Neurovascular coupling in hippocampus is mediated via diffusion by neuronal-derived nitric oxide.

The coupling between neuronal activity and cerebral blood flow (CBF) is essential for normal brain function. The mechanisms behind this neurovascular coupling process remain elusive, mainly because of difficulties in probing dynamically the functional and coordinated interaction between neurons and the vasculature in vivo. Direct and simultaneous measurements of nitric oxide (NO) dynamics and CBF changes in hippocampus in vivo support the notion that during glutamatergic activation nNOS-derived NO induces a time-, space-, and amplitude-coupled increase in the local CBF, later followed by a transient increase in local O2 tension. These events are dependent on the activation of the NMDA-glutamate receptor and nNOS, without a significant contribution of endothelial-derived NO or astrocyte-neuron signaling pathways. Upon diffusion of NO from active neurons, the vascular response encompasses the activation of soluble guanylate cyclase. Hence, in the hippocampus, neurovascular coupling is mediated by nNOS-derived NO via a diffusional connection between active glutamatergic neurons and blood vessels.