Neurovascular interactions are essential for proper brain function. While the effect of neural activity oncerebral blood flow has been extensively studied, whether or not neural activity influences vascular patterning remains elusive. Here, we demonstrate that neural activity promotes the formation of vascular networks in the early postnatal mouse barrel cortex. Using a combination of genetics, imaging, and computational tools to allow simultaneous analysis of neuronal and vascular components, we found that vascular density and branching were decreased in the barrel cortex when sensory input was reduced by either a complete deafferentation, a genetic impairment of neurotransmitter release at thalamocortical synapses, or a selective reduction of sensory-related neural activity by whisker plucking. In contrast, enhancement of neural activity by whisker stimulation led to an increase in vascular density and branching. The finding that neural activity is necessary and sufficient to trigger alterations ofvascular networks reveals an important feature of neurovascular interactions.
Bibliographical noteFunding Information:
We thank Drs. Christopher Harvey and Jonathan Cohen, and members of the Gu laboratory, for constructive comments on the manuscript; Dr. Susan Dymecki for providing the Slc6a4-Cre mouse; Drs. Lisa Goodrich and Bernardo Sabatini for sharing their lab equipment; the Neurobiology Imaging Facility in the department of Neurobiology at Harvard Medical School (facility supported in part by the Neural Imaging Center as part of an NINDS P30 Core Center grant #NS072030) and the Enhanced Neuroimaging Core at Harvard NeuroDiscovery Center for helping with confocal imaging; and Lydia Bickford for technical assistance. This work was supported by the Mahoney postdoctoral fellowship (B.L.), the Goldenson and Lefler postdoctoral fellowships (A.B.Z), by FAPESP grant 2011/22639-8 (C.H.C.), FAPESP grant 11/50761-2, CNPQ grant 304351/2009-1 (L.d.F.C.), grant K01DA029044 from NIH/NIDA (P.S.K.), and by the following grants to C.G.: Harvard/MIT Joint Research Grants Program in Basic Neuroscience, Sloan research fellowship, the Genise Goldenson fund, the Freudenberger award, and NIH grant R01NS064583.
© 2014 Elsevier Inc.