Complementary stable and dynamic prelimbic ensembles encode learned threat value underlying generalization and...

Area of Science:

• Neuroscience
• Behavioral Neuroscience
• Systems Neuroscience

Background:

• Adaptive behavior relies on assigning emotional value to sensory cues and generalizing to similar stimuli.
• The prelimbic cortex (PL) is crucial for threat expression and discrimination, but its neuronal ensembles change over time.
• Understanding how stable population codes form amidst neuronal reorganization is a key challenge.

Purpose of the Study:

• To investigate how the prelimbic cortex (PL) maintains stable population codes for threat value during fear learning and generalization.
• To determine if PL activity primarily encodes stimulus significance or behavioral responses like freezing.
• To elucidate the roles of stable and dynamic neuronal populations in threat-value representation and generalization.

Main Methods:

• Longitudinal in vivo calcium imaging was performed in freely moving mice over 30 days.
• Mice underwent auditory discriminative fear learning and retrieval tasks.
• Generalized linear models were used to analyze the relationship between PL activity, learned threat value, and freezing behavior.

Main Results:

• Stable graded representations persisted in PL neuronal populations despite substantial ensemble turnover.
• Learned threat value, not freezing behavior, better explained PL activity, indicating a primary role in encoding stimulus significance.
• Higher population similarity was observed for shock-associated and generalized tones, suggesting a stable code for threat generalization.
• Specific neuronal populations (stable graded vs. dynamic frequency-selective) differentially contributed to threat-value coding and learning.

Conclusions:

• The prelimbic cortex (PL) establishes stable representations of learned threat value essential for generalization, even with ongoing neuronal reorganization.
• Both stable and dynamic neuronal populations within the PL contribute to adaptive threat-value coding.
• These findings provide insights into the neural mechanisms of threat generalization and adaptive behavior.