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

Abstract

Summary: 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. : Using concomitant multimodality optical imaging of synchronized neuronal or astrocytic Ca2+ and hemodynamic changes, Gu et al. show hemodynamic responses to slow sensory stimuli without astrocytic Ca2+ changes. Astrocytic Ca2+ correlates with vasoconstriction after fast stimuli. Neuronal, not astrocytic, slow Ca2+ fluctuations correlate with hemodynamics at rest. Keywords: astrocyte, neurovascular coupling, neuron, GCaMP6f, astrocytic Ca2+ fluctuation, synchronized astrocyte responses, somatosensory stimulation, resting state, low-frequency oscillations, synchronized neuronal responses