Optogenetic and Electrical Microstimulation Systematically Bias Visuospatial Choice in Primates

Dai, Ji; Brooks, Daniel I.; Sheinberg, David L.

doi:10.1016/j.cub.2013.11.011

Cited by 93 publications

(116 citation statements)

References 32 publications

Supporting

Mentioning

113

Contrasting

Order By: Relevance

“…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).…”

Section: Significancementioning

confidence: 57%

“…Bundles of fibers illuminate larger volumes, but the increased penetration diameter leads to greater tissue and vascular damage, because the damage is proportional to fiber diameter (19,(44)(45)(46)(47)(48). Tapered glass fibers reduce penetration damage, but narrowly focus light to tiny illumination areas (<100 μm 2 ) (13,49). Here, a 250-μm-diameter plastic optical fiber was tapered to a 70-to 100-μm diameter over a 3-to 5-mm-long tip ( Fig.…”

Section: Significancementioning

confidence: 99%

“…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.…”

mentioning

confidence: 99%

See 2 more Smart Citations

FEF inactivation with improved optogenetic methods

Acker

Pino

Boyden

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

102

114

View full text Add to dashboard Cite

Optogenetic methods have been highly effective for suppressing neural activity and modulating behavior in rodents, but effects have been much smaller in primates, which have much larger brains. Here, we present a suite of technologies to use optogenetics effectively in primates and apply these tools to a classic question in oculomotor control. First, we measured light absorption and heat propagation in vivo, optimized the conditions for using the red-light-shifted halorhodopsin Jaws in primates, and developed a large-volume illuminator to maximize light delivery with minimal heating and tissue displacement. Together, these advances allowed for nearly universal neuronal inactivation across more than 10 mm 3 of the cortex. Using these tools, we demonstrated large behavioral changes (i.e., up to several fold increases in error rate) with relatively low light power densities (≤100 mW/mm 2 ) in the frontal eye field (FEF). Pharmacological inactivation studies have shown that the FEF is critical for executing saccades to remembered locations. FEF neurons increase their firing rate during the three epochs of the memory-guided saccade task: visual stimulus presentation, the delay interval, and motor preparation. It is unclear from earlier work, however, whether FEF activity during each epoch is necessary for memory-guided saccade execution. By harnessing the temporal specificity of optogenetics, we found that FEF contributes to memory-guided eye movements during every epoch of the memory-guided saccade task (the visual, delay, and motor periods).primate | optogenetics | FEF | Jaws | memory-guided saccade T he frontal eye field (FEF) is an important brain area for making saccades to remembered locations. FEF neurons increase their firing rate during three epochs of memory-guided saccades: (i) target presentation, (ii) delay period, and (iii) motor preparation. Pharmacological inactivation of the FEF impairs memory-guided saccades (1-7), but because pharmacological inactivation inhibits all FEF neuronal activity, it is unclear if the FEF's role is specific to one or more task epochs (8,9). By selectively inactivating the FEF during each task epoch, we can determine whether visual-, delay-, or motor-related firing (or some combination of the three types of firing) contributes to memory-guided saccades.The ideal tool for this study is optogenetics, which allows for millisecond-precise, light-driven neuronal control. 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 (11-14) and inhibitory opsins (15-17). 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-deliver...

show abstract

Section: Significancementioning

confidence: 57%

Section: Significancementioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

FEF inactivation with improved optogenetic methods

Acker

Pino

Boyden

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

102

114

View full text Add to dashboard Cite

show abstract

“…The same study found that local electrical stimulation produced multisynaptic modulation on dopamine release and this effect was absent in selective optogenetic stimulation [112]. Furthermore, Dai et al [113] directly compared optogenetics and electrical stimulation in rhesus monkeys and demonstrated that both stimulation approaches produced a similar response in a lateral visuospatial discrimination task while stimulating the intraparietal area.…”

Section: Benefits Of Optogeneticsmentioning

confidence: 95%

Optogenetic Approaches to Target Specific Neural Circuits in Post-stroke Recovery

2016

View full text Add to dashboard Cite

Stroke is a leading cause of death and disability in the USA, yet treatment options are very limited. Functional recovery can occur after stroke and is attributed, in part, to rewiring of neural connections in areas adjacent to or remotely connected to the infarct. A better understanding of neural circuit rewiring is thus an important step toward developing future therapeutic strategies for stroke recovery. Because stroke disrupts functional connections in peri-infarct and remotely connected regions, it is important to investigate brain-wide network dynamics during post-stroke recovery. Optogenetics is a revolutionary neuroscience tool that uses bioengineered lightsensitive proteins to selectively activate or inhibit specific cell types and neural circuits within milliseconds, allowing greater specificity and temporal precision for dissecting neural circuit mechanisms in diseases. In this review, we discuss the current view of post-stroke remapping and recovery, including recent studies that use optogenetics to investigate neural circuit remapping after stroke, as well as optogenetic stimulation to enhance stroke recovery. Multimodal approaches employing optogenetics in conjunction with other readouts (e.g., in vivo neuroimaging techniques, behavior assays, and next-generation sequencing) will advance our understanding of neural circuit reorganization during post-stroke recovery, as well as provide important insights into which brain circuits to target when designing brain stimulation strategies for future clinical studies.

show abstract

“…Puncture a hole in the center of the square using a 26 gauge needle. 4. Remove the large screw on cap from the integrating sphere and cover the opening with the diaphragm.…”

Section: Illuminator Calibration and Quality Controlmentioning

confidence: 99%

Large Volume, Behaviorally-relevant Illumination for Optogenetics in Non-human Primates

Acker

Pino

Boyden

et al. 2017

JoVE

View full text Add to dashboard Cite

This protocol describes a large-volume illuminator, which was developed for optogenetic manipulations in the non-human primate brain. The illuminator is a modified plastic optical fiber with etched tip, such that the light emitting surface area is > 100x that of a conventional fiber. In addition to describing the construction of the large-volume illuminator, this protocol details the quality-control calibration used to ensure even light distribution. Further, this protocol describes techniques for inserting and removing the large volume illuminator. Both superficial and deep structures may be illuminated. This large volume illuminator does not need to be physically coupled to an electrode, and because the illuminator is made of plastic, not glass, it will simply bend in circumstances when traditional optical fibers would shatter. Because this illuminator delivers light over behaviorally-relevant tissue volumes (≈ 10 mm 3 ) with no greater penetration damage than a conventional optical fiber, it facilitates behavioral studies using optogenetics in non-human primates.

show abstract

Optogenetic and Electrical Microstimulation Systematically Bias Visuospatial Choice in Primates

Cited by 93 publications

References 32 publications

FEF inactivation with improved optogenetic methods

FEF inactivation with improved optogenetic methods

Optogenetic Approaches to Target Specific Neural Circuits in Post-stroke Recovery

Large Volume, Behaviorally-relevant Illumination for Optogenetics in Non-human Primates

Contact Info

Product

Resources

About