Modeling the Spatiotemporal Dynamics of Light and Heat Propagation for In Vivo Optogenetics

Stujenske, Joseph M.; Spellman, Timothy; Gordon, Joshua A.

doi:10.1016/j.celrep.2015.06.036

Cited by 337 publications

(404 citation statements)

References 41 publications

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“…Most of these data have considered solely the excitation in the blue-green range [23,48] in the rodent brain. In a previous work, we studied exper imentally in vivo in rodents the minimally invasive photostimulation using a fiber (0.4 mm diameter and a 0.48 NA) with 5 ms pulses of 638 nm light with a power varying from 100 to 600 mW mm −2 and a frequency varying from 20 to 60 Hz [49]. We observed a maximum temperature rise of about 0.1 °C to 2.5 °C depending on the experimental parameters.…”

Section: What Is the Expected Temperature Rise And How May It Affectmentioning

confidence: 99%

Optical and thermal simulations for the design of optodes for minimally invasive optogenetics stimulation or photomodulation of deep and large cortical areas in non-human primate brain

et al. 2018

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The use of optogenetics or photobiomodulation in non-human primate (NHP) requires the ability to noninvasively stimulate large and deep cortical brain tissues volumes. In this context, the optical and geometrical parameters of optodes are critical. Methods and general guidelines to optimize these parameters have to be defined. Objective. We propose the design of an optode for safe and efficient optical stimulation of a large volume of NHP cortex, down to 3-5 mm depths without inserting fibers into the cortex. Approach. Monte Carlo simulations of optical and thermal transport have been carried out using the Geant4 application for tomographic emission (GATE) platform. Parameters such as the fiber diameter, numerical aperture, number of fibers and their geometrical arrangement have been studied. Optimal hardware parameters are proposed to obtain homogeneous fluence above the fluence threshold for opsin activation without detrimental thermal effects. Main results. The simulations show that a large fiber diameter and a large numerical aperture are preferable since they allow limiting power concentration and hence the resulting thermal increases at the brain surface. To obtain a volume of 200-500 mm 3 of brain tissues receiving a fluence above the opsin activation threshold for optogenetics or below a phototocixity threshold for photobiomodulation, a 4 fibers configuration is proposed. The optimal distance between the fibers was found to be 4 mm. A practical implementation of the optode has been performed and the corresponding fluence and thermal maps have been simulated. Significance. The Journal of Neural EngineeringOptical and thermal simulations for the design of optodes for minimally invasive optogenetics stimulation or photomodulation of deep and large cortical areas in non-human primate brainOriginal content from this work may be used under the terms of the Creative Commons Attribution 3.0 licence. Any further distribution of this work must maintain attribution to the author(s) and the title of the work, journal citation and DOI. 6 Both authors contributed equally.1741-2552/18/065004+12$33.00 https://doi.org/10.1088/1741-2552/aadf97 J. Neural Eng. 15 (2018) 065004 (12pp) A Dubois et al 2 present study defines a method to optimize the design of optode and the choice of stimulation parameters for optogenetics and more generally light delivery to deep and large volumes of tissues in NHP brain with a controlled irradiance dosimetry. The general guidelines are the use of silica fibers with a large numerical aperture and a large diameter. The combination of several fibers is required if large volumes need to be stimulated while avoiding thermal effects.

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Section: What Is the Expected Temperature Rise And How May It Affectmentioning

confidence: 99%

Optical and thermal simulations for the design of optodes for minimally invasive optogenetics stimulation or photomodulation of deep and large cortical areas in non-human primate brain

et al. 2018

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“…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%

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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“…In general, the size of the light source, the fiber tip (which determines the focus or spread of light), and light intensity can be varied. With these parameters it is possible to calculate the heat produced by the light stimulation [125], and verify that tissue heating is limited to approximately 1°C-the value below which neural and hemodynamic activity are affected [126,127]. Thus, direct stimulations in the lesion area or peri-infarct area may have a negative effect on recovery.…”

Section: Benefits Of Optogeneticsmentioning

confidence: 99%

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

2016

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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.

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Modeling the Spatiotemporal Dynamics of Light and Heat Propagation for In Vivo Optogenetics

Cited by 337 publications

References 41 publications

Optical and thermal simulations for the design of optodes for minimally invasive optogenetics stimulation or photomodulation of deep and large cortical areas in non-human primate brain

Optical and thermal simulations for the design of optodes for minimally invasive optogenetics stimulation or photomodulation of deep and large cortical areas in non-human primate brain

FEF inactivation with improved optogenetic methods

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

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