Characterization of fiber-optic light delivery and light-induced temperature changes in a rodent brain for precise optogenetic neuromodulation

Abstract

Understanding light intensity and temperature increase is of considerable importance in designing or performing optogenetic experiments. Our study describes the optimal light power at target depth in the rodent brain that would maximize activation of light-gated ion channels while minimizing temperature increase. Monte Carlo (MC) simulations of light delivery were used to provide a guideline for suitable light power at a target depth. In addition, MC simulations with the Pennes bio-heat model using data obtained from measurements with a temperature-measuring cannula having 12.3 mV/°C of thermoelectric sensitivity enabled us to predict tissue heating of 0.116 °C/mW on average at target depth of 563 μm and specifically, a maximum mean plateau temperature increase of 0.25 °C/mW at 100 μm depth for 473 nm light. Our study will help to improve the design and performance of optogenetic experiments while avoiding potential over- and under-illumination.

Micro-Reflector Integrated Multichannel μLED Optogenetic Neurostimulator With Enhanced Intensity

“…When compared with optical fiber based stimulators, our proposed array is advantageous in terms of multi-site stimulation and motivates toward an untethered wireless device. In addition, our array demonstrated improved heat dissipation (<1 • C), compared to an optical fiber based stimulator reported by Y. Shin et al where a temperature increase of 1-1.5 • C was observed (Shin et al, 2016). Finally, the effectiveness of the reflectorcoupled LEDs for localized light induction of optogenetic DNA was validated in vitro using human embryonic kidney cells.…”

The firing rate speed code of entorhinal speed cells differs across behaviorally relevant time scales and does not depend on medial septum inputs

“…Our data using transient and temporally precise optogenetic silencing of medial septum subpopulations demonstrate that speed tuning of firing rates in the entorhinal cortex does not depend on medial septum inputs. One caveat of optogenetic studies is that the delivery of laser light into brain tissue results in local heating (Arias- Gil et al, 2016;Shin et al, 2016), which most likely results in a local increase of neuronal firing rates. Nevertheless, our data using optogenetic silencing of cholinergic neurons are consistent with previous experimental data from experiments using less temporally precise pharmacogenetic modulation of medial septum cholinergic neurons (Carpenter et al, 2017).…”

“…In the following, we refer to this group as the laser control group. In addition to visual effects, delivery of laser light into brain tissue results in local heating of brain tissue (Arias- Gil et al, 2016;Shin et al, 2016), which can affect brain activity, most likely resulting in a local increase of neuronal firing rates. To control for heating and other possible unwanted effects of laser light delivery into the brain, we performed control experiments in ChAT-Cre mice conditionally expressing green fluorescent protein (GFP) in cholinergic MSDB neurons, mimicking the sparse expression of virally transduced protein observed in the experimental groups for optogenetic silencing of MSDB subpopulations.…”

Temperature Rise under Two-Photon Optogenetic Brain Stimulation

“…So far, experimental methods to evaluate light induced heating during optogenetics experiments have used thermocouples, with millimeter-long tips and diameters ranging between 220 and 500 mm, which translates into a millimeter-range sensitive region (Podgorski and Ranganathan, 2016;Shin et al, 2016;Stujenske et al, 2015), or a thermal camera allowing a spatial resolution of $50 mm (Arias-Gil et al, 2016). These probes were well adapted to measure temperature rises averaged on large area but lack the necessary precision to predict the spatial heat distribution induced by 2P patterned light at micrometer scale.…”

“…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).…”