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Midbrain PAG Astrocytes Modulate Mouse Defensive and Panic-Like Behaviors
Ellane Barcelon1,2, Kyungchul Noh1,3, Minkyu Hwang4
1Department of Physiology and Neuroscience, Dental Research Institute, Seoul National University, School of Dentistry, Seoul, Republic of Korea.
Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|February 4, 2026
Summary
Astrocytes in the midbrain periaqueductal gray (PAG) activate during threats, triggering defensive behaviors. Aberrant astrocyte activation causes panic-like responses, revealing their role in defensive behavior regulation.
Area of Science:
- Neuroscience
- Cell Biology
Background:
- Defensive behaviors are vital for survival.
- Maladaptive neural functions in defensive behavior can lead to panic-like states.
- The midbrain periaqueductal gray (PAG) is known to control defensive behaviors, but the specific substrates of dysregulated panic-like responses are unclear.
Purpose of the Study:
- To investigate the role of astrocytes in the PAG in controlling defensive behaviors.
- To identify the neurobiological substrates underlying dysregulated panic-like defensive responses.
Main Methods:
- In vivo calcium imaging and recordings in mice.
- Optogenetic modulation of PAG astrocytes.
- Electrophysiological experiments.
Main Results:
- PAG astrocytes are activated during threatening situations and initiate defensive behaviors.
- PAG astrocyte activation and subsequent ATP release are essential for optimal defensive behavior.
- Aberrant activation of PAG astrocytes results in maladaptive defensive behavior, mimicking panic-like behavior.
Conclusions:
- PAG astrocytes are key neurobiological substrates involved in defensive behavior regulation.
- Increased calcium activity and ATP release by PAG astrocytes may be crucial in panic-related behaviors.
- Targeting PAG astrocyte function could offer new avenues for addressing panic disorders.
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