Investigation of Serotonergic Signaling Mechanisms that Promote Regeneration Following Spinal Cord Injury

Spinal cord injury often leads to loss of function below the injury, greatly reducing patient life expectancy and quality and, because the human nervous system lacks the ability to effectively self-repair, even partial recovery of function below the injury is rare. Mammals possess endogenous neuronal progenitor cells with stem cell-like properties that, under the right conditions, can be induced to proliferate and differentiate into new neurons. Yet, mammals have a very low capacity for neuronal regeneration when compared to fish and amphibians, which are capable of rapid regeneration of a wide variety of tissues and structures. This proposal will exploit the superior regenerative capacity and unique experimental toolbox available in the larval zebrafish to examine the roles of serotonergic signaling in promoting regeneration and functional recovery from spinal cord injuries. The aims described in this proposal will be used as a basis for future work on the pathways and mechanisms that underlie recovery of function following spinal cord injury.

Research Focus: Spinal Cord Injury

Year 1 Progress Report:

This project explores the effects of serotonergic signaling on different aspects of spinal cord regeneration. During the first year, we accomplished many of the essential objectives of the project. We improved our spinal cord injury protocol and characterized the timecourse of regeneration and functional recovery from injury. We also developed and characterized approaches for activating and ablating the neurons that provide serotonin to the spinal cord. This will enable control of serotonergic signaling to test its influences on spinal cord regeneration.