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

ABSTRACT: 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, su

SUBMITTER: Parker PD 

PROVIDER: S-EPMC7889497 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature