These overlooked brain cells may control fear and PTSD

New research is now challenging that idea. These widely distributed "support cells" appear to be just as important as neurons when it comes to forming and controlling fear memories.

"Astrocytes are interwoven among neurons in the brain, and it seemed unlikely they were there just for housekeeping. We wanted to understand what they're actually doing -- and how they're shaping neural activity in the process," said Lindsay Halladay, assistant professor at the University of Arizona Department of Neuroscience and one of the study's senior authors.

Halladay's team worked with scientists from the National Institutes of Health on this multi-institutional project, led by Andrew Holmes and Olena Bukalo of the Laboratory of Behavioral and Genomic Neuroscience.

Astrocytes Help the Brain Learn and Let Go of Fear

The study, published in Nature, focused on the amygdala, a key region involved in processing fear. Researchers found that astrocytes in this area play a direct role in how the brain learns what to fear, retrieves those memories, and importantly, learns when those fears are no longer relevant.

"For the first time, we found that astrocytes encode and maintain neural fear signaling," Halladay said.

This discovery challenges long-standing views that placed neurons at the center of fear processing and suggests new ways to approach conditions like post-traumatic stress disorder.

Watching Fear Form in Real Time

To explore how fear memories develop, the team used a mouse model and closely tracked brain activity. With the help of fluorescent sensors, they were able to observe astrocytes as fear memories were created and later recalled.

Astrocyte activity increased during both learning and recall. When fear memories were gradually extinguished, activity in these cells declined. The researchers then altered the signals astrocytes send to nearby neurons. Strengthening those signals made fear memories more intense, while weakening them reduced the response.

These results show that astrocytes are not passive helpers. They actively shape how fear is stored and expressed in the brain.

Disrupting Astrocytes Alters Brain Circuits

Changing astrocyte activity also affected how neurons behaved. When astrocyte signaling was disrupted, neurons struggled to form the normal activity patterns linked to fear. This impaired their ability to send information about appropriate defensive responses to other parts of the brain.

The findings challenge the traditional neuron-focused view of fear, showing that neurons do not act alone in generating fear memories.

Beyond the Amygdala: A Broader Fear Network

The effects of astrocytes extended beyond the amygdala. Changes in their activity also influenced how fear-related signals reached the prefrontal cortex, a region involved in decision-making.

This suggests astrocytes help not only create fear memories but also guide how the brain uses those memories to choose appropriate reactions in threatening situations.

New Possibilities for Treating PTSD and Anxiety

Understanding the role of astrocytes could reshape how scientists approach disorders linked to persistent fear, including post-traumatic stress disorder, anxiety disorders and phobias.

If astrocytes help control whether fear memories are expressed or fade away, future treatments might target these cells alongside neurons to improve outcomes.

Expanding Research Across the Brain's Fear Circuitry

Halladay's next step is to investigate astrocytes throughout the broader network involved in fear. The amygdala works alongside other brain regions. The prefrontal cortex helps guide decisions in fearful situations, while deeper areas such as the periaqueductal gray in the midbrain control responses like freezing or fleeing.

Although the exact role of astrocytes in these regions is still unclear, researchers believe they are likely contributing there as well.

"Understanding that larger circuit could help answer a simple question of why someone with an anxiety disorder might exhibit inappropriate fear responses to something that isn't actually dangerous," Halladay said.