Astrocytic calcium signal bidirectionally regulated BOLD-fMRI signals in awake mice

Motivation: Previous study found brain-state dependent astrocytic calcium signals are related to positive and negative BOLD-fMRI signals. However, causal evidences regarding the contribution of astrocytes to BOLD signals is lacking. Goal(s): We aimed to provide causal evidences for the bidirectional contribution of astrocytic calcium activity on BOLD-fMRI signals. Approach: We applied simultaneous calcium imaging and awake mouse fMRI to detect distinct astrocytic signals (task-aligned vs. spontaneous) coupled to BOLD signals in three conditions, including no manipulation, activation and inhibition of S1BF astrocytes. Results: We found whisker stimulation-evoked astrocyte activity mainly contributes to positive BOLD signals, while state-specific astrocyte activity contributes to negative BOLD signals. Impact: We provide casual evidences that astrocytes bidirectionally regulated BOLD signals. Moreover, our results challenge the prevailing interpretation of the BOLD signal solely as an indicator of neuronal activity by highlighting the impact of arousal-specific involvement of astrocytes in neurovascular coupling.