Action Potential Dynamics in Fine Axons Probed with an Axonally Targeted Optical Voltage Sensor

Area of Science:

• Neuroscience
• Biophysics
• Cellular Biology

Background:

• Axonal conduction properties are crucial for neural circuit function but difficult to study due to axon thinness.
• Conventional electrical recording methods are unsuitable for most axons, limiting exploration of their biophysical properties.

Purpose of the Study:

• To develop and utilize a novel method for optically monitoring voltage changes in axons.
• To investigate the use-dependent properties of action potential propagation in different types of axons within the hippocampus.

Main Methods:

• Genetically encoded hybrid voltage sensor (hVOS) with an axonal targeting motif was developed.
• hVOS was expressed in transgenic mice to optically record voltage changes in dentate granule cell axons (mossy fibers) and hilar mossy cell axons in hippocampal slices.

Main Results:

• Distinct action potential velocities were observed in mossy fiber and mossy cell axons.
• Repetitive firing led to action potential broadening and amplitude attenuation in both axon types.
• Differences in frequency-dependent action potential broadening were noted between the two axon populations.

Conclusions:

• Use-dependent action potential broadening and potential failure occur in fine unmyelinated axons, similar to larger nerve terminals.
• Subtle frequency-dependent differences in action potential propagation may influence pathway-specific neuronal excitation.
• The axonally targeted hVOS probe provides a new tool for detailed biophysical studies of neuronal processes.