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Article

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

1
Department of Brain and Behavioral Sciences, University of Pavia, 27100 Pavia, Italy
2
IRCCS Mondino Foundation, 27100 Pavia, Italy
3
Department of Molecular Medicine, University of Pavia, 27100 Pavia, Italy
4
NMR Research Unit, Queen Square MS Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London WC1N3 BG, UK
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
These authors contributed equally to this work.
Academic Editor: Jessica Filosa
Cells 2022, 11(6), 1047; https://doi.org/10.3390/cells11061047
Received: 8 February 2022 / Revised: 11 March 2022 / Accepted: 17 March 2022 / Published: 19 March 2022
(This article belongs to the Section Cells of the Nervous System)
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. View Full-Text
Keywords: cerebellum; neurovascular coupling; granule cells; nitric oxide; NMDA receptor cerebellum; neurovascular coupling; granule cells; nitric oxide; NMDA receptor
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MDPI and ACS Style

Gagliano, G.; Monteverdi, A.; Casali, S.; Laforenza, U.; Gandini Wheeler-Kingshott, C.A.M.; D’Angelo, E.; Mapelli, L. Non-Linear Frequency Dependence of Neurovascular Coupling in the Cerebellar Cortex Implies Vasodilation–Vasoconstriction Competition. Cells 2022, 11, 1047. https://doi.org/10.3390/cells11061047

AMA Style

Gagliano G, Monteverdi A, Casali S, Laforenza U, Gandini Wheeler-Kingshott CAM, D’Angelo E, Mapelli L. Non-Linear Frequency Dependence of Neurovascular Coupling in the Cerebellar Cortex Implies Vasodilation–Vasoconstriction Competition. Cells. 2022; 11(6):1047. https://doi.org/10.3390/cells11061047

Chicago/Turabian Style

Gagliano, Giuseppe, Anita Monteverdi, Stefano Casali, Umberto Laforenza, Claudia A.M. Gandini Wheeler-Kingshott, Egidio D’Angelo, and Lisa Mapelli. 2022. "Non-Linear Frequency Dependence of Neurovascular Coupling in the Cerebellar Cortex Implies Vasodilation–Vasoconstriction Competition" Cells 11, no. 6: 1047. https://doi.org/10.3390/cells11061047

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