All-optical stimulation and imaging in macaque V1 reveals neural and behavioral masking effects of optogenetic stimulation in a threshold detection task

Electrophysiological recording and electrical micro-stimulation in the visual cortex of behaving primates has provided a wealth of knowledge about how neural activity is related to behavioral decisions. Recent advances in optogenetics are opening new possibilities for recording and modifying neural activity in behaving primates. Using viral vectors, we co-expressed a red-shited microbial opsin (C1V1) and a calcium indicator (GCaM6f) in excitatory neurons in macaque V1. Using widefield imaging, we measured robust GCaMP6f neural responses to both normal visual and direct optical stimulation (optostim) at low (0.6 mW/mm2) light levels. We further found that optostim and visually-evoked activity interact in a sublinear way. Specifically, optostim reduced the magnitude of the visually-evoked neural response and reduced the monkey’s behavioral sensitivity in a Go/No-Go visual detection task. A monkey was trained to detect a small Gaussian target presented at the retinotopic location corresponding to the C1V1/GCaMP co-expression site (~ 1.5° eccentricity). The monkey reported target present with a saccade to the target. Under purely visual stimulation, the monkey’s contrast detection threshold was 5%. In separate blocks, with 0.6 mW/mm2 optostim, the detection threshold between optostim-blank and optostim-plus-target trials was 8%. With optostim, V1 neural response representing the target reduced by 33% (±10% sem) after accounting for the optostim component. Doubling the optostim intensity further increased the threshold and reduced the neural signal. By contrast, when the target was placed ~1° away at retinotopic location corresponding to a V1 site expressing only GCaMP6f (no opsin), we found no optostim driven behavioral or neural effects on target detectability. In conclusion, our results represent a first step toward an all-optical platform for manipulating population activity in behaving macaques and studying the effect of these manipulations on visual processing and behavior.