Imaging functional integration of newborn neurons into neural circuits of the axolotl brain
Post embryonic growth and regeneration require new cells to integrate into the network of existing cells. In the case of the brain it is extremely important to maintain and restore circuit function, such that behaviors can be executed correctly. To study such processes a system that fulfills both post-embryonic growth as well as regeneration is needed. Furthermore, since neural circuit functions are highly dynamic the need for in vivo approaches is evident. In mammalian systems where neurogenesis occurs throughout life in restricted brain regions such approaches are technically challenging.
Here, I propose to use the axolotl (Ambystoma mexicanum) brain to understand the dynamic remodeling of neural circuits through the addition of newborn neurons during post-embryonic growth and regeneration. I will establish a high resolution intra-vital in vivo imaging approach to address the dynamics of neurogenesis and remodeling of neural circuits in the telencephalon and the optic tectum. Using this setup in combination with genetically encoded calcium indicators I will generate activity maps of these regions in the presence or absence of defined stimuli and address their functional remodeling during growth and their restoration after injury. Furthermore, I will develop and adapt methods to visualize the functional connections of neurons in axolotl. Together, this work will provide fundamental insights into the functional maintenance and regeneration of neural circuits and the dynamics of how new neurons integrate in vivo which has not yet been achieved in any vertebrate system.