Non-canonical glutamate signaling in a genetic model of migraine with aura

Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved..

Migraine with aura is a common but poorly understood sensory circuit disorder. Monogenic models allow an opportunity to investigate its mechanisms, including spreading depolarization (SD), the phenomenon underlying migraine aura. Using fluorescent glutamate imaging, we show that awake mice carrying a familial hemiplegic migraine type 2 (FHM2) mutation have slower clearance during sensory processing, as well as previously undescribed spontaneous "plumes" of glutamate. Glutamatergic plumes overlapped anatomically with a reduced density of GLT-1a-positive astrocyte processes and were mimicked in wild-type animals by inhibiting glutamate clearance. Plume pharmacology and plume-like neural Ca2+ events were consistent with action-potential-independent spontaneous glutamate release, suggesting plumes are a consequence of inefficient clearance following synaptic release. Importantly, a rise in basal glutamate and plume frequency predicted the onset of SD in both FHM2 and wild-type mice, providing a novel mechanism in migraine with aura and, by extension, the other neurological disorders where SD occurs.

Errataetall:

CommentIn: Neuron. 2021 Feb 17;109(4):563-565. - PMID 33600751

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:109

Enthalten in:

Neuron - 109(2021), 4 vom: 17. Feb., Seite 611-628.e8

Sprache:

Englisch

Beteiligte Personen:

Parker, Patrick D [VerfasserIn]
Suryavanshi, Pratyush [VerfasserIn]
Melone, Marcello [VerfasserIn]
Sawant-Pokam, Punam A [VerfasserIn]
Reinhart, Katelyn M [VerfasserIn]
Kaufmann, Dan [VerfasserIn]
Theriot, Jeremy J [VerfasserIn]
Pugliese, Arianna [VerfasserIn]
Conti, Fiorenzo [VerfasserIn]
Shuttleworth, C William [VerfasserIn]
Pietrobon, Daniela [VerfasserIn]
Brennan, K C [VerfasserIn]

Links:

Volltext

Themen:

3KX376GY7L
Astrocyte
Cortical spreading depression
Familial hemiplegic migraine
Glutamate
Glutamate transporter
Glutamic Acid
IGluSnFR
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Spreading depolarization

Anmerkungen:

Date Completed 10.03.2021

Date Revised 11.02.2024

published: Print-Electronic

CommentIn: Neuron. 2021 Feb 17;109(4):563-565. - PMID 33600751

Citation Status MEDLINE

doi:

10.1016/j.neuron.2020.11.018

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM318862131