Light distribution and thermal effects in the rat brain under optogenetic stimulation

Gysbrechts, Barbara; Wang, Ling; Trong, Nghia Nguyen Do; Cabral, Henrique; Navratilova, Zaneta; Battaglia, Francesco P.; Saeys, Wouter; Bartic, Carmen

doi:10.1002/jbio.201500106

Cited by 38 publications

(39 citation statements)

References 36 publications

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“…Regarding MC simulations, strong limitations also arise from the enormous simulation times associated with complex voxelized heterogeneous geometries24 and lack of validated optical properties measured in vivo , despite on-going efforts2526. In this context, our experimental light distribution measurements reveal that the extent of light distribution relative to the fiber is larger in the lateral than axial axis, which is not reported in the vast literature of analytical calculations or Monte Carlo simulations of fiber guided light in cerebral tissue212327. Although the fiber output is an extended source and not a point source, this result was unexpected, considering the high forward diffusion anisotropy of brain tissue.…”

Section: Discussionmentioning

confidence: 86%

Experimental assessment of the safety and potential efficacy of high irradiance photostimulation of brain tissues

Senova¹,

Scisniak²,

Chiang³

et al. 2017

Sci Rep

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Optogenetics is widely used in fundamental neuroscience. Its potential clinical translation for brain neuromodulation requires a careful assessment of the safety and efficacy of repeated, sustained optical stimulation of large volumes of brain tissues. This study was performed in rats and not in non-human primates for ethical reasons. We studied the spatial distribution of light, potential damage, and non-physiological effects in vivo, in anesthetized rat brains, on large brain volumes, following repeated high irradiance photo-stimulation. We generated 2D irradiance and temperature increase surface maps based on recordings taken during optical stimulation using irradiance and temporal parameters representative of common optogenetics experiments. Irradiances of 100 to 600 mW/mm2 with 5 ms pulses at 20, 40, and 60 Hz were applied during 90 s. In vivo electrophysiological recordings and post-mortem histological analyses showed that high power light stimulation had no obvious phototoxic effects and did not trigger non-physiological functional activation. This study demonstrates the ability to illuminate cortical layers to a depth of several millimeters using pulsed red light without detrimental thermal damages.

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Section: Discussionmentioning

confidence: 86%

Experimental assessment of the safety and potential efficacy of high irradiance photostimulation of brain tissues

Senova¹,

Scisniak²,

Chiang³

et al. 2017

Sci Rep

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“…To compare visible light wavelengths accurately, and thus select the optimal opsin for our studies, we developed techniques to measure visible light propagation omnidirectionally in vivo. Previous optogenetic studies have used visible light propagation measurements and tissue properties derived from in vitro or ex vivo specimens (26)(27)(28)(29)(30)(31)(32). For example, Azimipour et al (33) recently published an atlas of optical properties and predicted light distribution in rat brain tissue.…”

Section: Significancementioning

confidence: 99%

“…Their model was later updated to include information about blood vessels (34), yet all of the data in both reports were derived from 0.5-mm-thick ex vivo slices rather than the intact living brain. Gysbrechts et al (32) similarly sought to ascertain optical properties of fresh rat brain tissue bathed in cold saline, which also contained deoxygenated hemoglobin and likely diluted the blood present in the sample. Gysbrechts et al (32) used these optical measurements to estimate light-induced thermal effects, but did not validate their estimates with in vivo measurements.…”

Section: Significancementioning

confidence: 99%

“…Gysbrechts et al (32) similarly sought to ascertain optical properties of fresh rat brain tissue bathed in cold saline, which also contained deoxygenated hemoglobin and likely diluted the blood present in the sample. Gysbrechts et al (32) used these optical measurements to estimate light-induced thermal effects, but did not validate their estimates with in vivo measurements. Stujenske et al (35) performed temperature measurements in vivo to ascertain the effects of green light on neural tissue and found that the temperature increases predicted by models were higher than measured in vivo, underscoring the importance of in vivo measurements.…”

Section: Significancementioning

confidence: 99%

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FEF inactivation with improved optogenetic methods

Acker

Pino

Boyden

et al. 2016

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

102

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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“…Targeted illumination with a temporal precision of the order of milliseconds and the spatial precision of few tens of micrometers is a necessity for certain studies such as neuronal signalling11011. Non-targeted illumination is also known to generate abrupt heat effects in regions of non-interests in many studies, hindering their research studies61213. This elucidates the importance of targeted illumination system with an improved spatial and temporal resolution.…”

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confidence: 99%

A targeted illumination optical fiber probe for high resolution fluorescence imaging and optical switching

Shinde

Perinchery

Murukeshan

2017

Sci Rep

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An optical imaging probe with targeted multispectral and spatiotemporal illumination features has applications in many diagnostic biomedical studies. However, these systems are mostly adapted in conventional microscopes, limiting their use for in vitro applications. We present a variable resolution imaging probe using a digital micromirror device (DMD) with an achievable maximum lateral resolution of 2.7 μm and an axial resolution of 5.5 μm, along with precise shape selective targeted illumination ability. We have demonstrated switching of different wavelengths to image multiple regions in the field of view. Moreover, the targeted illumination feature allows enhanced image contrast by time averaged imaging of selected regions with different optical exposure. The region specific multidirectional scanning feature of this probe has facilitated high speed targeted confocal imaging.

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Light distribution and thermal effects in the rat brain under optogenetic stimulation

Cited by 38 publications

References 36 publications

Experimental assessment of the safety and potential efficacy of high irradiance photostimulation of brain tissues

Experimental assessment of the safety and potential efficacy of high irradiance photostimulation of brain tissues

FEF inactivation with improved optogenetic methods

A targeted illumination optical fiber probe for high resolution fluorescence imaging and optical switching

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