Action potential processing in a detailed Purkinje cell model reveals a critical role for axonal compartmentalization

Frontiers in Cellular Neuroscience
Stefano MasoliEgidio D'Angelo

Abstract

The Purkinje cell (PC) is among the most complex neurons in the brain and plays a critical role for cerebellar functioning. PCs operate as fast pacemakers modulated by synaptic inputs but can switch from simple spikes to complex bursts and, in some conditions, show bistability. In contrast to original works emphasizing dendritic Ca-dependent mechanisms, recent experiments have supported a primary role for axonal Na-dependent processing, which could effectively regulate spike generation and transmission to deep cerebellar nuclei (DCN). In order to account for the numerous ionic mechanisms involved (at present including Nav1.6, Cav2.1, Cav3.1, Cav3.2, Cav3.3, Kv1.1, Kv1.5, Kv3.3, Kv3.4, Kv4.3, KCa1.1, KCa2.2, KCa3.1, Kir2.x, HCN1), we have elaborated a multicompartmental model incorporating available knowledge on localization and gating of PC ionic channels. The axon, including initial segment (AIS) and Ranvier nodes (RNs), proved critical to obtain appropriate pacemaking and firing frequency modulation. Simple spikes initiated in the AIS and protracted discharges were stabilized in the soma through Na-dependent mechanisms, while somato-dendritic Ca channels contributed to sustain pacemaking and to generate complex bursting at hi...Continue Reading

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Citations

Jul 28, 2016·Frontiers in Cellular Neuroscience·Egidio D'AngeloEduardo Ros
Oct 25, 2016·Mathematical Biosciences and Engineering : MBE·Beata Jackowska-Zduniak, Urszula Forys
Sep 15, 2017·Physiological Reviews·Leonard K Kaczmarek, Yalan Zhang
Jun 28, 2019·Frontiers in Computational Neuroscience·Alice GeminianiAlessandra Pedrocchi
Dec 19, 2018·Frontiers in Neuroinformatics·Alice GeminianiEgidio D'Angelo
Nov 27, 2018·Frontiers in Neuroscience·Claudia A M Gandini Wheeler-KingshottEgidio U D'Angelo
Jun 4, 2019·Frontiers in Neuroinformatics·Stefano CasaliEgidio D'Angelo
Jul 17, 2020·International Journal of Molecular Sciences·Hiroshi MitomaMario Manto
Apr 1, 2017·Frontiers in Cellular Neuroscience·Stefano MasoliEgidio D'Angelo
Dec 4, 2019·Frontiers in Molecular Neuroscience·Francesca PrestoriEgidio D'Angelo
Oct 22, 2019·Frontiers in Computational Neuroscience·Alice GeminianiClaudia Casellato
Dec 31, 2020·PLoS Computational Biology·Stefano MasoliEgidio D'Angelo
Jan 15, 2021·Nature Communications·Sebastian R SchreglmannNir Grossman
Feb 18, 2021·Scientific Reports·Martina Francesca RizzaEgidio D'Angelo
Apr 27, 2021·Frontiers in Cellular Neuroscience·Rin KuriyamaTadashi Yamazaki

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