What does local functional hyperemia tell about local neuronal activation?

In the brain, neuronal activation triggers a local increase in cerebral blood flow, a response named functional hyperemia. The extent to which functional hyperemia faithfully reports brain activation, spatially or temporally, remains a matter of debate. Here, we used the olfactory bulb glomerulus as a neurovascular model and two-photon microscopy imaging to investigate the correlation between calcium signals in glutamatergic terminals of olfactory sensory neurons and local vascular responses. We find that, depending on odor stimulation intensity, vascular responses are differently coupled to calcium signals. Upon moderate odor stimulation, glomerular vascular responses increase accordingly with calcium signals. In contrast, in silent glomeruli neighboring strongly activated ones and in glomeruli adapting upon high odor stimulation, vascular responses are independent of or negatively coupled to presynaptic calcium signals, respectively. Hence, functional hyperemia, a key signal used in functional imaging, can be, at times, an unreliable marker of local brain activation.