ArticleAnnals of neurology2015
Abnormal synaptic Ca(2+) homeostasis and morphology in cortical neurons of familial hemiplegic migraine type 1 mutant mice.
Article in Annals of neurology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 44 citations in OpenAlex.
- Hemiplegic migraine: genetics and pathophysiology.The Journal of clinical investigation · 2026Review
- From bench to bedside: relevant animal models across the migraine attack phases.The journal of headache and pain · 2026Review
- Tsunamis hiding in plain sight: spreading depression in clinical neurology.Nature reviews. Neurology · 2026Review
- Is canonical SD a clinically relevant model of migraine? Argument pro.The journal of headache and pain · 2025Review
- Spreading depolarization as a therapeutic target in migraine.Nature reviews. Neurology · 2025Review
- Genetic influence of the brain imaging phenotypes, brain and cerebrospinal fluid metabolites and brain genes on migraine subtypes: a Mendelian randomization and multi-omics study.The journal of headache and pain · 2025Article
- Unraveling the interplay of neuroinflammatory signaling between parenchymal and meningeal cells in migraine headache.The journal of headache and pain · 2024Review
- PACAP-PAC1 receptor inhibition is effective in opioid induced hyperalgesia and medication overuse headache models.iScience · 2023Article
- Parenchymal neuroinflammatory signaling and dural neurogenic inflammation in migraine.The journal of headache and pain · 2021Review
- Structural and Functional Brain Changes in Migraine.Pain and therapy · 2021Review
- Neuronal complexity is attenuated in preclinical models of migraine and restored by HDAC6 inhibition.eLife · 2021Article
- Article
- NaJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2020Article
- Current understanding of cortical structure and function in migraine.Cephalalgia : an international journal of headache · 2019Review
- Relief Following Chronic Stress Augments Spreading Depolarization Susceptibility in Familial Hemiplegic Migraine Mice.Neuroscience · 2019Article
- Genetic mouse models of migraine.The journal of headache and pain · 2019Review
- Aura and Stroke: relationship and what we have learnt from preclinical models.The journal of headache and pain · 2019Review
- Mouse Models of Familial Hemiplegic Migraine for Studying Migraine Pathophysiology.Current neuropharmacology · 2019Review
- Drosophila CaV2 channels harboring human migraine mutations cause synapse hyperexcitability that can be suppressed by inhibition of a Ca2+ store release pathway.PLoS genetics · 2018Article
- Lipidomic analysis of serum samples from migraine patients.Lipids in health and disease · 2018Article
Corrections and comments
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Authors and funding
19 authors at 3 institutions in 2 countries.
Funding
Abstract
objectiveMigraine is among the most common and debilitating neurological conditions. Familial hemiplegic migraine type 1 (FHM1), a monogenic migraine subtype, is caused by gain-of-function of voltage-gated CaV 2.1 calcium channels. FHM1 mice carry human pathogenic mutations in the α1A subunit of CaV 2.1 channels and are highly susceptible to cortical spreading depression (CSD), the electrophysiologic event underlying migraine aura. To date, however, the mechanism underlying increased CSD/migraine susceptibility remains unclear.
methodsWe employed in vivo multiphoton microscopy of the genetically encoded Ca(2+)-indicator yellow cameleon to investigate synaptic morphology and [Ca(2+)]i in FHM1 mice. To study CSD-induced cerebral oligemia, we used in vivo laser speckle flowmetry and multimodal imaging. With electrophysiologic recordings, we investigated the effect of the CaV 2.1 gating modifier tert-butyl dihydroquinone on CSD in vivo.
resultsFHM1 mutations elevate neuronal [Ca(2+)]i and alter synaptic morphology as a mechanism for enhanced CSD susceptibility that we were able to normalize with a CaV 2.1 gating modifier in hyperexcitable FHM1 mice. At the synaptic level, axonal boutons were larger, and dendritic spines were predominantly of the mushroom type, which both provide a structural correlate for enhanced neuronal excitability. Resting neuronal [Ca(2+)]i was elevated in FHM1, with loss of compartmentalization between synapses and neuronal shafts. The percentage of calcium-overloaded neurons was increased. Neuronal [Ca(2+)]i surge during CSD was faster and larger, and post-CSD oligemia and hemoglobin desaturation were more severe in FHM1 brains.
interpretationOur findings provide a mechanism for enhanced CSD susceptibility in hemiplegic migraine. Abnormal synaptic Ca(2+) homeostasis and morphology may contribute to chronic neurodegenerative changes as well as enhanced vulnerability to ischemia in migraineurs.
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