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Abstract

BOLD fMRI has been wildly used for mapping brain activity, but the cellular contribution of
BOLD signals is still controversial. In this study, we investigated the correlation between
neuronal/astrocytic calcium and the BOLD signal using simultaneous GCaMP-mediated calcium
and BOLD signal recording, in the event-related state and in resting state, in anesthetized
and in free-moving rats. To our knowledge, the results provide the first demonstration that
evoked and intrinsic astrocytic calcium signals could occur concurrently accompanied by
opposite BOLD signals which are associated with vasodilation and vasoconstriction. We show
that the intrinsic astrocytic calcium is involved in brain state changes and is related to the
activation of central thalamus. First, by simultaneous LFP and fiber optic calcium recording, the
results show that the coupling between LFP and calcium indicates that neuronal activity is the
basis of the calcium signal in both neurons and astrocytes. Second, we found that evoked
neuronal and astrocytic calcium signals are always positively correlated with BOLD responses.
However, intrinsic astrocytic calcium signals are accompanied by the activation of the central
thalamus followed by a striking negative BOLD signal in cortex, which suggests that central
thalamus may be involved in the initiation of the intrinsic astrocytic calcium signal. Third, we
confirmed that the intrinsic astrocytic calcium signal is preserved in free moving rats. Moreover,
the occurrences of intrinsic astrocytic calcium spikes are coincident with the transition between
different sleep stages, which suggests intrinsic astrocytic calcium spikes reflect brain state
transitions. These results demonstrate that the correlation between astrocytic calcium and fMRI
signals is related to the thalamic regulation of cortical states. On the other hand, by studying
the relationship between vessel–specific BOLD signals and spontaneous calcium activity from
adjacent neurons, we show that low frequency spontaneous neuronal activity is the cellular
mechanism of the BOLD signal during resting state.