Johns Hopkins School of Medicine

Neural Circuit Formation, Function, and Regeneration

The goal of our research is to understand how neural circuits are formed, how they function, and how they can be regenerated. An emphasis is placed on translating what can be learned in robustly regenerative model systems, such as zebrafish, toward the development of novel therapies for stimulating dormant neuronal regenerative capacities in humans. The zebrafish system affords several significant advantages to these studies, including high-resolution in vivo time-lapse imaging and large-scale genetic and chemical screening.

We combine cell-type specific labeling methods and multi-color intravital confocal microscopy to image how complex neuronal morphologies form and how individual neuronal/glial/immuno cell subtypes interact throughout neurogenesis and during regeneration in living zebrafish. This approach provides unique insights into highly dynamic processes attending the development and repair of the central nervous system (CNS).

Many neurodegenerative diseases are typified by the loss of discrete neuronal cell types. To advance studies of how specific neuronal subtypes can be regenerated, we adapted an inducible cell-specific ablation technique to zebrafish. This approach opens several avenues of investigation: 1) Cell-specific regeneration paradigms and associated degenerative disease models, 2) Neural function studies, linking neuronal cell subtypes to discrete behaviors and/or percepts, 3) Correlations between the extent of neuronal injury with the kinetics and specificity of functional recovery, and 4) Large-scale genetic and chemical screens for systematically dissecting the molecular signaling pathways that regulate the regeneration of individual neuronal cell types.