title: Activity-dependent and activity-independent development of the axon initial segment.
abstract: The axon initial segment (AIS) is the site of spike initiation in neurons. Previous studies revealed that spatial distribution of the AIS varies greatly among neurons to meet their specific needs. However, when and how this differentiation arises is unknown. Neurons in the avian nucleus laminaris (NL) are binaural coincidence detectors for sound localization and show differentiation in the distribution of the AIS, with shorter length and a more distal position from the soma with an increase in tuning frequency. We studied these characteristics of the AIS in NL neurons of the chicken during development and found that the AIS differentiates in its distribution after initial formation, and this is driven by activity-dependent and activity-independent mechanisms that differentially regulate distal and proximal boundaries of the AIS. Before hearing onset, the ankyrinG-positive AIS existed at a wide stretch of proximal axon regardless of tuning frequency, but Na+ channels were only partially distributed within the AIS. Shortly after hearing onset, Na+ channels accumulated along the entire AIS, which started shortening and relocating distally to a larger extent in neurons with higher tuning frequencies. Ablation of inner ears abolished the shortening of the AIS without affecting the position of its proximal boundary, indicating that both distal and proximal AIS boundaries are disassembled during development, and the former is dependent on afferent activity. Thus, interaction of these activity-dependent and activity-independent mechanisms determines the cell-specific distribution of the AIS in NL neurons and plays a critical role in establishing the function of sound localization circuit.
authors.affiliation: Department of Cell Physiology, Nagoya University, Graduate School of Medicine, Nagoya 466-8550, Japan, JST, PRESTO, Saitama 332-0012, Japan, and Department of Physiology and Neurobiology, Faculty of Medicine, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kuba
authors.forename: Ryota
authors.initials: R
authors.lastname: Adachi
authors.forename: Harunori
authors.initials: H
authors.lastname: Ohmori
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D017487:Ankyrins / Q000378:metabolism; D001306:Auditory Pathways / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D001369:Axons / Q000502:physiology*; D002642:Chick Embryo; D002645:Chickens; D017626:Cochlear Nucleus / Q000166:cytology / Q000196:embryology / Q000254:growth & development; D003198:Computer Simulation; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D008959:Models, Neurological; D018992:Myelin-Associated Glycoprotein / Q000378:metabolism; D062551:NAV1.2 Voltage-Gated Sodium Channel / Q000378:metabolism; D009474:Neurons / Q000166:cytology*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism
chemical_list: D017487:Ankyrins; D018992:Myelin-Associated Glycoprotein; D062551:NAV1.2 Voltage-Gated Sodium Channel; D010751:Phosphopyruvate Hydratase
keywords: action potential; ankyrinG; auditory; axon initial segment; nucleus laminaris; sodium channel