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

ABSTRACT: 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 glutam

SUBMITTER: Romanos J 

PROVIDER: S-EPMC7274778 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature