Activity-dependent co-ordination of axonal and dendritic maturation

Neurons are polarised cells whose function critically depends on distinct sub-cellular compartments: axons and dendrites. In axons, a specialised region – the axon initial segment (AIS) – regulates neuronal excitability and polarity and is a focal site for developmental plasticity. Maturing dendrites also undergo significant plastic modifications that can include the pruning of entire branches. These processes of activity-dependent AIS and dendritic development are individually well understood, but their potential to influence each other remains critically understudied. Does dendritic pruning shape the developing AIS? And does AIS plasticity affect dendritic maturation? These are important questions because axo-dendritic interactions in mature neurons – and therefore the functional operation of neuronal circuits – depend on cells co-ordinating the development of the two compartments. Here, I will take advantage of a cell type that undergoes activity-dependent dendritic pruning at the time that its AIS experiences significant maturational changes, to ask how neurons co-ordinate these processes. By linking morphological, transcriptomic, and functional features of AIS maturation to dendritic pruning in the same cells, and by selectively manipulating either dendritic maturation or AIS development, I will uncover how each sub-cellular compartment influences each other’s development to build functional cells that contribute to healthy brain function.