Optogenetic Inactivation Modifies Monkey Visuomotor Behavior

Abstract

SUMMARY A critical technique for understanding how neuronal activity contributes to behavior is determining whether perturbing it changes behavior. The advent of optogenetic techniques allows the immediately reversible alteration of neuronal activity in contrast to chemical approaches lasting minutes to hours. Modification of behavior using optogenetics has had substantial success in rodents, but has not been as successful in monkeys. Here we show how optogenetic inactivation of superior colliculus neurons in awake monkeys leads to clear and repeatable behavioral deficits in the metrics of saccadic eye movements. We used our observations to evaluate principles governing the use of optogenetic techniques in the study of the neuronal bases of behavior in monkeys, particularly how experimental design must address relevant parameters, such as the application of light to subcortical structures, the spread of viral injections, and the extent of neuronal inactivation with light.

FEF inactivation with improved optogenetic methods

“…The maximum total light power density applied in this study was 100 mW/mm 2 , similar to what was used in the first electrophysiological demonstrations of optogenetics in the primate (19,61), as well as to what has been used for optogenetic modulation of superficial cortical neurons through a window on the brain (62,63). However, it is much lower than subsequent primate studies that reported behavioral changes using maximal light power densities ranging from several hundred milliwatts per square millimeter to >10 W/mm 2 (11)(12)(13)(14)(15)49).…”

“…A pioneering primate optogenetics study (15) in the superior colliculus noted changes in saccade metrics (latency, velocity, and end points) without behavioral performance changes, implying that these metrics are altered at lower levels of inactivation than are needed to disrupt behavior. Previously, we have not had the means to inactivate with the temporal specificity seen using optogenetics.…”

“…Unfortunately, although optogenetics is widely used to study functional physiology and disease models in rodents and invertebrates, technical challenges have limited the use of optogenetics in the nonhuman primate brain, which has a volume ∼100-fold larger than the rodent brain (10). Pioneering studies in monkeys reported small behavioral effects with excitatory (11)(12)(13)(14) and inhibitory opsins (15)(16)(17). These studies used large light power densities (several hundreds of milliwatts per square meter to 20 W/mm 2 ) but illuminated only small volumes, at most 1 mm 3 , due to both the chosen wavelength and light-delivery method.…”

Optogenetics and Deep Brain Stimulation Neurotechnologies

“…Optogenetics have been used in experimental organisms from C. elegans, zebrafish to mice, primates to analyze neural circuits relevant for many behaviors, from motor behavior (Cavanaugh, Monosov et al 2012) to learning and memory (Liu, Ramirez et al 2012). With the proof of principle demonstration that optogenetics can be safely performed in non-human primates (Han, Qian et al 2009), optogenetics has been explored for its translational potential in treating blindness (Doroudchi, Greenberg et al 2011).…”

Potentiel thérapeutique de la neuromodulation optogénétique

“…Le fait de concentrer ainsi la lumière expose au danger d'induire un échauffement local du parenchyme cérébral à proximité de l'extrémité de la fibre optique [10]. Ainsi, pour la SYNTHÈSE REVUES par des études comportementales [21,30]. Le bénéfice thérapeutique de protocoles utilisant la neuromodulation optogénétique n'a en revanche été évalué que dans un petit nombre de modèles de maladies neurologiques chez le rongeur.…”