As a mean to advance mechanistic understanding of migraine, the research activity focuses on the investigation of the cellular and circuit mechanisms of the primary brain dysfunctions that cause a rare monogenic form of migraine with aura (familial hemiplegic migraine, FHM), using FHM mouse models. These animal models include knock-in mice carrying FHM type 1 and type 2 mutations in the genes encoding the neuronal voltage-gated calcium channel CaV2.1 and the astrocytic alpha2 Na/K ATPase, respectively.
The experimental approach is to combine experiments in acute cortical slices and in head-fixed awake animals using electrophysiological, imaging and optogenetic techniques to study the brain pathogenic alterations at a multi-scale level (cellular, synaptic, local microcircuit and mesoscale circuit levels).
- Brennan KC and Pietrobon D. A systems Neuroscience approach to migraine. (2018) Neuron 97: 1004-1021
- Capuani C, Melone M, Tottene A, Bragina L, Crivellaro G, Santello M, Casari G, Conti F and Pietrobon D. Defective glutamate and K+ clearance by cortical astrocytes in familial hemiplegic migraine type 2. (2016) EMBO Mol Med. 8:967-986
- Pietrobon D and Moskowitz M. Propagation of chaos and commotion in the wake of cortical spreading depression and spreading depolarizations. (2014) Nature Rev. Neurosci. 15:379-393
- Vecchia D, Tottene A, van den Maagdenberg AM and Pietrobon D. Mechanism underlying unaltered cortical inhibitory synaptic transmission in contrast with enhanced excitatory transmission in CaV2.1 knockin migraine mice (2014) Neurobiol Dis. 69:225-234
- Tottene A, Conti R, Fabbro A, Vecchia D, Shapovalova M, Santello M, van den Maagdenberg AMJM, Ferrari M and Pietrobon D. Enhanced excitatory transmission at cortical synapses as the basis for facilitated spreading depression in CaV2.1 knockin migraine mice. Neuron (2009) 61: 762-773