Abstract

A key characteristic of many anxiety disorders is the generalization of fear to neutral stimuli. After contextual fear conditioning mice display higher levels of freezing in the training context compared to a novel context when tested within 24 hours. Over time, mice freeze in novel contexts to the same degree as they do in the training context, displaying generalization of the fear response. Our research shows that inactivating the ventral hippocampus (vHPC) or the anterior cingulate cortex (ACC) during a remote test restores memory precision, such that mice display reduced freezing in the novel context. We further investigated these brain regions’ involvement in generalization by disrupting their projections to the basolateral amygdala (BLA), which is a critical area for expression of fear memories. Using chemogenetics, we disrupted projections from either the vHPC or ACC to the BLA. When projections from the vHPC to BLA are silenced, mice show a reduction in freezing in the novel context compared to mice with intact projections at a remote time point. Additionally, inhibiting projections from the ACC to the BLA during a remote test, mice displayed a drastic reduction in freezing to the novel context compared to controls which displayed high levels of freezing in both the training and novel contexts. These results identify a novel neural circuit through which fear generalization occurs and are helpful in understanding the neural processes involved in generalized anxiety disorders.

Modified Abstract

A characteristic of anxiety disorders is the generalization of fear to neutral stimuli. Immediately after context fear conditioning mice display higher levels of freezing in the training context compared to a novel context; over time, mice generalize their fear to novel contexts. Using chemogenetics, we investigated the fear generalization circuit by disrupting projections from either the ventral hippocampus (vHPC) or the anterior cingulate cortex (ACC) to the basolateral amygdala (BLA). Inhibiting projections from the vHPC to the BLA reduced freezing in the novel context; whereas inhibiting projections from the ACC to the BLA completely eliminated freezing in the novel context. These results suggest a fear generalization circuit and are helpful in understanding the neural processes involved in generalized anxiety disorders.

Research Category

Psychology

Primary Author's Major

Psychology

Mentor #1 Information

Aaron Jasnow

Presentation Format

Poster

Start Date

21-3-2017 1:00 PM

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Research Area

Animal Experimentation and Research | Behavioral Neurobiology | Neurosciences

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Mar 21st, 1:00 PM

A Neural Circuit Controlling Fear Generalization

A key characteristic of many anxiety disorders is the generalization of fear to neutral stimuli. After contextual fear conditioning mice display higher levels of freezing in the training context compared to a novel context when tested within 24 hours. Over time, mice freeze in novel contexts to the same degree as they do in the training context, displaying generalization of the fear response. Our research shows that inactivating the ventral hippocampus (vHPC) or the anterior cingulate cortex (ACC) during a remote test restores memory precision, such that mice display reduced freezing in the novel context. We further investigated these brain regions’ involvement in generalization by disrupting their projections to the basolateral amygdala (BLA), which is a critical area for expression of fear memories. Using chemogenetics, we disrupted projections from either the vHPC or ACC to the BLA. When projections from the vHPC to BLA are silenced, mice show a reduction in freezing in the novel context compared to mice with intact projections at a remote time point. Additionally, inhibiting projections from the ACC to the BLA during a remote test, mice displayed a drastic reduction in freezing to the novel context compared to controls which displayed high levels of freezing in both the training and novel contexts. These results identify a novel neural circuit through which fear generalization occurs and are helpful in understanding the neural processes involved in generalized anxiety disorders.