News



Read our new paper on neurovascular mechanisms!
 

Neurons in the brain rely on blood vessels for supply of oxygen and sugar. A change in neuronal activity leads to vasodilation or vasoconstriction of cerebral arteries and arterioles so that supply meets demand. This phenomenon is exploited in a noninvasive brain imaging technique called functional magnetic resonance imaging (fMRI), where active brain areas, which receive extra oxygen, appear highlighted in the image. But how do blood vessels “know” when to dilate or constrict? Understanding the language of communication between neurons and blood vessels would help interpreting fMRI images in terms of the underlying neuronal activity.

Previously, we reported that arteriolar dilation and constriction correlated with neuronal excitation and inhibition, respectively. However, direct evidence that spiking of inhibitory neurons causes vasoconstriction in intact brains is missing. Therefore, in the present study, we asked whether vasoconstriction was specific to activation of the inhibitory rather than excitatory neurons. We used genetically modified mice, in which excitatory or inhibitory neurons can be selectively activated by shining a blue light on the brain surface. In each case, we performed high-resolution microscopic imaging of arterioles in intact cerebral cortex of live mice, and combined the imaging with the blue light-induced neuronal stimulation. Our results demonstrate that both excitatory and inhibitory neurons can drive vasodilation while vasoconstriction is mediated exclusively by the inhibitory neurons. Furthermore, we identify the vasoconstrictive signaling agent as Neuropeptide Y (NPY). NPY is a signaling molecule that is released by a specific sub-type of inhibitory neurons called “NPY-positive neurons.” NPY binds to vascular Y1 receptors causing vasoconstriction. Thus, vasoconstriction and the associated fMRI signals in cerebral cortex under normal physiological conditions may be mainly driven by the NPY-positive inhibitory neurons. The NPY-Y1 signaling mechanism may also offer a potential therapeutic target in cerebrovascular disease.

Further investigation is needed to identify mechanisms responsible for vasodilation. These mechanisms may involve cellular signaling agents, specific ions, and/or bi-products of energy metabolism. Specific fluorescent reporters for these molecules and ions, currently being developed under the BRAIN Initiative, will accelerate our progress towards solving the puzzle of neurovascular communication.