A New Form of Glutamate Signaling Discovered in Migraine

Graphic- A New Form of Glutamate Signaling Discovered in Migraine
A) Plumes result from an imbalance between release of glutamate from neurons and its reuptake by astrocytes. B) Plumes occur both during initiation (left) and propagation (right) of spreading depolarizations (SD), waves of excitation that occur in multiple neurologic diseases.

Migraine is a disorder of the sensory nervous system, consisting of head pain and debilitating sensory amplifications, wherein the normal senses we use in daily living become painful.  Although migraine is thought to be the result of increased nervous system excitability, the actual mechanisms are poorly understood.  Using two-photon microscopy, K.C. Brennan, MD, and colleagues discovered unusual activity of the excitatory neurotransmitter glutamate in mice carrying a mutated gene identified from a family with inherited migraine. These ‘plumes’ of glutamate release were much more common in mice carrying the migraine mutation than in those without.  Moreover, a flurry of plume events preceded spreading depolarizations, massive waves of excitation that cause the migraine aura.  This novel finding is important beyond migraine, because spreading depolarizations occur in several other conditions, including stroke and traumatic brain injury. Thus, plumes represent a novel mechanism of excitability in the brain, relevant to a broad array of neurologic diseases.

References:

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Non-canonical glutamate signaling in a genetic model of migraine with aura. Parker PD, Suryavanshi PS, Melone M, Sawant-Pokam PM, Reinhart KM, Kaufmann D, Theriot JJ, Pugliese A, Conti F, Shuttleworth CW, Pietrobon D, Brennan KC. Neuron.2021 Feb 17;109(4):611.e8. PMID: 33321071. 

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U of U Key Faculty Collaborators

Punam Sawant-Pokam, PhD
Dan Kaufmann, PhD