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Astrocyte dysfunction increases cortical dendritic excitability and promotes cranial pain in familial migraine

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Romanos Jennifer, Benke Dietmar, Pietrobon Daniela, Zeilhofer Hanns Ulrich, Santello Mirko,
Project Cortical mechanisms controlling migraine pain
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Original article (peer-reviewed)

Journal Science Advances
Volume (Issue) 6(23)
Page(s) eaaz1584 - eaaz1584
Title of proceedings Science Advances
DOI 10.1126/sciadv.aaz1584

Open Access

Type of Open Access Publisher (Gold Open Access)


Astrocytes are essential contributors to neuronal function. As a consequence, disturbed astrocyte-neuron interactions are involved in the pathophysiology of several neurological disorders, with a strong impact on brain circuits and behavior. Here, we describe altered cortical physiology in a genetic mouse model of familial hemiplegic migraine type 2 (FHM2), with reduced expression of astrocytic Na + ,K + -ATPases. We used whole-cell electrophysiology, two-photon microscopy, and astrocyte gene rescue to demonstrate that an impairment in astrocytic glutamate uptake promotes NMDA spike generation in dendrites of cingulate cortex pyramidal neurons and enhances output firing of these neurons. Astrocyte compensation of the defective ATPase in the cingulate cortex rescued glutamate uptake, prevented abnormal NMDA spikes, and reduced sensitivity to cranial pain triggers. Together, our results demonstrate that impaired astrocyte function alters neuronal activity in the cingulate cortex and facilitates migraine-like cranial pain states in a mouse model of migraine.