In Vitro Reconstruction of Axonal Heat Sensing with a Photothermal Nerve-on-a-Chip

Area of Science:

• Neuroscience
• Biotechnology
• Materials Science

Background:

• Axons are primary sites for detecting and transducing thermal signals.
• The localized thermal response of axons is not well understood.
• Existing methods lack the resolution to study axonal thermosensation at the required scale.

Purpose of the Study:

• To develop a platform for in vitro reconstruction of axonal thermosensation.
• To investigate localized, millisecond-scale thermal stimulation of axons.
• To analyze heat-evoked neural activity and temperature coding in sensory neurons.

Main Methods:

• Integration of graphene photothermal heaters with microelectrode arrays in microchannels.
• Development of a nerve-on-a-chip platform for axon guidance.
• Localized, millisecond-scale thermal stimulation and simultaneous extracellular recording of action potentials.

Main Results:

• Demonstrated rapid and reproducible heat-evoked responses in rat dorsal root ganglion neurons.
• Observed thermoreceptor-mediated rapid desensitization in response to heat stimuli.
• Identified distinct thermal-response profiles in human iPSC-derived sensory neurons, showing delayed heat responsiveness.

Conclusions:

• The photothermal nerve-on-a-chip platform enables high-resolution analysis of axonal temperature coding.
• The platform is a scalable tool for studying peripheral thermosensation in various conditions.
• Findings provide new insights into the mechanisms of heat detection and response in different neuronal types.