19-P044 Neuronal circuit in the spinal cord of zebrafish before and after lesion

In contrast to humans, zebrafish regain locomotor ability within 6 weeks after a spinal cord lesion. We aim to study the main components of the locomotor circuit in unlesioned adult zebrafish and changes thereof after lesion and during recovery. To this aim we use transgenic and immunohistochemical markers specific for different cell types. Recently, we have shown that lost motor neurones are replaced by newly born motor neurones that mature and are integrated into the spinal circuitry after a spinal lesion [Reimer et al., 2008. J. Neurosci. 28, 8510–8516]. Here, we show by BrdU labelling that serotoninergic cells are also newly born after lesion. Combining immunohistochemistry for serotonin and choline acetyl transferase revealed that serotoninergic cells are distinct from motor neurones. Overall numbers of serotoninergic cells were increased 4.5-fold at 2 weeks post-lesion compared to unlesioned fish and remained at this increased level for up to at least 6 weeks post-lesion, when functional recovery plateaus. In contrast, parvalbuminergic cells do not change in number 2 weeks after a spinal lesion and are not labelled by BrdU. This demonstrates cell type specific differences in cell death and proliferation in the lesioned spinal cord. We are also analysing changes in other cell types, such as inhibitory interneurones, and in the density of serotoninergic and dopaminergic fibers in the lesioned spinal cord. We hope that these studies will increase our understanding of the adaptive changes in the spinal circuitry that allow adult zebrafish to successfully recover form a lesion. This work is funded by Robert Packard Center for ALS Research at Johns Hopkins and Euan MacDonald Centre for Motor Neurone Disease.