In newborn mammals, the growth of cerebral microvascular networks occurs concurrently with neuronal growth in the brain. Here, Christina Whiteus and her colleagues identify in mice the first direct link between neural activity and microvascular plasticity, demonstrating that overstimulation of neurons in early life results in a near arrest in angiogenesis (Nature doi:10.1038/nature12821, 2014).

Chronic neuronal stimulation by exposure to diverse sounds or repetitive whisker stimulation in neonatal mice—but not adult animals—caused a robust reduction in branching and length of vessels in the region of the brain stimulated. The decrease in vascular density was due to reduced proliferation of endothelial cells and impaired vessel sprouting, and it resulted in lack of appropriate oxygenation of the tissue linked to a decrease in neural spine density. Notably, these changes persisted after cessation of overstimulation and were maintained into adulthood. Using mutant mice with a lack-of-function mutation in nitric oxide synthase (NOS) and wild-type mice treated with NOS inhibitors, the authors found that the reduced vascularization was linked to overproduction of nitric oxide by the hyperactive brain cells.

Because neural overstimulation caused by inducing seizures in the neonatal mice also reduced vascularization, the findings suggest that seizure episodes or overstimulation in infants might increase the vulnerability of the brain and potentially predispose to certain pathologies in adulthood.