Modeling the effect of temperature on membrane response of light stimulation in optogenetically-targeted neurons

Abstract

Optogenetics is revolutionizing neuroscience but an often neglected effect of light stimulation of the brain is the generation of heat. In extreme cases, light-generated heat kills neurons but mild temperature changes alter neuronal function. In this work, we investigated heat transfer in brain tissue for common optogenetic protocols using the finite element method. We then modeled channelrhodopsin-2 in a single-and a spontaneousfiring neuron to explore the effect of heat in light stimulated neurons. We found that, at commonly used intensities, laser radiation considerably increases the temperature in the surrounding tissue. This effect alters action potential size and shape and cause increase in spontaneous firing frequency in a neuron model. However, the shortening of activation time constants generated by heat in the single firing neuron model produce AP failures in response to light stimulation. We also found changes in the power spectrum density and a reduction in the time required for synchronization in an interneuron network model of gamma oscillations. Our findings indicate that light stimulation with intensities used in optogenetic experiments may affect neuronal function not only by direct excitation of light sensitive ion channels and/or pumps but also by generating heat. This approach serves as a guide to design optogenetic experiments that minimize the role of tissue heating in the experimental outcome.PeerJ Preprints | https://doi.org/10.7287/peerj.preprints.27248v1 | CC BY 4.0 Open Access | rec:

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“…Further chronic studies of thermal and photonic impact using this platform may inform device engineering for translational work toward chronic stability in the freely behaving subject. During in vivo experiments, it is also expected that thermal load on the heart further decreases due to perfusion ( 46 ) (see Materials and Methods for more information).…”

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“…Here, a shortterm temperature increase of 2.55 °C occurs at the skull/LED interface with an average increase of 0.247 °C after 5 s. Temperatures at the brain/CSF interface show no pulsatile component. Because of the low increases in temperature in the worst-case scenario that does not include perfusion cooling, we do not expect substantial thermally driven changes in neuronal activity (38).…”

The activated synaptic terminals beyond the light illumination range affect the results of optogenetics

“…Light-induced changes in temperature may affect neuronal activity and behavior [9]. Temperature can increase by about 2.6°C in 1 min for blue light stimulation (20 mW of power), and a 2°C raise in temperature increased the firing frequency of neurons in a network model of gamma oscillations [11]. In our study, brief LED light pulse (3 ms) with a maximum 2.3 mw power were applied individually (0.033 Hz), which is a relatively common parameter in optogenetic experiments [25].…”

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