Acetylcholine modulates prefrontal outcome coding during threat learning under uncertainty.

Area of Science:

• Neuroscience
• Computational Neuroscience
• Decision Making

Background:

• Learning rate adaptation is crucial for decision-making under outcome variability.
• The medial prefrontal cortex (mPFC) encodes expected outcomes and prediction errors, vital for learning rate control.
• The neural sources influencing mPFC coding properties for prediction errors remain largely unknown.

Purpose of the Study:

• To investigate the role of basal forebrain cholinergic projections in shaping mPFC responses to surprising outcomes.
• To understand how acetylcholine influences the encoding of prediction errors in the mPFC.
• To determine the impact of cholinergic modulation on decision-making based on outcome variability.

Main Methods:

• Utilized one-photon calcium imaging in mice to record mPFC neuronal activity during a threat-learning task.
• Employed optogenetic stimulation of basal forebrain cholinergic terminals to manipulate cholinergic signaling.
• Analyzed neuronal responses to threat occurrence, omission, and their unexpectedness.

Main Results:

• Identified mPFC cells responding to threats and threat omissions, with responses scaled to outcome unexpectedness.
• Observed selectivity for signed prediction errors, including reversals based on surprising threats versus omissions.
• Demonstrated that optogenetic cholinergic stimulation enhanced threat-evoked signals and led to maladaptive decision-making, abandoning choices after unexpected threats.

Conclusions:

• Cholinergic input from the basal forebrain modulates mPFC encoding of surprising outcomes (prediction errors).
• Acetylcholine signaling influences the impact of unexpected events on future choices, potentially decoupling behavior from learned contingencies.
• This study elucidates a key mechanism by which acetylcholine regulates learning and decision-making under uncertainty.