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Updated: Jan 19, 2026

A Novel Pavlovian Fear Conditioning Paradigm to Study Freezing and Flight Behavior
Published on: January 5, 2021
The amygdala differentially regulates defensive behaviors evoked by CO2
R J Taugher1, B J Dlouhy2, C J Kreple3
1Department of Psychiatry, University of Iowa, Iowa City, IA, USA; Department of Veterans Affairs Medical Center, Iowa City, IA, USA.
Abstract:
CO2 inhalation can provoke panic attacks in humans, and the likelihood is increased in patients with panic disorder. Identifying brain sites involved could provide important mechanistic insight into the illness. In mice, the amygdala has been suggested to promote CO2 responses; however, recent studies in humans with amygdala damage indicate the amygdala is not required for CO2-induced fear and panic and might actually oppose these responses. To clarify the role of the amygdala, we produced lesions in mice paralleling the human lesions, and characterized behavioral responses to CO2. Compared to sham controls, we found that amygdala-lesioned mice froze less to 10% CO2, and unlike shams they also began to jump frenetically. At 20% CO2, controls also exhibited jumping, suggesting it is a normal response to more extreme CO2 concentrations. The effect of amygdala lesions was specific to CO2 as amygdala-lesioned mice did not jump in response to a predator odor or to an auditory conditioned stimulus. In amygdala-lesioned mice, jumping evoked by 10% CO2 was eliminated by co-lesioning the dorsal periaqueductal gray, a structure implicated in panic and escape-related behaviors. Together, these observations suggest a dual role for the amygdala in the CO2 response: promoting CO2-induced freezing, and opposing CO2-induced jumping, which may help explain the exaggerated CO2 responses in humans with amygdala lesions.
Insights
Carbon dioxide (CO2) inhalation triggers panic. Amygdala lesions in mice reduced freezing but increased jumping to CO2, suggesting the amygdala opposes panic-like jumping.
Area of Science:
- Neuroscience
- Behavioral Neuroscience
- Panic Disorder Research
Background:
- Carbon dioxide (CO2) inhalation is a known panicogen in humans, particularly in those with panic disorder.
- The amygdala's role in CO2-induced fear and panic is debated, with human studies suggesting it may oppose these responses, contrary to rodent models.
Purpose of the Study:
- To investigate the role of the amygdala in CO2-induced behavioral responses in mice.
- To clarify the amygdala's function in panic-related behaviors by creating lesions analogous to those in human studies.
Main Methods:
- Mice underwent amygdala lesions or sham procedures.
- Behavioral responses (freezing, jumping) to varying CO2 concentrations (10% and 20%) were assessed.
- Responses to predator odor and auditory stimuli were also evaluated.
- The effect of co-lesioning the dorsal periaqueductal gray was examined.
Main Results:
- Amygdala-lesioned mice showed reduced freezing but increased jumping behavior in response to 10% CO2 compared to controls.
- Jumping, observed in controls at 20% CO2, suggests it's a concentration-dependent response.
- Amygdala lesions specifically affected CO2 responses, not reactions to predator odor or auditory stimuli.
- Co-lesioning the dorsal periaqueductal gray abolished CO2-induced jumping in amygdala-lesioned mice.
Conclusions:
- The amygdala appears to have a dual role: promoting CO2-induced freezing and inhibiting CO2-induced jumping.
- These findings may help explain exaggerated CO2 responses in humans with amygdala damage or lesions.
- The dorsal periaqueductal gray is critical for mediating CO2-induced jumping, especially when the amygdala's inhibitory influence is removed.
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