Measurement, modeling, and prediction of temperature rise due to optogenetic brain stimulation

Arias-Gil, Gonzalo; Ohl, Frank W.; Takagaki, Kentaroh; Lippert, M.

doi:10.1117/1.nph.3.4.045007

Cited by 57 publications

(61 citation statements)

References 19 publications

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“…Previous approaches such as Monte Carlo simulations with finite-difference time-domain (FDTD) methods (Stujenske et al, 2015) or empirical fitting of experimental results (Arias-Gil et al, 2016;Podgorski and Ranganathan, 2016) did not reach micrometer and millisecond resolution. Indeed, to simulate the propagation of tightly focused beams would require introducing diffraction in the Monte Carlo code, which is intrinsically difficult (Brandes et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

“…Temperature rise under the typical illumination conditions for 1P optogenetics (i.e., wide-field illumination through optical fibers and long, 0.5-60 s exposure time) has been investigated both theoretically, using Monte Carlo with finite-difference time-domain schemes (Stujenske et al, 2015) or the finiteelement method (Shin et al, 2016), and experimentally using thermocouples (Shin et al, 2016;Stujenske et al, 2015), quantum dots (Podgorski and Ranganathan, 2016), or infrared (IR) cameras (Arias-Gil et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

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Temperature Rise under Two-Photon Optogenetic Brain Stimulation

et al. 2018

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In recent decades, optogenetics has been transforming neuroscience research, enabling neuroscientists to drive and read neural circuits. The recent development in illumination approaches combined with two-photon (2P) excitation, either sequential or parallel, has opened the route for brain circuit manipulation with single-cell resolution and millisecond temporal precision. Yet, the high excitation power required for multi-target photostimulation, especially under 2P illumination, raises questions about the induced local heating inside samples. Here, we present and experimentally validate a theoretical model that makes it possible to simulate 3D light propagation and heat diffusion in optically scattering samples at high spatial and temporal resolution under the illumination configurations most commonly used to perform 2P optogenetics: single- and multi-spot holographic illumination and spiral laser scanning. By investigating the effects of photostimulation repetition rate, spot spacing, and illumination dependence of heat diffusion, we found conditions that make it possible to design a multi-target 2P optogenetics experiment with minimal sample heating.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Temperature Rise under Two-Photon Optogenetic Brain Stimulation

et al. 2018

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“…The unfavorable stoichiometry of one 50 transported ion for each absorbed photon necessitates continuous illumination at high light power. The 51 resulting tissue heating 9,10 and phototoxicity 11 restrict the optically addressable brain volume that can 52 be efficiently silenced. Furthermore, ion-pumping microbial rhodopsins exhibit a decline in photocurrent 53…”

Section: Optogenetic Tools 40mentioning

confidence: 99%

High-efficiency optogenetic silencing with soma-targeted anion-conducting channelrhodopsins

Mahn

Gibor

Malina

et al. 2017

Preprint

102

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24Optogenetic silencing allows time-resolved functional interrogation of defined neuronal populations. 25However, the limitations of inhibitory optogenetic tools impose stringent constraints on experimental 26 paradigms. The high light power requirement of light-driven ion pumps and their effects on intracellular 27 ion homeostasis pose unique challenges, particularly in experiments that demand inhibition of a 28 widespread neuronal population in vivo. Guillardia theta anion-conducting channelrhodopsins (GtACRs) 29 are promising in this regard, due to their high single-channel conductance and favorable photon-ion 30 stoichiometry. However, GtACRs show poor membrane targeting in mammalian cells, and the activity of 31 such channels can cause transient excitation in the axon due to an excitatory chloride reversal potential 32 in this compartment. Here we address both problems by enhancing membrane targeting and subcellular 33 compartmentalization of GtACRs. The resulting GtACR-based optogenetic tools show improved 34 photocurrents, greatly reduced axonal excitation, high light sensitivity and rapid kinetics, allowing highly 35 efficient inhibition of neuronal activity in the mammalian brain. 36 37 amplitudes of up to 90% within a minute of illumination, leading to reduced silencing efficacy over time 54 12,8,13 . Because of their insensitivity to electrochemical gradients, ion-pumping microbial rhodopsins can 55 shift the concentrations of intracellular ions to non-physiological levels. In the case of halorhodopsin, 56 this can lead to accumulation of chloride in the neuron, inducing changes in the reversal potential of 57 GABAergic synapses 14 . While in the case of archaerhodopsin this can increase the intracellular pH, 58 inducing action potential-independent Ca 2+ influx and elevated spontaneous vesicle release 13 . 59Furthermore, the hyperpolarization mediated by ion-pumping activity together with the fast off kinetics 60 can lead to an increased firing rate upon termination of the illumination 6,13 . 61Anion-conducting channelrhodopsins (ACRs), a newly established set of optogenetic tools 15,16,17 , are 62 distinct from ion-pumping rhodopsins in two major aspects: first, they can conduct multiple ions during 63 each photoreaction cycle. This increased photocurrent yield per photon makes channelrhodopsins 64 superior in terms of their operational light-sensitivity. Second, conducting ions according to the reversal 65 potential, ACRs are more likely to avoid non-physiological changes in ion concentration gradients. A 66 light-gated chloride conductance will shunt membrane depolarization, which can be used to effectively 67 clamp the neuronal membrane potential to the reversal potential of chloride, given that the ion 68 permeability is sufficiently high. Anion-conducting channelrhodopsins could therefore relieve constrains 69 imposed by ion-pumping rhodopsins. The naturally-occurring anion-conducting channelrhodopsins 70 (nACRs) from the cryptophyte alga Guillardia theta 16 are particularly interesting in this ...

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“…10 In the analysis of the color photographs and the numbered sections, the head model was segmented into eight types of tissue, including scalp, skull, CSF, muscle, visible artery, vein blood vessels, gray and white matter. We chose every four continuous pixels in both anterior-posterior and left-right directions in two continuous slices to form voxels of 0:04 Â 0:04 Â 0:04 cm 3 . This was the voxel size used to balance the computation parts in the simulation and get it more precise and real.…”

Section: Methods and Materials 21 Vch Brain Modelmentioning

confidence: 99%

“…1,2 While the temperature variation or heat generation e®ect has been well studied in the research of light therapy, the quantitative knowledge of light propagation and penetration depth is rare. 3 There is no doubt that for those light stimulation and treatment¯elds, the penetration depth of light is critical for both research and clinical application, especially on the issue for precision of personal medicine, quantitative-guide treatment, optimization of the light therapy parameters, and safety control. There is sparse experiment study on light penetration depth for human structured tissues, only semi-in¯nite phantom or layered phantom study were published.…”

Section: Introductionmentioning

confidence: 99%

Photon penetration depth in human brain for light stimulation and treatment: A realistic Monte Carlo simulation study

Xue²,

Wang³

et al. 2017

J. Innov. Opt. Health Sci.

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Light has been clinically utilized as a stimulation in medical treatment, such as Low-level laser therapy and photodynamic therapy, which has been more and more widely accepted in public. The penetration depth of the treatment light is important for precision treatment and safety control. The issue of light penetration has been highlighted in biomedical optics¯eld for decades. However, quantitative research is sparse and even there are con°icts of view on the capability of near-infrared light penetration into brain tissue. This study attempts to quantitatively revisit this issue by innovative high-realistic 3D Monte Carlo modeling of stimulated light penetration within high-precision Visible Chinese human head. The properties of light, such as its wavelength, illumination pro¯le and size are concern in this study. We made straightforward and quantitative comparisons among the e®ects by the light properties (i.e., wavelengths: 660, 810 and 980 nm; beam types: Gaussian and°at beam; beam diameters: 0, 2, 4 and 6 cm) which are in the range of light treatment. The¯ndings include about 3% of light dosage within brain tissue; the combination of Gaussian beam and 810 nm light make the maximum light penetration §

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Measurement, modeling, and prediction of temperature rise due to optogenetic brain stimulation

Cited by 57 publications

References 19 publications

Temperature Rise under Two-Photon Optogenetic Brain Stimulation

Temperature Rise under Two-Photon Optogenetic Brain Stimulation

High-efficiency optogenetic silencing with soma-targeted anion-conducting channelrhodopsins

Photon penetration depth in human brain for light stimulation and treatment: A realistic Monte Carlo simulation study

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