Non-Linear Frequency Dependence of Neurovascular Coupling in the Cerebellar Cortex Implies Vasodilation–Vasoconstriction Competition

Neurovascular coupling (NVC) is the process associating local cerebral blood flow (CBF)
to neuronal activity (NA). Although NVC provides the basis for the blood oxygen level dependent
(BOLD) effect used in functional MRI (fMRI), the relationship between NVC and NA is still unclear.
Since recent studies reported cerebellar non-linearities in BOLD signals during motor tasks execution,
we investigated the NVC/NA relationship using a range of input frequencies in acute mouse
cerebellar slices of vermis and hemisphere. The capillary diameter increased in response to mossy
fiber activation in the 6–300 Hz range, with a marked inflection around 50 Hz (vermis) and 100 Hz
(hemisphere). The corresponding NA was recorded using high-density multi-electrode arrays and
correlated to capillary dynamics through a computational model dissecting the main components
of granular layer activity. Here, NVC is known to involve a balance between the NMDAR-NO
pathway driving vasodilation and the mGluRs-20HETE pathway driving vasoconstriction. Simulations
showed that the NMDAR-mediated component of NA was sufficient to explain the time
course of the capillary dilation but not its non-linear frequency dependence, suggesting that the
mGluRs-20HETE pathway plays a role at intermediate frequencies. These parallel control pathways
imply a vasodilation–vasoconstriction competition hypothesis that could adapt local hemodynamics
at the microscale bearing implications for fMRI signals interpretation.