Human TRPV1 is an efficient thermogenetic actuator for chronic neuromodulation

Area of Science:

• Neuroscience
• Biotechnology
• Medical Engineering

Background:

• Thermogenetics offers a novel approach to neuromodulation by utilizing heat-sensitive ion channels.
• Clinical translation requires studying human ion channels, safe temperature thresholds for in vivo brain activation, and chronic application safety.

Purpose of the Study:

• To establish a framework for in vivo thermogenetic neuromodulation using the human TRPV1 channel (hTRPV1).
• To assess the safety and efficacy of chronic neuromodulation with hTRPV1 in mouse brains.

Main Methods:

• Targeted expression of hTRPV1 in excitatory neurons of the mouse brain.
• Activation of hTRPV1 using a fiber-coupled infrared laser within a non-harmful temperature range.
• Evaluation of neuronal firing, locomotion, and brain tissue for injury after repeated stimulation.

Main Results:

• Successful induction of neuronal firing and stimulation of locomotion in mice via hTRPV1 activation.
• Demonstration of repeated neuromodulation without observable brain tissue damage.
• Validation of a non-harmful temperature range for in vivo thermogenetic activation.

Conclusions:

• Thermogenetics using hTRPV1 is a viable and safe neuromodulation strategy in vivo.
• This approach provides a foundation for advancing brain research and developing therapies for neuropathologies.
• The study addresses key challenges for the clinical application of thermogenetics.