Parameter Study of Thermogenetics in TRPV1-Expressed Neurons Stimulated by Near-infrared Laser

Abstract

Neuromodulation technique offers wide range of applications in neuroscience research such as functional brain mapping, determination of causal relationship in neural network, Recently, thermogenetic technique is being studied as one of means to modulate neuronal activity. One of the actuators for thermogentics is transient receptor potential cation channel subfamily V member 1 (TrpV1). It is one of TRP families and it is one of temperaturesensitive ion channels in the brain which provides the feasibility of temperature-dependent neuromodulation. However, only a few studies have been made on in vivo application of TRPV1 in neuroscience, and in vivo temperature parameter study on TRPV1 overexpressed neurons’ activation temperature has not been reported. Also, application of near-infrared laser on thermogenetics has not yet been widely applied despite its relatively deep penetration depth in biological tissue. The aim of the study was to verify the feasibility of TRPV1- mediated thermogenetics as a neuromodulation technique, to determine the effect of thermal stimulation on neuronal excitation by different temperature parameters, and to find the optimal parameters for thermogenetic stimulation. AAV5-hSyn-TRPV1-mCherry was injected in rat’s motor cortex, then different intensities of NIR laser was used to induce thermal stimulation on cortex. The electrophysiological recording showed over-expressing TRPV1 improved sensitivity to thermal stimulation, lowering required temperature for channel activation as low as 2C. Probability of neuronal excitation has also increased, and increased burst firing activity and shorter ISI was observed when exposed to NIR induced thermal radiation compared to control group. The result data shows 50mW of NIR laser intensity appears to be enough to draw out neuronal activation without possible tissue damage.