title: Covariation of axon initial segment location and dendritic tree normalizes the somatic action potential.
abstract: In mammalian neurons, the axon initial segment (AIS) electrically connects the somatodendritic compartment with the axon and converts the incoming synaptic voltage changes into a temporally precise action potential (AP) output code. Although axons often emanate directly from the soma, they may also originate more distally from a dendrite, the implications of which are not well-understood. Here, we show that one-third of the thick-tufted layer 5 pyramidal neurons have an axon originating from a dendrite and are characterized by a reduced dendritic complexity and thinner main apical dendrite. Unexpectedly, the rising phase of somatic APs is electrically indistinguishable between neurons with a somatic or a dendritic axon origin. Cable analysis of the neurons indicated that the axonal axial current is inversely proportional to the AIS distance, denoting the path length between the soma and the start of the AIS, and to produce invariant somatic APs, it must scale with the local somatodendritic capacitance. In agreement, AIS distance inversely correlates with the apical dendrite diameter, and model simulations confirmed that the covariation suffices to normalize the somatic AP waveform. Therefore, in pyramidal neurons, the AIS location is finely tuned with the somatodendritic capacitive load, serving as a homeostatic regulation of the somatic AP in the face of diverse neuronal morphologies.
authors.affiliation: Department of Axonal Signaling, Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences (KNAW), 1105 BA Amsterdam, The Netherlands.|Cell Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, The Netherlands.
authors.forename: Mustafa S
authors.initials: MS
authors.lastname: Hamada
authors.affiliation: Sorbonne Universités, Université Pierre et Marie Curie (UPMC) Univ Paris 06, INSERM, CNRS, Institut de la Vision, 75012 Paris, France.
authors.forename: Sarah
authors.initials: S
authors.lastname: Goethals
authors.affiliation: Department of Axonal Signaling, Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences (KNAW), 1105 BA Amsterdam, The Netherlands.
authors.forename: Sharon I
authors.initials: SI
authors.lastname: de Vries
authors.affiliation: Sorbonne Universités, Université Pierre et Marie Curie (UPMC) Univ Paris 06, INSERM, CNRS, Institut de la Vision, 75012 Paris, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Brette
authors.affiliation: Department of Axonal Signaling, Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences (KNAW), 1105 BA Amsterdam, The Netherlands; m.kole@nin.knaw.nl.|Cell Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, The Netherlands.
authors.forename: Maarten H P
authors.identifier: 0000-0002-3883-5682
authors.initials: MH
authors.lastname: Kole
mesh_terms: D000200:Action Potentials; D000818:Animals; D000071040:Axon Initial Segment / Q000502:physiology*; D001369:Axons / Q000502:physiology*; D003198:Computer Simulation; D003712:Dendrites / Q000502:physiology*; D004594:Electrophysiology; D005260:Female; D006706:Homeostasis; D008297:Male; D009474:Neurons / Q000502:physiology; D017966:Pyramidal Cells / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000502:physiology
keywords: action potential; axon; axon initial segment; computational model; dendrites