5 1Kings College London, London, England, GBR 2King's College London, London, England, GBR 3Guy's and St Thomas's NHS Trust, London, England, GBR 4Guy's and St Thoma's NHS Trust and Wolfson CARD, King's College London, London, England, GBR 5Headache Centre, Guy's and St Thomas' NHS Trust, and Wolfson CARD, King's College London, Barnet, England, GBRīackground: Migraine pathophysiology, with or without aura, has been shown to involve altered cortical activity. FHM02 Effects of Subthreshold Single Pulse Transcranial Magnetic Stimulation (sTMS) on Cortical Excitability Relevant to Migraine Lloyd, J.O. The occurrence of plumes in both a genetic and a physiological model of migraine suggests a broader relevance to the disorder, though further work is needed to understand the mechanism and extent of these events. This shows plumes are not isolated to a genetic form of migraine and may be a more general physiological feature of migraine with aura.Ĭonclusion: Glutamate imaging confirms the FHM2 mutation alters glutamate signaling during cortical processing and uncovers a non-canonical form of glutamate release in FHM2 and CSD. Interestingly, CSD is a potent inducer of plumes in both FHM2 and WT mice, and plumes persist in WT following CSD.
Plumes can be pharmacologically induced in WT by inhibiting glutamate transporter function, suggesting they are due to impaired astrocyte function in FHM2. Indeed, plumes do not require neural action potentials, though they are affected by i signaling. At a mesoscale perspective, whisker mediated glutamate release occurs broadly across the barrel cortex, while glutamatergic plumes are more focal events that do not correlate with whisker stimulation, suggesting their occurrence may be due to alternative mechanisms. Glutamatergic plumes rarely occur in WT during baseline recordings and have not been reported in the literature. In addition, we observed non-canonical glutamate events in FHM2 mice that we have termed glutamatergic plumes, because these longer-duration events appear to diffuse from a central source. Results: Following whisker stimulation, FHM2 mice show a slowed clearance rate of glutamate within the barrel cortex compared to WT littermates, confirming the FHM2 mutation is sufficient to disrupt classic forms of glutamate signaling during sensory processing. Pharmacological manipulations were performed to elucidate potential mechanisms of disrupted glutamate signaling. Glutamate recordings were performed in real time using a fluorescent indicator of extracellular glutamate (iGluSnFR) in combination with epifluorescence and two-photon imaging. Methods: We recorded glutamate fluorescence during sensory processing and e induced CSD in awake, behaving FHM2 mice and wild type (WT) littermates. This study seeks to better understand how glutamate signaling is disrupted in migraine. The depolarizing wave of CSD includes a massive release of glutamate into the extracellular space. Distinct genetic mutations found in familial hemiplegic migraine (FHM) types 1 and 2 both point to disruption in glutamatergic signaling. While no single model captures the entirety of migraine, common features across models have the potential to build a more complete understanding of the disorder. 2 1University of Utah, Salt Lake City, UT, USA 2University of Utah, Salt lake city, UT, USAīackground: Animal models harboring gene mutations found in patients with migraine help direct scientific investigation, while the study of physiological events, such as cortical spreading depression (CSD), provide more general insight into migraine with aura. FHM01 Disruptions of Awake Glutamate Signaling in Two Models of Migraine Parker, P.
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