Translating Thought into Blood Flow in the Brain: Capillaries as Sensors of Neural Activity

NIH Director's Wednesday Afternoon Lecture Series The Nelson laboratory ’ s research interests include elucidating the mechanisms by which cerebral blood flow is controlled to meet the diverse and ever-changing demands of active neurons and how these mechanisms are disrupted in small vessel disease (SVD) — a major cause of stroke and dementia. Dr. Nelson and colleagues have unraveled many of the major mechanisms that control cerebrovascular function, including the discovery of local calcium signals ( “ sparks ” ), which counter-intuitively oppose vasoconstriction. They have recently shown that brain capillaries act as a neural activity-sensing network by initiating and transmitting an electrical signal, mediated by potassium channel activation, that propagates through the interconnected endothelial cells comprising the capillaries that line all blood vessels. This concept explains the rapid and coordinated delivery of blood to active neurons. Using a mouse model of a monogenic form of SVD, they have discovered early defects that result in a loss of this electrical signaling mechanism and impaired delivery of blood to active neurons — defects that involve changes in extracellular matrix composition. The near-term goals of Nelson laboratory researchers are to create an integrated view of electrical, calcium and related regulatory signaling mechanisms at molecular, biophysical, and computational-modeling levels by examining their operation in increasingly complex segm...
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