Axonal structure-function relationships across experimental modalities

Area of Science:

• Neuroscience
• Biophysics
• Neuroimaging

Background:

• The structure-function relationship of myelinated nerve fibers links physical properties to signal transmission speed.
• Investigating this relationship is crucial for understanding neural communication.

Purpose of the Study:

• To investigate the structure-function relationship in the rat transcallosal motor pathway.
• To compare functional (conduction velocity) and structural (axon diameter, g-ratio) metrics.

Main Methods:

• Combined optogenetics, local field potentials (LFPs), and diffusion MRI (dMRI) for functional and structural analysis.
• Quantified axon diameter and g-ratio using dMRI and transmission electron microscopy (TEM).
• Assessed and corrected for tissue shrinkage during TEM preparation.

Main Results:

• TEM revealed diameter-dependent axonal shrinkage (37%), impacting structural estimates.
• dMRI-based diameter estimates were biased toward larger axons.
• Functional conduction times correlated with smaller axons, while dMRI predicted faster conduction than observed.

Conclusions:

• Structural and functional metrics exhibit different sensitivity profiles.
• Accounting for modality-dependent sensitivities is essential for accurate structure-function analysis.
• This work advances understanding of microstructure's role in neural communication.