Find Paper, Faster
Example:10.1021/acsami.1c06204 or Chem. Rev., 2007, 107, 2411-2502
Non-canonical glutamate signaling in a genetic model of migraine with aura
Neuron  (IF17.173),  Pub Date : 2020-12-14, DOI: 10.1016/j.neuron.2020.11.018
Patrick D. Parker, Pratyush Suryavanshi, Marcello Melone, Punam A. Sawant-Pokam, Katelyn M. Reinhart, Dan Kaufmann, Jeremy J. Theriot, Arianna Pugliese, Fiorenzo Conti, C. William Shuttleworth, Daniela Pietrobon, K.C. Brennan

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.