The Nuanced Relationship Between Neuronal Activity and Blood Flow
Post by Shahin Khodaei
The takeaway
Increased neuronal activity in a brain region increases blood flow to that area. When neurons in a region are active, the signal gets sent up along the vessels that supply blood to that region, causing them to dilate upstream.
What's the science?
When there is increased neuronal activity in a region of the brain, more blood flows to that area – a process called neurovascular coupling (NVC). This coupling is the basis for functional magnetic resonance imaging (fMRI), which measures blood flow to a brain region as a surrogate for neuronal activity. The regulation of NVC at the spatial level is not well understood – does increased neuronal activity in a small brain area lead to dilation of blood vessels in the same region? Or is the relationship more nuanced? This week in Nature Neuroscience, Martineau and colleagues addressed these questions by studying neuronal activity and blood vessel dilation in small regions of the mouse brain using microscopy.
How did they do it?
The authors used a mouse model and focused on a brain region called the sensory cortex, which is active in response to physical stimulation. Within the rodent sensory cortex, there are cortical “barrels” which become active in response to stimulation of each of the mouse’s whiskers – a cortical barrel for whisker W1, a barrel for the next whisker W2, then W3, and so on. To study the relationship between neuronal activity and blood flow in the brain of mice, the authors removed a portion of the skull directly over the sensory cortex and surgically replaced it with glass. This gave them a window through which they could study the sensory cortex, using microscopes.
The authors performed their experiments on mice whose neurons expressed a fluorescent calcium indicator, meaning that active neurons emitted red light. They then stimulated the whiskers of mice, and used wide field imaging to locate the corresponding barrel for each whisker. Simultaneously, they made use of the fact that oxygenated and de-oxygenated hemoglobin scatters the microscope’s light differently, and were able to characterize blood flow to each barrel. They also used a very high-resolution technique called two-photon microscopy to study the dilation and blood flow through individual vessels in each barrel, and how it changed due to whisker stimulation and neuronal activity.
What did they find?
As expected, when each whisker was stimulated, the corresponding barrel in the sensory cortex showed increased neuronal activity and increased blood flow. Then the authors used higher resolution imaging techniques to study blood vessel dilation in response to whisker stimulation in each barrel. They found that the response of blood vessels to was very heterogeneous: some vessels in barrel W1 dilated when whisker W1 was stimulated, some did not, and some actually dilated when whisker W2 was stimulated. Further experiments showed that blood vessels were not dilating due to increased neuronal activity in their immediate surroundings. Instead, downstream neuronal activity sent a signal up the vessel, causing dilation; meaning that blood vessels dilated in response to downstream neuronal activity. So, in the example above, a blood vessel that was imaged in barrel W1, but was in fact carrying blood toward W2, would dilate in response to neuronal activity in W2 and not W1.
What's the impact?
This study shed light on the spatial regulation of neurovascular coupling. As the spatial resolution of imaging techniques such as fMRI increase, these findings are incredibly relevant: they suggest that at high resolutions, changes in blood vessels do not report neuronal activity of their surroundings, but instead reflect an integration of neuronal activity downstream.