Unveiling the cell biology of hippocampal neurons with dendritic axon origin

Abstract

In mammalian axon-carrying-dendrite (AcD) neurons, the axon emanates from a basal dendrite, instead of the soma, to create a privileged route for action potential generation at the axon initial segment (AIS). However, it is unclear how such unusual morphology is established and whether the structure and function of the AIS in AcD neurons is preserved. Here, we show that the AcD neurons follow an intrinsically encoded developmental program where a single precursor neurite first gives rise to the axon and then to the AcD. The AIS possesses a similar cytoskeletal architecture as the canonical AIS that stems from the soma, and similarly functions as a trafficking barrier to retain axon-specific molecular composition. However, unlike soma-derived AIS, the AIS of AcD neurons does not undergo homeostatic-plasticity, contains less cisternal organelles and receives fewer inhibitory inputs. These distinct features of the AIS could account for the higher intrinsic excitability of AcD neurons. HighlightsO_LIThe development of AcD neurons is intrinsically driven and does not depend on specific connectivity patterns C_LIO_LIAcD neurons generate the axon and AcD from the same precursor neurite C_LIO_LIThe stem dendrite of an AcD neuron displays axon-like microtubule organization C_LIO_LISimilar to the AIS emerging from the soma, the AIS of AcD neurons can selectively filter dendritic cargo C_LIO_LIThe AIS of AcD neurons does not undergo chronic homeostatic plasticity and receives fewer inhibitory inputs C_LI