A study published on Jul. 9 by scientists at St. Jude Children's Research Hospital found that overactive epinephrine-producing C1 neurons in mice are associated with prolonged anxiety responses. The research, published in Neuron, showed that while these neurons typically have temporarily elevated activity during stress, persistent activation led to heightened anxiety lasting for several days.
The researchers reported that inhibiting C1 neurons reduced anxiety-like behaviors in mice, suggesting a potential therapeutic target for anxiety disorders. Lindsay Schwarz, PhD, Department of Developmental Neurobiology at St. Jude Children's Research Hospital, said, "Considering the basic functions that the RVLM controls, it was assumed that neurons controlling complex behaviors such as fear and anxiety wouldn't be found there. Despite being within the RVLM, C1 neurons appear to be doing something different from the neurons around them, suggesting an unappreciated capacity of what these brain regions can do."
C1 neurons are located in the rostral ventrolateral medulla (RVLM), a region involved in controlling breathing and cardiac function. Using a precision-targeting system developed by Schwarz's lab, researchers were able to selectively study these subpopulations and determined that activating C1 neurons excites cells within the periaqueductal grey matter (PAG), which regulates physiological and behavioral responses to stress.
Schwarz said, "Signaling from these neurons to the PAG is very powerful in producing long-lasting anxiety. C1 neuron activation increases PAG activity in stressful situations, but normally, we think this circuit turns off when the stress has passed. We found that strong activation may keep it on too long, leading to prolonged anxiety." The team also discovered that blocking C1 neuron activation was most effective at reducing anxiety after highly stressful events.
"When we blocked these neurons during a period of heightened stress, the mice were less affected by subsequent stressful events. This suggests C1 neurons play a key role in regulating anxiety over time," Schwarz said. "Importantly, blocking these neurons doesn't affect behavior in the moment. So targeting them therapeutically may be an effective strategy without causing issues otherwise." The study's first author is Carlos Fernández-Peña; other authors include Rachel Pace, Lourds Fernando, Heather Sheppard and Brittany Pittman.
