Differential modulation of aversive signaling by expectation across the cingulate cortex

Area of Science:

• Neuroscience
• Cognitive Neuroscience
• Computational Neuroscience

Background:

• Pain-related aversion is crucial for learning and survival, engaging widespread cortical networks.
• The specific roles of distinct cingulate subregions in pain aversion's adaptive utility are poorly understood.

Purpose of the Study:

• To investigate the distinct contributions of the anterior cingulate cortex (ACC) and retrosplenial cortex (RSC) to pain-related aversion.
• To compare neural dynamics in ACC and RSC during nociception, fear conditioning, and extinction.

Main Methods:

• Longitudinal one-photon calcium imaging in mice.
• Utilized repeated unsignaled foot-shocks and a fear conditioning and extinction paradigm.
• Compared population activity dynamics in ACC and RSC.

Main Results:

• Both ACC and RSC showed stable ensembles responding to acute shocks, indicating shared nociceptive encoding.
• RSC population activity flexibly reorganized when shocks were predicted by cues, unlike the ACC.
• RSC anticipatory dynamics predicted individual differences in fear learning and extinction rates.
• ACC dynamics primarily encoded immediate freezing decisions, reflecting ongoing nociception.

Conclusions:

• A division of labor exists: ACC focuses on ongoing nociception and immediate defense, while RSC transforms sensory input into predictive codes for learning and memory.
• Specialized cortical computations in ACC and RSC cooperate to generate the adaptive value of pain aversion.
• These regions play complementary roles in immediate responses and long-term behavioral adaptation to aversive stimuli.