High-resolution mapping of injury-site dependent functional recovery in a single axon in zebraﬁsh

COMMUNICATIONS BIOLOGY, 2020 · DOI: https://doi.org/10.1038/s42003-020-1034-x · Published: June 12, 2020

Regenerative Medicine Neurology Research Methodology & Design

Simple Explanation

In this paper the authors demonstrate that, using two-photon microscopy, the M-axon does not regenerate poorly per se, but that it rather can regrow very rapidly with crucial aspects of its function also completely restored in days. The discrepancy to earlier ﬁndings is explained from the fact that, similarly as in the rodent optic nerve, regenerative capacity of the M-axon is not distributed homogeneously and is worse both after injury very close to the soma and very far from it. Hence the M-cell of zebraﬁsh is a powerful model to study the nature of positional effects in axon regeneration and—because of its unique association with short-latency escapes—to monitor functional recovery after targeted injury of one single axon at a temporal resolution of less than one day.

Study Duration

10 days

Participants

Zebrafish larvae (5 dpf)

Evidence Level

Not specified

Key Findings

1
Mauthner (M-) axon might regenerate better when the spinal cord is injured closer to the soma of the M-cell.
2
Targeted proximal injury reveals rapid axonal regeneration in the Mauthner cell.
3
High-resolution mapping of regenerative capacity across the length of the Mauthner axon.

Research Summary

This approach revealed that the M-axon can regenerate very rapidly and that essential functions of the behavior driven by this neuron are fully recovered in just days. As we report here, the regenerative capacity is not distributed uniformly across the axon and its decline after distant injury explains earlier reports of poor regeneration of the M-axon. Additionally, it shows one of the major factors seen currently as a potent leverage to understand mechanisms that enable or inhibit regeneration: at least in zebraﬁsh larvae it exhibits an injury-site dependent switch that decides between rapid and functional regeneration or poor regeneration.

Practical Implications

Understanding Regeneration

The study provides insights into the mechanisms that govern axon regeneration in vertebrates, particularly the role of the injury site's proximity to the soma.

Therapeutic Potential

The findings may contribute to the development of strategies for promoting axon regeneration and functional recovery after spinal cord injury in mammals.

Drug discovery

It involves both rapid and slow processes, which makes it interesting to explore what could be the switch that decides between the two. And its distant-dependent regeneration makes it a good model in which to study how distance-dependent processes interfere with regeneration, an approach that is currently seen as very promising

Study Limitations

1
The study was conducted on zebrafish larvae, and the findings may not be directly applicable to mammals due to differences in the regenerative capacity of the nervous system.
2
The study focused on a single type of neuron, the Mauthner axon, and the regenerative capacity of other types of neurons in the spinal cord may differ.
3
The study only examined the recovery of specific motor functions, such as escape latency, and other aspects of neurological function may not have been fully restored.

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