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Rare Stress-Sensitive Neurons May Regulate Blood Flow and Brain Activity Across the Whole Brain

Scientists at Pennsylvania State University found that a sparse population of type-I nNOS neurons helps regulate cerebral blood flow, vasomotion, and large-scale neural activity in mice. Removing these stress-sensitive cells reduced blood flow, weakened delta sleep waves, and lowered synchrony between hemispheres, with stronger effects during sleep. The results suggest these neurons could support waste clearance and healthy sleep, and their loss may contribute to neurodegenerative risk — but human studies are needed to confirm relevance.

Rare Stress-Sensitive Neurons May Regulate Blood Flow and Brain Activity Across the Whole Brain

Small population of type-I nNOS neurons influences global brain blood flow and activity

Researchers at Pennsylvania State University report that a tiny, stress-sensitive group of neurons — type-I nNOS cells — appears to exert outsized control over cerebral blood flow, vascular pulsations (vasomotion), and widespread neural activity in mice. The team selectively removed these neurons to study their role and observed measurable changes in brain physiology.

Key findings

Reduced blood flow and vasomotion: Ablation of type-I nNOS neurons led to lower overall cerebral blood flow and a marked reduction in the amplitude of spontaneous vascular oscillations that help move fluid through brain tissue.

Weaker neural signals and sleep-related waves: Neural activity declined and the slow, high-amplitude delta waves associated with deep sleep became weaker. The changes in blood flow and neural firing were more pronounced during sleep periods.

Decreased hemispheric synchrony: The left and right hemispheres of the mice showed reduced synchrony after the neurons were removed, suggesting a role for these cells in coordinating brain-wide activity.

"In your brain, arteries, veins, and capillaries help move fluid around by constantly dilating and constricting every few seconds, which we call spontaneous oscillation," says biomedical engineer Patrick Drew. "Earlier work from our lab indicated nNOS neurons are important for controlling cerebral blood flow. After targeting and removing a subset of those neurons, we recorded a marked reduction in the amplitude of these oscillations."

Implications and limitations

The findings suggest type-I nNOS neurons may support processes that depend on robust blood flow and vascular pulsation — including the clearance of metabolic waste from brain tissue (a mechanism linked to neurodegenerative disease risk) and the generation of sleep-associated delta waves. Because these neurons appear vulnerable to psychological stress, their loss could represent an environmental contributor to poor brain health and sleep disruption.

However, these experiments were performed in mice. The authors caution that follow-up studies are needed to determine whether the same mechanisms operate in humans and to explore whether protecting or restoring these rare neurons could be a therapeutic strategy.

Publication: The study was published in eLife.