Change in astrocyte activity also influenced neural circuits.
Image Credit: Scientific Frontline
Scientific Frontline: "At a Glance" Summary: The Role of Astrocytes in Aversive Memory
- Main Discovery: Astrocytes, previously considered mere support and housekeeping cells in the brain, actively encode, maintain, and regulate neural fear signaling within the amygdala, challenging the traditional neuron-centric model of fear memory.
- Methodology: Researchers utilized a mouse model in conjunction with fluorescent activity sensors to monitor astrocyte responses in real time during the formation, retrieval, and extinction of fear memories, while selectively increasing or suppressing astrocyte signals to neighboring neurons to observe behavioral changes.
- Key Data: Altering astrocyte signaling caused a direct and parallel shift in the strength of fear memories, with the observed diminishment of astrocyte activity actively correlating with the successful extinction of those fear memories.
- Significance: This study demonstrates that astrocytes are active participants in shaping fear responses and influencing broader neural circuits, including the critical transmission of fear signals to the prefrontal cortex to govern defensive decision-making.
- Future Application: Targeting astrocyte-related pathways provides a novel therapeutic avenue that could complement neuron-focused treatments for conditions driven by persistent aversive memories, such as post-traumatic stress disorder, anxiety disorders, and phobias.
- Branch of Science: Neuroscience, Behavioral Neuroscience, and Neurobiology.
- Additional Detail: When astrocyte activity was artificially disrupted, surrounding neurons were completely unable to form normal fear-related activity patterns, confirming that fear memories and corresponding defensive reactions cannot be generated or managed by neurons alone.
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.
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| Lindsay Halladay Photo Credit: Courtesy of University of Arizona |
"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.
Published in journal: Nature
Title: Astrocytes enable amygdala neural representations supporting memory
Authors: 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, and Andrew Holmes
Source/Credit: University of Arizona | Niranjana Rajalakshmi
Reference Number: ns022126_02
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