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).
Five recent publications
- Non-canonical glutamate signaling in a genetic model of migraine with aura.
Parker PD, Suryavanshi P, Melone M, Sawant-Pokam PA, Reinhart KM, Kaufmann D, Theriot JJ, Pugliese A, Conti F, Shuttleworth CW, Pietrobon D, Brennan KC. Neuron. 2021; 109(4):611-628.e8. doi: 10.1016/j.neuron.2020.11.018
- Enhanced Thalamocortical Synaptic Transmission and Dysregulation of the Excitatory-Inhibitory Balance at the Thalamocortical Feedforward Inhibitory Microcircuit in a Genetic Mouse Model of Migraine.
Tottene A, Favero M, Pietrobon D. J Neurosci. 2019; 39(49):9841-9851. doi: 10.1523/JNEUROSCI.1840-19.2019
- 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
- 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