Rewiring of the Adult Nervous System after Femtosecond Laser Axotomy

Aravinthan D.T. Samuel, Ph.D.

Harvard University, Cambridge, MA
Website

Grant Program:

David Mahoney Neuroimaging Program

Funded in:

June 2007, for 3 years

Funding Amount:

$200,000

Lay Summary

Using Imaging to Understand Adult-Stage Nervous System Regeneration

Researchers will use a newly developed nonlinear optical imaging technique in the transparent worm C. elegans to better understand how nerve circuits direct their own repair after traumatic injuries to the adult brain or spinal cord.

“Femtosecond laser ablation,” in which a new optical surgical scalpel squeezes light into exceedingly short pulses (a millionth of a billionth of a second), will be used to study the molecular processes that enable an adult nervous system to regenerate in this transparent worm. Specifically, researchers will study whether and how calcium signaling enables a neuron to detect initial damage and triggers its own injury response; molecular programming guides the controlled death of injured cells and the pruning of new nerve axons that mistakenly grow in wrong directions; and whether regeneration of nerve axons that connect to appropriate neighboring cells is a replay of the processes used during embryonic nervous system development.

Significance: The findings may provide fundamental insights into conserved molecular pathways for nerve repair that could be exploited in new ways to stimulate effective nerve regeneration after injury.

Abstract

Rewiring of the Adult Nervous System after Femtosecond Laser Axotomy

We propose to develop the nematode C. elegans—an animal with unequalled genetic accessibility—as a new injury model for studies of adult-stage nervous system regeneration. This development is made possible by the advent of femtosecond laser ablation, a new optical scalpel with nanometer-scale precision and exquisite reproducibility. We are now able to snip individual nerve fibers in the adult nervous system of C. elegans, and monitor subsequent regrowth and repair. By systematically quantifying and comparing regenerative ability across different neuronal types, at different stages of worm development, and in different mutant backgrounds, we aim to uncover the genetic and cellular determinants of adult-stage nervous system regeneration.

We will explore such issues as the basic dichotomy in regenerative ability between the central nervous system and the peripheral nervous system; whether regeneration of the adult nervous system replays the same molecular programs for axon growth and guidance that produced the nervous system at the embryonic stage; and whether novel regulation of pathways for programmed cell death enables the worm to remodel damaged neural circuits. The powerful genetics of C. elegans combined with femtosecond laser ablation should drive rapid progress in understanding adult-stage nervous system regeneration, as well as open new doors to identifying its clinical requirements.

Investigator Biographies

Aravinthan D.T. Samuel, Ph.D.

Professor Aravinthan Samuel is a biophysicist and neuroscientist in the Department of Physics and Center for Brain Science at Harvard University. He received his B.A. and Ph.D. degrees from Harvard University, studying bacterial motility and behavior with Prof. Howard Berg. In his own lab, Prof. Samuel is interested in the basis of behavior in a slightly larger organism, the nematode C. elegans. His laboratory focuses on developing novel techniques for manipulating and monitoring the nervous system of this tiny roundworm in studies of neuronal development and regeneration, as well as neuronal computation and animal behavior.