Vascular Compartmentalization of Functional Hyperemia from the Synapse to the Pia

Functional hyperemia, a regional increase of blood flow triggered by local neural activation, is used to map brain activity in health and disease. However, the spatial-temporal dynamics of functional hyperemia remain unclear. Two-photon imaging of the entire vascular arbor in NG2-creERT2;GCaMP6f mice shows that local synaptic activation, measured via oligodendrocyte precursor cell (OPC) Ca2+ signaling, generates a synchronous Ca2+ drop in pericytes and smooth muscle cells (SMCs) enwrapping all upstream vessels feeding the activated synapses. Surprisingly, the onset timing, direction, and amplitude of vessel diameter and blood velocity changes vary dramatically from juxta-synaptic capillaries back to the pial arteriole. These results establish a precise spatial-temporal sequence of vascular changes triggered by neural activity and essential for the interpretation of blood-flow-based imaging techniques such as BOLD-fMRI. •Odor triggers rapid Ca2+ elevations in OPC process that are input specific•All pericyte subtypes and SMCs respond to downstream synaptic activation•Synchronous mural cell activation is associated with heterogeneous local hemodynamics•The arteriole and first-order capillary dilate first and form the primary functional unit Rungta et al. perform in vivo two-photon calcium imaging of neuron, oligodendrocyte precursor cell, pericyte, and smooth muscle cell responses to olfactory sensory stimulation in combination with vessel diameter and red blood cell velocity measurements along the entire vascular arbor.