Optogenetics is the use of genetically coded, light-gated ion channels or pumps (opsins) for millisecond resolution control of neural activity. By targeting opsin expression to specific cell types and neuronal pathways, optogenetics can expand our understanding of the neural basis of normal and pathological behavior. To maximize the potential of optogenetics to study human cognition and behavior, optogenetics should be applied to the study of nonhuman primates (NHPs). The homology between NHPs and humans makes these animals the best experimental model for understanding human brain function and dysfunction. Moreover, for genetic tools to have translational promise, their use must be demonstrated effectively in large, wild-type animals such as Rhesus macaques. Here, we review recent advances in primate optogenetics. We highlight the technical hurdles that have been cleared, challenges that remain, and summarize how optogenetic experiments are expanding our understanding of primate brain function.

Human and macaque observers can detect and discriminate visual forms defined by differences in texture. The neurophysiological correlates of visual texture perception are not well understood, and have not been studied extensively at the single neuron level in the primate brain. We used a novel family of texture patterns to measure the selectivity of neurons in extrastriate cortical area V2 of the macaque (M. nemestrina, M. fascicularis) for the orientation of texture-defined form, and to distinguish responses to luminance- and texture-defined form. Most V2 cells were selective for the orientation of luminance-defined form; they signaled the orientation of the component gratings that made up the texture patterns but not the overall pattern orientation. In some cells, these luminance responses were modulated by the direction or orientation of the texture envelope, suggesting an interaction of luminance and texture signals. We found little evidence for a “cue-invariant” representation in monkey V2. Few cells showed selectivity for the orientation of texture-defined form; they signaled the orientation of the texture patterns and not that of the component gratings. Small datasets recorded in monkey V1 and cat area 18 showed qualitatively similar patterns of results. Consistent with human functional imaging studies, our findings suggest that signals related to texture-defined form in primate cortex are most salient in areas downstream of V2. V2 may still provide the foundation for texture perception, through the interaction of luminance- and texture-based signals.

The primate brain successfully recognizes objects, even when they are partially occluded. To begin to elucidate the neural substrates of this perceptual capacity, we measured the responses of shape-selective neurons in visual area V4 while monkeys discriminated pairs of shapes under varying degrees of occlusion. We found that neuronal shape selectivity always decreased with increasing occlusion level, with some neurons being notably more robust to occlusion than others. The responses of neurons that maintained their selectivity across a wider range of occlusion levels were often sufficiently sensitive to support behavioral performance. Many of these same neurons were distinctively selective for the curvature of local boundary features and their shape tuning was well fit by a model of boundary curvature (curvature-tuned neurons). A significant subset of V4 neurons also signaled the animal's upcoming behavioral choices; these decision signals had short onset latencies that emerged progressively later for higher occlusion levels. The time course of the decision signals in V4 paralleled that of shape selectivity in curvature-tuned neurons: shape selectivity in curvature-tuned neurons, but not others, emerged earlier than the decision signals. These findings provide evidence for the involvement of contour-based mechanisms in the segmentation and recognition of partially occluded objects, consistent with psychophysical theory. Furthermore, they suggest that area V4 participates in the representation of the relevant sensory signals and the generation of decision signals underlying discrimination.

SUMMARY Purkinje cells of the primate cerebellum play critical but poorly understood roles in the execution of coordinated, accurate movements. Elucidating these roles has been hampered by a lack of techniques for manipulating spiking activity in these cells selectively—a problem common to most cell types in non-transgenic animals. To overcome this obstacle, we constructed AAV vectors carrying the channelrhodopsin-2 (ChR2) gene under the control of a 1 kb L7/Pcp2 promoter. We injected these vectors into the cerebellar cortex of rhesus macaques and tested vector efficacy in three ways. Immunohistochemical analyses confirmed selective ChR2 expression in Purkinje cells. Neurophysiological recordings confirmed robust optogenetic activation. Optical stimulation of the oculomotor vermis caused saccade dysmetria. Our results demonstrate the utility of AAV–L7–ChR2 for revealing the contributions of Purkinje cells to circuit function and behavior, and they attest to the feasibility of promoter-based, targeted, genetic manipulations in primates.

Early experience affects the development of the visual system. Ocular misalignment or unilateral blur often causes amblyopia, a disorder that has become a standard for understanding developmental plasticity. Neurophysiological studies of amblyopia have focused almost entirely on the first stage of cortical processing in striate cortex. Here we provide the first extensive study of how amblyopia affects extrastriate cortex in nonhuman primates. We studied macaque monkeys (Macaca nemestrina) for which we have detailed psychophysical data, directly comparing physiological findings to perceptual capabilities. Because these subjects showed deficits in motion discrimination, we focused on area MT/V5, which plays a central role in motion processing. Most neurons in normal MT respond equally to visual stimuli presented through either eye; most recorded in amblyopes strongly preferred stimulation of the nonamblyopic (fellow) eye. The pooled responses of neurons driven by the amblyopic eye showed reduced sensitivity to coherent motion and preferred higher speeds, in agreement with behavioral measurements. MT neurons were more limited in their capacity to integrate motion information over time than expected from behavioral performance; neurons driven by the amblyopic eye had even shorter integration times than those driven by the fellow eye. We conclude that some, but not all, of the motion sensitivity deficits associated with amblyopia can be explained by abnormal development of MT.