When stressful events pass, most of us expect our anxiety to fade. But scientists at St. Jude Children’s Research Hospital in Memphis have discovered why sometimes it doesn’t — and the answer lies in a small cluster of brain cells called C1 neurons.
The researchers found that these neurons, located in a region of the brainstem called the rostral ventrolateral medulla, act like an internal alarm system. When activated by stress, they send signals to another brain region called the periaqueductal gray, or PAG, which helps control how our bodies respond to danger. For most people, this circuit shuts off once the threat is gone. But when C1 neurons stay highly active, anxiety can persist for up to a week.
The study, published in the journal Neuron, was led by Lindsay Schwarz, a researcher in the Department of Developmental Neurobiology at St. Jude. Her team used a precision-targeting system designed in her lab to isolate C1 neurons from other similar cells nearby — something scientists had struggled to do before.
"We found that strong activation may keep this circuit on too long, leading to prolonged anxiety," Schwarz said.
The findings are especially significant because anxiety disorders affect more than 300 million people worldwide. Existing medications can help, but they often affect signaling across the entire brain and body, which can lead to unwanted side effects that discourage long-term use. What makes C1 neurons stand out is that they appear to promote anxiety without directly interfering with other autonomic functions like breathing or heart rate.
"C1 neurons appear to promote anxiety without directly affecting autonomic functions," Schwarz said. "This suggests they may be a better target than broadly affecting signaling across the entire brain and body."
When the researchers blocked C1 neurons in mice during periods of heightened stress, the animals showed less anxiety in response to later stressful events. Interestingly, blocking these neurons did not change the mice's immediate behavior — only their future anxiety levels.
"Targeting them therapeutically may be an effective strategy without causing issues otherwise," Schwarz said.
The discovery challenges a long-held assumption that brain regions controlling basic life functions like breathing and heart rate would not also be involved in complex emotional responses like fear and anxiety. Despite being nestled in the RVLM alongside neurons that regulate heartbeat and circulation, C1 neurons seem to be doing something quite different from their neighbors.
While the research was conducted in mice, the findings open a new avenue for understanding and potentially treating anxiety disorders in humans. Schwarz and her team are hopeful that C1 neurons could one day become the focus of targeted therapies that ease anxiety without the broad side effects of current medications.