Astrocytic Ca²⁺ signals partake in inhibitory neurovascular coupling in a brain state-dependent manner

Abstract

Neurovascular coupling (NVC) modulates cerebral blood flow to match increased metabolic demand during neuronal excitation. Activation of inhibitory interneurons also increase blood flow, but the basis for this inhibitory NVC is unclear. We performed two-photon microscopy in awake mice to examine the correlation between astrocytic Ca2+ and NVC, evoked by activity in either all (VGATIN) or parvalbumin-positive GABAergic interneurons (PVIN). Optogenetic stimulation of VGATIN and PVIN in the somatosensory cortex triggered astrocytic Ca2+ increases that were abolished by anaesthesia. PVIN evoked astrocytic Ca2+ responses with a short latency that preceded NVC, whereas VGATIN evoked Ca2+ increases that were delayed relative to the NVC response. The early onset in PVIN evoked Ca2+ increases dependent on noradrenaline release from locus coeruleus, which also affected inhibitory NVC. Therefore, NVC mechanisms should be studied in awake mice and, though the relationship between interneuron activity and astrocytic Ca2+ is complex, we found a correlation between astrocyte activity and NVC in PVIN.

Deletion of aquaporin‐4 improves capillary blood flow distribution in brain edema

“…We demonstrate a pronounced increase in astrocytic Ca 2+ signaling during edema, which is an important signaling pathway involved in cellular volume regulation, and likely plays a role in the control of capillary flow (Krogsgaard et al, 2022;Mishra et al, 2016). Our findings are consistent with a previous study using synthetic Ca 2+ indicators in anesthetized mice (Thrane et al, 2011).…”

Modulatory Effects of Noradrenergic and Serotonergic Signaling Pathway on Neurovascular Coupling

“…Because astrocytes are nonexcitable cells, their Ca 2+ dynamics have been used as an index of their activity. These Ca 2+ signals have been linked to synaptic plasticity 1,2 and NVC [3][4][5][6][7][8][9] . Moreover, while the critical role of localized synaptic glutamatergic signaling pathways in initiating the NVCmediated increases in local blood flow have been extensively investigated [10][11][12] , the contributions of other neurotransmitters to NVC have received less attention.…”