Summary: For decades, astrocytes—star-shaped cells in the brain—were dismissed as mere “housekeepers” that glued neurons together. However, a new study has revealed that these cells are actually master regulators of fear.
The research shows that astrocytes in the amygdala are essential for learning what to fear, recalling those memories, and—most importantly—learning when to let them go. By actively shaping neural activity rather than just supporting it, astrocytes have become a primary target for understanding and treating disorders like PTSD and chronic anxiety.
Key Facts
- Active Participants: Astrocytes encode and maintain neural fear signaling in the amygdala, proving they are as vital to memory as neurons.
- Extinguishing Fear: The study found that astrocyte activity diminishes as fear memories are extinguished. Selectively manipulating these cells can strengthen or weaken a fear memory.
- Circuit Breakdown: When astrocyte activity is disrupted, neurons can no longer form the patterns needed to transmit defensive reactions to the rest of the brain.
- Prefrontal Connection: Disruption in the amygdala’s astrocytes ripples to the prefrontal cortex, affecting how the brain makes decisions in fearful situations.
- Therapeutic Potential: Targeting astrocyte-specific pathways offers a new frontier for treating PTSD, phobias, and anxiety disorders, complementing traditional neuron-focused therapies.
Source: University of Arizona
Picture a star-shaped cell in the brain, stretching its spindly arms out to cradle the neurons around it. That’s an astrocyte, and for a long time, scientists thought its job was caretaking the brain, gluing together neurons, and maintaining neural circuits.
But now, a new study reveals that these supposed support cells that are spread all over the brain are as important as neurons in fear memory.
“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 lab collaborated with researchers from the National Institutes of Health for this multi-institutional study, led by Andrew Holmes and Olena Bukalo of the Laboratory of Behavioral and Genomic Neuroscience.
The study, published in Nature, suggests that astrocytes present in the brain’s fear center, the amygdala, help the brain learn what to fear, recall those memories, and crucially, learn when to let them go.
The findings challenge long-held assumptions about how fear memory works, pointing toward new treatment approaches for disorders such as post-traumatic stress disorder.
“For the first time, we found that astrocytes encode and maintain neural fear signaling,” Halladay said.
The team used a mouse model to understand how fear learning as a mechanism takes place in the brain, how fear-related memories can be retrieved, and the contribution of neurons versus astrocytes to fear learning.
Using fluorescent activity sensors, the team watched astrocytes respond in real time as fear memories were formed and later retrieved. As those memories were extinguished, astrocyte activity diminished.
When the researchers then selectively increased or suppressed the signals astrocytes send to neighboring neurons, the strength of fear memories shifted in parallel, demonstrating that astrocytes are not just passive bystanders, but active participants in shaping fear.
Change in astrocyte activity also influenced neural circuits. When the astrocyte activity was disrupted, neurons could no longer form normal fear-related activity patterns and effectively transmit information about appropriate defensive reactions to brain regions that help control defensive behavior. These findings challenge neuron-centric models of fear by showing that fear memories aren’t produced by neurons alone.
The impact of disrupting astrocytes rippled beyond the amygdala. The manipulations also influenced how fear signals were relayed to the prefrontal cortex, a brain region that is key for decision-making.
This suggests that astrocytes not only influence encoding of fear memories by the amygdala, but also how the brain uses those memories to determine appropriate responses to fearful situations.
Knowing that astrocytes play a key role in the retrieval of fear memories will reshape therapeutic interventions for disorders driven by persistent fearful memories such as post-traumatic stress disorder, anxiety disorders and phobias, Halladay said.
If astrocytes help determine whether fear memories are expressed or successfully extinguished, then targeting astrocyte-related pathways, rather than neural pathways, could eventually complement neuron-focused therapies.
Halladay’s next goal is to study what astrocytes are doing across the rest of brain’s fear circuitry, as the amygdala doesn’t act alone and relies on other regions of the brain. For example, the prefrontal cortex helps with decision making during fearful situations, while deeper structures like the periaqueductal gray in the midbrain execute specific defensive behaviors such as freezing and fleeing.
While it is not certain what functions astrocytes have in those regions, Halladay said there is a significant chance that astrocytes are contributing to neural function 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.
Key Questions Answered:
A: That’s the old model. We now know astrocytes are interwoven with neurons and act more like a “co-processor.” They don’t just hold neurons in place; they actively decide which fear signals get passed along and which ones get muted.
A: They might be the key. PTSD is essentially a fear memory that won’t “extinguish.” Since this study shows astrocytes are responsible for the process of letting go of fear, future drugs could target these cells to help the brain finally delete traumatic associations.
A: Because of their shape! Under a microscope, they look like tiny stars (from the Greek astron) with long, spindly arms that cradle and communicate with thousands of nearby neurons.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our staff.
About this PTSD and neuroscience research news
Author: Niranjana Sahasranamam Rajalakshmi
Source: University of Arizona
Contact: Niranjana Sahasranamam Rajalakshmi – University of Arizona
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Astrocytes enable amygdala neural representations supporting memory” by Olena Bukalo, Ruairi O’Sullivan, Yuta Tanisumi, Adriana Mendez, Chase Weinholtz, Sydney Zimmerman, Victoria Offenberg, Olivia Carpenter, Hrishikesh Bhagwat, Sophie Mosley, John J. O’Malley, Kerri Lyons, Yulan Fang, Jess Goldschlager, Linnaea E. Ostroff, Mario A. Penzo, Hiroaki Wake, Lindsay R. Halladay & Andrew Holmes. Nature
DOI:10.1038/s41586-025-10068-0
Abstract
Astrocytes enable amygdala neural representations supporting memory
Brain systems mediating responses to previously encountered threats provide critical survival functions. Fear memory and extinction are underpinned by neural representations in the basolateral amygdala (BLA), but the contribution of non-neuronal cells, including astrocytes, to these processes remains unresolved.
Here, using in vivo calcium (Ca2+) imaging and causal astrocyte manipulations, we find that BLA astrocytes dynamically track fear state and support fear memory retrieval and extinction.
By combining astrocyte manipulations with in vivo BLA neuronal Ca2+ imaging and electrophysiological recordings, we show that astrocyte Ca2+ signalling enables neuronal encoding of fear memory retrieval and extinction, and readout through a BLA–prefrontal circuit.
Our findings reveal a key role for astrocytes in the generation and adaptation of fear-state-related neural representations, revising neurocentric models of critical amygdala-mediated adaptive functions.
