Optogenetic manipulation of the macaque primary visual cortex

Abstract

Globally, about 100 million people suffer from total or severe vision loss and visual prostheses offer the potential to restore some visual function. One key target for visual prosthesis has been the primary visual cortex (V1). Such prostheses typically use electricity to stimulate V1 neurons to artificially induce patterns of spots called phosphenes. Visual prostheses relying on electrical stimulation, however, face challenges such as low visual resolution, lack of activation selectivity, long-term stability due to gliosis and possible painful side effects like headaches. Optogenetics enables the stimulation of neurons using light via lightsensitive ion channels called opsins. Optogenetic stimulation of V1 offers an attractive alternative to electrical stimulation because of its ability to selectively target specific neural populations. Examining the effects of optogenetics in animal models such as nonhuman primates (NHPs) is a vital step before its translation and use in human clinical trials. However, optogenetics use in NHPs has been relatively limited with significant knowledge gaps. In this thesis, I aim to address some of those gaps by studying the effects of optogenetically stimulating the macaque V1. To accomplish this, I first verified the efficacy of V1 optogenetic stimulation and its effect on neural activity recorded by multi-contact laminar probes and characterised the effects of different stimulation parameters. Results showed that light successfully modulated neural activity with the observed effects depending on the light wavelength and stimulation parameters. I followed by examining the effects of stimulation across the different layers of the cortex which revealed very strong modulation of neural activity across the cortical layers as well as stimulation intensity- and frequencyspecific effects. Furthermore, I show similarities between V1 responses to optogenetic responses and the well-established visually evoked responses. ii Finally, I found that with the appropriate testing paradigm, I could confirm that one animal could indeed perceive a phosphene. Not only this, but my paradigm enabled the inference of some of the phosphene’s characteristics. While my results show the challenges of using optogenetics in the macaque brain, they also show its potential. I report that optogenetics can result in neural activity modulation that is sufficient to generate a phosphene opening the way for future studies developing the use of optogenetics for visual prostheses.