Optotagging in primate cortex uncovers excitatory and inhibitory neuron specializations in form vision

Abstract
The perception of complex visual shapes is a hallmark of primates and a foundation for many of their decisions and actions. The neural mechanisms of this visual function are best studied in macaques, but progress in this animal model has been hampered by the inability to dissect the contributions of distinct neuronal cell types. Here, we developed and applied an optogenetic approach for identifying the responses of individual excitatory and inhibitory neurons in the macaque visual cortex with light. Using this optotagging approach in male macaques, we uncovered clear functional differences between the two neuronal cell types. Excitatory and inhibitory neurons showed moderate differences in their extracellular spike waveforms and considerable differences in their visual response properties. Inhibitory neurons signaled simple visual forms almost exclusively, whereas excitatory neurons signaled both simple and complex forms and were more visually responsive than inhibitory neurons. Excitatory neurons had protracted response dynamics and developed their selectivity for complex forms gradually over time. These findings reveal a dominant role for excitatory neurons in visual shape processing, advancing a deeper mechanistic understanding of high-level vision. Beyond these insights, this work establishes a blueprint for elucidating the cell type-specific circuit logic underlying higher brain functions in primates.

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https://www.nature.com/articles/s41467-026-76521-4