A New Form of Glutamate Signaling Discovered in Migraine

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.