Thermal constraints on in vivo optogenetic manipulations

• Published in: Nature neuroscience Vol. 22; no. 7; pp. 1061 - 1065
• Main Authors: Owen, Scott F., Liu, Max H., Kreitzer, Anatol C.
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.07.2019; Nature Publishing Group
• Subjects: 13; 14; 59; 631/1647/2253; 631/378/3920; 64; 9/74; Action Potentials - drug effects; Action Potentials - radiation effects; Animal Genetics and Genomics; Animals; Barium Compounds - pharmacology; Behavioral Sciences; Biological Techniques; Biomedical and Life Sciences; Biomedicine; Brain; Brief Communication; Cerebral Cortex - cytology; Cerebral Cortex - physiology; Chlorides - pharmacology; Corpus Striatum - cytology; Corpus Striatum - physiology; Experiments; Genetics; Hippocampus - cytology; Hippocampus - physiology; Hot Temperature; Illumination; Information processing; Ion Transport - drug effects; Ion Transport - radiation effects; Light; Mice; Motor Activity - radiation effects; Neostriatum; Neural stimulation; Neurobiology; Neurons; Neurons - drug effects; Neurons - physiology; Neurons - radiation effects; Neurophysiology; Neurosciences; Optical properties; Optics; Optogenetics - methods; Patch-Clamp Techniques; Physiological aspects; Physiology; Potassium; Potassium - metabolism; Potassium Channels, Inwardly Rectifying - drug effects; Potassium Channels, Inwardly Rectifying - metabolism; Potassium Channels, Inwardly Rectifying - radiation effects; Potassium conductance; Research Design; Resistance; Rotational behavior; Temperature; Thermal properties; United States
• ISSN: 1097-6256; 1546-1726
• DOI: 10.1038/s41593-019-0422-3

A key assumption of optogenetics is that light only affects opsin-expressing neurons. However, illumination invariably heats tissue, and many physiological processes are temperature-sensitive. Commonly used illumination protocols increased the temperature by 0.2–2 °C and suppressed spiking in multiple brain regions. In the striatum, light delivery activated an inwardly rectifying potassium conductance and biased rotational behavior. Thus, careful consideration of light-delivery parameters is required, as even modest intracranial heating can confound interpretation of optogenetic experiments. Optogenetics has revolutionized neuroscience, but intracranial illumination can cause off-target effects. Owen et al. identify a temperature-sensitive potassium current that modulates neuronal activity and behavior independent of opsin expression.