Purkinje Cell Signaling Deficits in Animal Models of Ataxia

Frontiers in Synaptic Neuroscience
Eriola HoxhaFilippo Tempia

Abstract

Purkinje cell (PC) dysfunction or degeneration is the most frequent finding in animal models with ataxic symptoms. Mutations affecting intrinsic membrane properties can lead to ataxia by altering the firing rate of PCs or their firing pattern. However, the relationship between specific firing alterations and motor symptoms is not yet clear, and in some cases PC dysfunction precedes the onset of ataxic signs. Moreover, a great variety of ionic and synaptic mechanisms can affect PC signaling, resulting in different features of motor dysfunction. Mutations affecting Na+ channels (NaV1.1, NaV1.6, NaVβ4, Fgf14 or Rer1) reduce the firing rate of PCs, mainly via an impairment of the Na+ resurgent current. Mutations that reduce Kv3 currents limit the firing rate frequency range. Mutations of Kv1 channels act mainly on inhibitory interneurons, generating excessive GABAergic signaling onto PCs, resulting in episodic ataxia. Kv4.3 mutations are responsible for a complex syndrome with several neurologic dysfunctions including ataxia. Mutations of either Cav or BK channels have similar consequences, consisting in a disruption of the firing pattern of PCs, with loss of precision, leading to ataxia. Another category of pathogenic mechanisms o...Continue Reading

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Citations

Aug 14, 2019·Annals of Clinical and Translational Neurology·Jaya PunethaJames R Lupski
Jan 2, 2020·International Journal of Molecular Sciences·Francesca PrestoriEgidio D'Angelo
Mar 18, 2020·International Journal of Molecular Sciences·Alberto BenussiBarbara Borroni
Sep 24, 2020·Expert Opinion on Therapeutic Targets·Andreia Neves-CarvalhoPatrícia Maciel
Sep 17, 2020·International Journal of Molecular Sciences·Aleksandar ArsovićGeorg Auburger
Jun 26, 2020·Frontiers in Neuroscience·Anna Niewiadomska-CimickaYvon Trottier
Sep 10, 2020·International Journal of Molecular Sciences·Rocío Alfaro-RuízRafael Luján
Aug 9, 2020·Frontiers in Neuroscience·Katherine J RobinsonAngela S Laird
Dec 14, 2018·Frontiers in Aging Neuroscience·Eriola HoxhaMaria Concetta Miniaci
Dec 26, 2019·Pflügers Archiv : European journal of physiology·Yang XuTing-Hua Wang
Dec 18, 2020·Frontiers in Cellular Neuroscience·Isis Zhang, Huijuan Hu
Feb 13, 2021·Neurology. Genetics·Martin PaucarPer Svenningsson
Nov 12, 2020·Journal of Neuroscience Research·Pellegrino LippielloMaria Concetta Miniaci
Mar 30, 2021·Frontiers in Aging Neuroscience·Jennifer C MiguelElliott J Mufson
May 1, 2021·Cells·Ana Quelle-RegaldieLaura Sánchez

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Methods Mentioned

BETA
footprinting
antisense nucleotides

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