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 |
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Medienart: |
E-Artikel |
Erscheinungsjahr: |
2021 |
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Erschienen: |
2021 |
Enthalten in: |
Zur Gesamtaufnahme - volume:109 |
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Enthalten in: |
Neuron - 109(2021), 4 vom: 17. Feb., Seite 611-628.e8 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Parker, Patrick D [VerfasserIn] |
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Links: |
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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 |
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doi: |
10.1016/j.neuron.2020.11.018 |
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funding: |
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PPN (Katalog-ID): |
NLM318862131 |
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520 | |a Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved. | ||
520 | |a 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 | ||
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