Optogenetic stimulation of primate V1 reveals local laminar and large-scale cortical networks related to perceptual phosphenes

Abstract

Developing optogenetics in non-human primates (NHPs) is essential for translating its successful implementation in rodents to clinical applications in humans. However, information about how optogenetics influences the primate cortex remains limited. Here, we evaluate how optogenetic stimulation of the primate primary visual cortex (V1) affects local and large-scale network activation concerned with visual perception. To this end we injected an optogenetic construct (AAV9-hSyn-ChR2-eYFP) into the V1 cortex of four macaque monkeys (macaca mulatta) and measured the effects of optogenetic V1 stimulation using functional magnetic resonance imaging (fMRI), laminar electrophysiology, and behavioural assessment. In three macaques, blood-oxygen-dependent (BOLD) fMRI activity could be reliably elicited with optogenetic stimulation in V1 and several connected extrastriate brain areas, including V2/V3, motion-sensitive area MT and the frontal-eye-fields (FEF), in particular when pulsed stimulation at 40 Hz was applied. BOLD modulation was associated with consistent neural spiking activity measured in V1 of two macaques. More detailed analysis revealed strongest neuronal activation in layer 4B and infragranular layers, which tightly reflected the histological expression pattern of the optogenetic construct in V1. Driving this visual network proved sufficient to elicit a visual percept (phosphene) in one macaque during a perceptual choice task. Taken together, our findings reveal the laminar and large-cortical activation pattern related to visual phosphene generation and emphasize the need for further improving optogenetic methods in NHPs as a step towards applications in humans.

Cerebro-cerebellar interactions in nonhuman primates examined by optogenetic functional magnetic resonance imaging

“…2012 ; Ohayon et al. 2013 ; Ortiz-Rios et al. 2021 ), a challenging but promising method for investigating effective connectivity in vivo.…”

“…For example, previous studies showed that optogenetic stimulation of the primary visual cortex (V1) evoked activities only in V1 and the areas directly connected to V1 ( Nakamichi et al. 2019 ; Ortiz-Rios et al. 2021 ).…”

“…Lastly, the pattern of the remote activations may be dependent on the stimulated cortical layer ( Chan et al. 2020 ; Ortiz-Rios et al. 2021 ).…”

Vision Restoration by Optogenetic Therapy and Developments Toward Sonogenetic Therapy

“…Expression of a microbial opsin in the visual cortex was found to activate cortical neurons even in the cortex depth following surface illumination of the brain. 55 – 57 In non-human primates, this cortical activation produced visual saccades toward the corresponding point in the visual field 55 , 56 , 58 and was able to elicit activity in other visual areas as indicated by functional magnetic resonance imaging (fMRI). 58 More subtle changes were described, such as an increased sensitivity to the stimulus orientation, only when the optogenetic stimulation was applied on a column with an orientation selectivity close to that of the stimulus.…”

“… 55 – 57 In non-human primates, this cortical activation produced visual saccades toward the corresponding point in the visual field 55 , 56 , 58 and was able to elicit activity in other visual areas as indicated by functional magnetic resonance imaging (fMRI). 58 More subtle changes were described, such as an increased sensitivity to the stimulus orientation, only when the optogenetic stimulation was applied on a column with an orientation selectivity close to that of the stimulus. 59 , 60 Furthermore, optogenetic activation of single ocular dominance columns generated preferential activation of nearby same-eye columns.…”