Cellular neuroscience group dives deep into activation-induced structural changes in neurons

The neuron is a polarized cell that first integrates synaptic inputs over the cell body and dendrites. Strategically located between the somatodendritic and axonal compartments, the axon initial segment (AIS) collects inputs together and “decides” which signals are taken forward.

The AIS generates the action potentials, and separates the axon from the cell body to maintain its molecular identity. The length and location of AIS regulates how strong input will be taken forward. Generated axon potentials travel along axons to be received by other neurons.

Key organizer protein in AIS is ankyrin G, which is linked to actin cytoskeleton via betaIV-spectrin. Actin structures have been implicated in various AIS functions, including structural maintenance of the AIS.

The AIS is capable of large-scale reorganization and relocation in a neuron activity-dependent manner. This provides neurons a way to regulate and balance their output to everchanging inputs.

We hypothesized that the AIS actin cytoskeleton dynamically re-organizes upon neuronal activation and this re-organization allows re-ordering of the other AIS proteins.

The AIS actin cytoskeleton is dim and no clear actin structures can be identified by using traditional techniques of light microscopy. Therefore, we imaged the fine structures of the actin cytoskeleton using the structured illumination microscopy (SIM) super-resolution technique.

Our results indicate that active re-organization of the actin cytoskeleton is required for proper AIS plasticity. We suggest a 3-step working model: 1) destabilization of actin rings allowing higher mobility of AIS proteins, 2) translocation of transmembrane and other AIS proteins, and then 3) re-stabilization of the structure (Figure).

This study, led by PhD student David Micinski, is now online in Frontiers in Molecular Neuroscience: https://frontiersin.org/articles/10.3389/fnmol.2024.1376997/full