Neurovascular coupling at the cerebellar granular layer

The tight coupling between local neuronal activity and local cerebral blood flow, or neurovascular coupling (NVC), originates the blood-oxygen-level-dependent (BOLD) signals used by neuroimaging techniques to map changes in brain activity. In the cerebellum, the NVC has been investigated in the molecular layer, showing poor association with the spiking activity of Purkinje cells, which represent the sole output of the cerebellar cortex. Conversely, at the present no information is available about the control of microvascular tone in the granular layer, at the input stage of the cerebellum. This is surprising since granule cells (GrCs) are the most abundant brain neurons and produce nitric oxide (NO) in response to mossy fibers (MF) stimulation. Therefore, herein we exploited bright-field microscopy on rat cerebellar acute slices to assess whether and how the MF-GrC relay controls arteriole (10-20 µm) diameter. MF bundles were electrically stimulated with 30 sec 50Hz train pulses, which induced a 20% vasodilation in a NMDA- and NO-dependent manner. Vasodilation was turned into vasoconstriction by preventing NO production. This switch proved to be dependent on the vasoconstrictor 20-hydroxyeicosatetraenoic acid, whose synthesis is blocked in the presence of NO. Overall, these data strongly suggest that synaptic activation of GrCs causes arteriolar vasodilation that is likely to contribute to cerebellar BOLD signals. In the light of the NO-dependence of MF-GrC synaptic plasticity, it would be intriguing to investigate the NVC during neuronal plasticity