodopsin expression in Rhesus monkeys and apply this technique to modulate dopamine activity and monkey choice behavior. These data show that two viral vectors label dopamine neurons with greater than 95% specificity. Infected neurons were activated by light pulses, indicating functional expression. The addition of optical stimulation to reward outcomes promoted the learning of reward-predicting stimuli at the neuronal and behavioral level. Together, these results demonstrate the feasibility of effective and selective stimulation of dopamine neurons in non-human primates and a resource that could be applied to other cell types in the monkey brain.
Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK. Electronic address: wrs@pitt.edu.
William R
WR
Stauffer
Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.
Armin
A
Lak
McGovern Brain Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Aimei
A
Yang
Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.
Melodie
M
Borel
Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.
Ole
O
Paulsen
McGovern Brain Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Edward S
ES
Boyden
Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.
Wolfram
W
Schultz
D000818:Animals; D002755:Choice Behavior / Q000502:physiology*; D000229:Dependovirus / Q000235:genetics; D004298:Dopamine / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000378:metabolism*; D005786:Gene Expression Regulation; D005822:Genetic Vectors / Q000235:genetics; D008253:Macaca mulatta; D062308:Optogenetics / Q000379:methods*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012243:Rhodopsin / Q000235:genetics
D012243:Rhodopsin; D004298:Dopamine