# Increased synaptic turnover in injured cortical axons: exploring the role of SARM1 ablation

## TL;DR

This study investigates how SARM1 affects synaptic changes in the cortex after injury, finding that SARM1 is not involved in synaptic remodeling after axonal damage.

## Contribution

The study reveals that SARM1 does not contribute to synaptic plasticity in the proximal axon following acute injury in the adult cortex.

## Key findings

- SARM1 is not necessary for maintaining baseline cortical synaptic connectivity.
- After axotomy, the proximal axon showed increased synapse loss, but SARM1 ablation did not affect this process.
- Synaptic turnover and density were similar between wild-type and SARM1KO groups under normal conditions.

## Abstract

Programmed axon degeneration significantly affects neural connectivity, however, the underlying mechanisms remain poorly understood, particularly in cortical regions. Sterile Alpha and TIR motif-containing protein 1 (SARM1) is a known regulator of axon degeneration in the peripheral nervous system, but its role in cortical axon plasticity, particularly during injury conditions, remains unclear. This study examined the role of SARM1 in synaptic connectivity and remodelling in the adult sensory-motor cortex under normal physiological conditions and following acute axonal injury.

Adult male Thy1-GFP-M mice (3–12 months) expressing EGFP in excitatory neurons were also either wild-type (WT-GFP) or null for SARM1 (SARM1KO-GFP). Using in vivo multiphoton microscopy, long cortical axon segments (~335 μm ± 140 μm), with terminaux and en passant synaptic boutons in the upper layers of the cortical neuropil, were repeatedly imaged at 48-h intervals to assess axon morphology, synaptic density, and synaptic turnover in the presence and absence of SARM1.

Without injury, axon morphology, synaptic density, and turnover were similar between WT and SARM1KO groups, suggesting that SARM1 is not necessary for maintaining baseline cortical synaptic connectivity. Following axotomy by laser lesion, the non-degenerating proximal axon (still connected to the soma) showed significant changes in synaptic plasticity, with an increased rate of loss of synapses.

Our findings suggest that SARM1 plays no role in the remodelling of synapses in the proximal axon after an acute axonal injury.