AXON ONSET REMODELING IN RESPONSE TO NETWORK ACTIVITY IN MOUSE CORTICAL NEURONS

Axon Carrying Dendrites (AcD) are a distinctive feature of certain subtypes of pyramidal neurons and interneurons in which axons originate from dendrites, resulting in unique functional properties. While AcD neurons have been identified across species and brain regions, their development and putative activity-dependent axonal plasticity remain unclear. To test this, we examined the developmental profile of layer V AcD pyramidal neurons in the murine primary somatosensory (S1) cortex using Thy1-GFP-M mice. Sensory input was manipulated in vivo via an established whisker deprivation and stimulation paradigm. In parallel, axon onset dynamics were tracked at a single-cell level in vitro using immunofluorescence, confocal microscopy, and longitudinal live-cell imaging in organotypic slice cultures, allowing repeated tracking of individual neurons over time. We found that sensory manipulation induces significant shifts in the prevalence of AcD neurons in young mice, whereas no such plasticity was observed in adults, in which the overall prevalence of AcD neurons was reduced. Importantly, individual neurons were observed to switch their axon origins between somatic and dendritic compartments within days in vitro, suggesting activity-dependent remodeling. Together these findings reveal that AcD identity is not fixed, but rather an activity-dependent maturation process prominent during early development.