Divergent encoding of active avoidance behavior in corticostriatal and corticolimbic projections

Area of Science:

• Neuroscience
• Behavioral Neuroscience
• Anxiety Disorders Research

Background:

• Active avoidance behavior is essential for survival and offers insights into anxiety disorders.
• The dorsomedial prefrontal cortex (dmPFC) is implicated in regulating active avoidance through projections to the striatum and amygdala.
• The endogenous activity of dmPFC projections during active avoidance learning has not been previously recorded.

Purpose of the Study:

• To record and analyze the endogenous activity of the dmPFC and its projections to the dorsomedial striatum (DMS) and basolateral amygdala (BLA) during active avoidance learning.
• To investigate how neural activity in these pathways relates to conditioned stimulus (CS) presentation and specific avoidance behaviors.
• To elucidate the distinct roles of dmPFC-DMS and dmPFC-BLA projections in active avoidance learning.

Main Methods:

• Utilized fiber photometry to record neural activity in the dmPFC and its axonal projections to the DMS and BLA in male and female mice.
• Monitored neural activity during active avoidance learning tasks, including conditioned stimulus (CS) presentations and behavioral responses (active avoidance, cued freezing).
• Analyzed learning-related changes in neural activity patterns associated with specific behaviors.

Main Results:

• Both dmPFC-DMS and dmPFC-BLA projections exhibited learning-related increases in activity during CS onset throughout active avoidance training.
• The dmPFC showed increased activity during active avoidance and decreased activity during cued freezing.
• dmPFC-DMS and dmPFC-BLA projections demonstrated divergent encoding of active avoidance, with increased activity in dmPFC-DMS and decreased activity in dmPFC-BLA during active avoidance.

Conclusions:

• Projection-specific subpopulations within the dmPFC encode task-relevant information during active avoidance learning.
• The dmPFC-DMS and dmPFC-BLA pathways play distinct yet complementary roles in the learning and execution of active avoidance behaviors.
• These findings provide novel insights into the neural circuitry underlying active avoidance and its potential dysregulation in anxiety disorders.