Study of a role of astrocyte Ca2+ in functional hyperemia in awake mouse model

Title: Astrocytes amplify neurovascular coupling to sustained activation of neocortex in awake mice

Journal: Nat Commun (2022) 13:7872​

Link: https://www.nature.com/articles/s41467-022-35383-2

Comments:

Neurons need blood to supply O2 and glucose to perform normal physiological functions. Therefore, when neurons process sensory information it causes an increase in regional cerebral blood flow (CBF) called functional hyperemia. Functional hyperemia shows a bimodal response including early and late phases in awake mouse. However, the cellular mechanisms, in which neurons, astrocytes, and endothelial cells are involved, underlying the distinct phases are still unknown.

When functional hyperemia was induced by whisker stimulation, penetrating arteriole diameter and change in Ca2+ signals of astrocytes were monitored by 2-photon microscopy. By comparing brief (5s) with sustained (30s) stimulation, the bimodal dilation of arteriole in response to sensory stimulation occurred with the change in astrocyte Ca2+.

In order to investigate the specific effects of astrocyte Ca2+ on functional hyperemia，CalEx that is Ca2+ ATPase pump was used as astrocyte Ca2+ silencing tool. Compared with control group, their result indicates that astrocyte Ca2+ is important for amplifying arteriole dilation during sustained functional hyperemia. Gq-DREADD was used as another tool to mediating astrocyte Ca2+ . DREADD agonist application affected arteriole dilation only in the late phase of sustained functional hyperemia.​

In the functional hyperemia model, rapid vasodilation depends on N-methyl-D-aspartate receptors (NMDAR)-dependent nitric oxide. Combined with NMDAR antagonist decreased astrocytes Ca2+ transient around penetrators and dilation of arteriole in the late phase, suggesting that NMDARs are critical for astrocyte Ca 2+ elevation and for the late phase.

Astrocyte Ca2+ plays a key role in prolonging functional hyperemia during neuronal activation by amplifying functional hyperemia. This study can further help us understand the normal physiological function of astrocytes.