Novel method to assess axonal excitability using channelrhodopsin-based photoactivation

Area of Science:

• Neuroscience
• Cellular Physiology
• Biophysics

Background:

• Direct measurement of axonal excitability is challenging due to difficulties in obtaining intracellular recordings.
• Understanding axonal excitability is crucial for deciphering neuronal signal processing, especially in primary afferent neurons (PANs).
• Current methods are insufficient for studying the excitability of distal neuronal endings in situ.

Purpose of the Study:

• To introduce and validate an innovative methodology for measuring local axonal excitability in channelrhodopsin (ChR2)-expressing neurons.
• To investigate differences in excitability along PAN axons and their impact on somatosensory encoding.
• To assess the effect of inflammation on the neuronal transformation process.

Main Methods:

• Developed a technique involving spatially and temporally precise photoactivation of ChR2 in neurons.
• Recorded resulting spike trains from remote sites to infer local excitability.
• Validated the method in primary afferent neurons (PANs) and examined the effects of inflammation.

Main Results:

• Demonstrated that axonal excitability varies between distal endings and proximal segments of PAN axons.
• Showed that the stimulus-to-spike transformation process differs among individual PANs.
• Confirmed that inflammation significantly affects the stimulus-to-spike transformation process in PANs.

Conclusions:

• The novel ChR2-based photoactivation method allows for localized measurement of axonal excitability.
• This technique provides new insights into the heterogeneity of PAN excitability and encoding processes.
• The study highlights the utility of this method for understanding early somatosensory encoding and the impact of inflammatory conditions.