An optogenetic toolbox designed for primates

Diester, Ilka; Kaufman, Matthew T.; Mogri, Murtaza; Pashaie, Ramin; Goo, Werapong; Yizhar, Ofer; Ramakrishnan, Charu; Deisseroth, Karl; Shenoy, Krishna V.

doi:10.1038/nn.2749

Cited by 407 publications

(424 citation statements)

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“…2). Previous optogenetic inactivation studies focusing on related brain areas have interpreted a lack of effect of transient inactivation as a lack of role in behavior 13,42 . Our results imply that redundancy across a distributed network could mask possible causal roles in optogenetics experiments.…”

Section: Discussionmentioning

confidence: 99%

Robust neuronal dynamics in premotor cortex during motor planning

Li¹,

Daie²,

Svoboda³

et al. 2016

Nature

461

485

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Neural activity maintains representations that bridge past and future events, often over many seconds. Network models can produce persistent and ramping activity, but the positive feedback that is critical for these slow dynamics can cause sensitivity to perturbations. Here we use electrophysiology and optogenetic perturbations in mouse premotor cortex to probe robustness of persistent neural representations during motor planning. Preparatory activity is remarkably robust to large-scale unilateral silencing: detailed neural dynamics that drive specific future movements were quickly and selectively restored by the network. Selectivity did not recover after bilateral silencing of premotor cortex. Perturbations to one hemisphere are thus corrected by information from the other hemisphere. Corpus callosum bisections demonstrated that premotor cortex hemispheres can maintain preparatory activity independently. Redundancy across selectively coupled modules, as we observed in premotor cortex, is a hallmark of robust control systems. Network models incorporating these principles show robustness that is consistent with data.

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Section: Discussionmentioning

confidence: 99%

Robust neuronal dynamics in premotor cortex during motor planning

Li¹,

Daie²,

Svoboda³

et al. 2016

Nature

461

485

View full text Add to dashboard Cite

show abstract

“…In contrast, FEF pharmacological inactivation studies report inactivation of volumes of ∼10 mm 3 (2, 3). Further, optogenetically driven neuronal effects in primates are often heterogeneous, decreasing the activity of some neurons and increasing the activity of others (14,(17)(18)(19). No primate optogenetics study has reported inactivation levels near the levels of FEF pharmacological inactivation studies, namely, >80% reduction in firing rate relative to baseline reported in >80% of neurons (1-3).…”

mentioning

confidence: 99%

FEF inactivation with improved optogenetic methods

Acker

Pino

Boyden

et al. 2016

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

104

114

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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...

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“…However, optogenetics has provided methods to transiently, delicately, and reversibly turn molecularly identified neuronal cell types or even just their connections off and on again for time-scales lasting from milliseconds to hours. Although such invasive techniques are off-limits in humans, they are being routinely implemented in mice [5,6] and, to a much more limited extent, in monkeys [7][8][9].…”

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confidence: 99%

Top-down attention and consciousness: comment on Cohen et al.

Tsuchiya¹,

Block²,

Koch³

2012

Trends in Cognitive Sciences

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Cohen and colleagues masterfully summarize the psychophysical and neurophysiological evidence pertaining to the distinction between visual attention and visual consciousness, concluding that attention is necessary but not sufficient for consciousness [1]. We disagree with their view for the following reasons.In our own work, we have been cautious to claim only that one can become conscious of an attribute of some class of objects in the near absence of top-down, endogenous attentional amplification [2,3]. Given the close relationship between stimulus strength and bottom-up, exogenous attention, we do not think it is possible to dissociate bottomup attention from consciousness.To our mind, the function of both forms of attention is to resolve ambiguity due to large, overlapping receptive fields and the presence of competing objects within cluttered natural scenes. The brain accomplishes this mainly by amplifying the neuronal representation of the attended attribute at the expense of unattended stimuli. These topdown attentional signals originate in frontal and parietal cortical regions, and feed back into earlier sensory corticothalamic stages of processing. However, for detection or coarse discrimination of an isolated object, top-down attention does not play a significant role [4]. There is no computational reason and no evidence for the claim that top-down attention is required to become conscious of simple, isolated objects, such as a single oriented bar.With psychophysical manipulation alone, diffuse topdown attention to a stimulus cannot be excluded. However, optogenetics has provided methods to transiently, delicately, and reversibly turn molecularly identified neuronal cell types or even just their connections off and on again for time-scales lasting from milliseconds to hours. Although such invasive techniques are off-limits in humans, they are being routinely implemented in mice [5,6] and, to a much more limited extent, in monkeys [7][8][9].In the next few years, it will become possible to reversibly turn off feedback from higher cortical regions to visual cortex, without interfering with the forward flow of information. We would argue that under these conditions, top-down attention will have been effectively locked out of visual cortex. It will then become possible to address the question of whether the animals can still respond in a behaviorally meaningful manner to such a non-attended stimulus. Such experiments require sophisticated behavioral controls and very selective molecular tools, as well as large-scale observatories to record the activity of large numbers of genetically identified cell types. This is the aim of the ongoing project MindScope at the Allen Institute for Brain Science [10].Lastly, the authors are overly restrictive in their supposition that, if any one of four distinct ways of withdrawing attention can eliminate conscious perception, then consciousness requires attention. None of these four tasks are 'pure' attentional manipulations: they change processing in a variety of ways, d...

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An optogenetic toolbox designed for primates

Cited by 407 publications

References 50 publications

Robust neuronal dynamics in premotor cortex during motor planning

Robust neuronal dynamics in premotor cortex during motor planning

FEF inactivation with improved optogenetic methods

Top-down attention and consciousness: comment on Cohen et al.

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