In this project we have analyzed neurogenesis in the axolotl salamander brain during homeostasis and regeneration and developed methodology to analyse neuronal projections and connections. Neurogenesis, the generation of new neurons from stem or progenitor cells, occurs universally during embryonic development across all animals. Following embryonic development, certain species maintain ongoing neurogenesis into adulthood to varying degrees. In humans, regions like the hippocampus exhibit continuous adult neurogenesis, producing approximately 700 new neurons daily. Conversely, species like teleost fish and amphibians experience lifelong growth, necessitating constant cell generation in multiple brain areas. In zebrafish and axolotl, continual neurogenesis is observed in various brain regions, including the telencephalon, mesencephalon, and olfactory bulb. Notably, these species possess the unique ability to regenerate lost neurons after injury, a feature distinct from mammals, where neuronal death typically results in glial cell hypertrophy and scar formation, impeding neuronal regeneration. Both adult neurogenesis and neural regeneration face a crucial challenge: integrating newborn cells into existing neural networks. Maintaining and restoring neural connectivity and circuit function is vital for controlling animal behavior and regulating physiology. Thus, newborn cells must be appropriately integrated and connected to target cells to ensure the functionality of the neural network is preserved or restored. The objectives of this Marie Skłodowska Curie Action (MSCA) have been to (a) Develop in vivo imaging of neurogenesis during homeostasis and regeneration of the axolotl brain, to (b) set up in vivo imaging of functional neural circuits, their growth and regeneration in the axolotl and (c) develop methods to visualize functional connections of neurons. We have been successful in developing a variety of methods visualize functional connections of neurons which will in the future be useful to determine neuronal circuit recovery after brain regeneration in the axolotl.
