Synchronized Astrocytic Ca2+ Responses in Neurovascular Coupling during Somatosensory Stimulation and for the Resting State

Abstract

The role of astrocytes in neurovascular coupling (NVC) is unclear. Here, we applied a multimodality imaging approach to concomitantly measure synchronized neuronal or astrocytic Ca²⁺ and hemodynamic changes in the mouse somatosensory cortex at rest and during sensory electrical stimulation. Strikingly, we found that low-frequency stimulation (0.3-1 Hz), which consistently evokes fast neuronal Ca²⁺ transients (6.0 ± 2.7 ms latency) that always precede vascular responses, does not always elicit astrocytic Ca²⁺ transients (313 ± 65 ms latency). However, the magnitude of the hemodynamic response is increased when astrocytic transients occur, suggesting a facilitatory role of astrocytes in NVC. High-frequency stimulation (5-10 Hz) consistently evokes a large, delayed astrocytic Ca²⁺ accumulation (3.48 ± 0.09 s latency) that is temporarily associated with vasoconstriction, suggesting a role for astrocytes in resetting NVC. At rest, neuronal, but not astrocytic, Ca²⁺ fluctuations correlate with hemodynamic low-frequency oscillations. Taken together, these results support a role for astrocytes in modulating, but not triggering, NVC.

Keywords: GCaMP6f; astrocyte; astrocytic Ca(2+) fluctuation; low-frequency oscillations; neuron; neurovascular coupling; resting state; somatosensory stimulation; synchronized astrocyte responses; synchronized neuronal responses.