Functional diversity of dopamine axons in prefrontal cortex during classical conditioning

Area of Science:

• Neuroscience
• Neurobiology

Background:

• Midbrain dopamine neurons project to the prefrontal cortex (PFC), influencing neural processing.
• The specific signals transmitted by these mesocortical projections, especially at the single-axon level, are not well understood.

Purpose of the Study:

• To investigate the activity of dopaminergic axons in the medial prefrontal cortex (mPFC) during processing of reward and aversive stimuli.
• To understand how dopamine axon activity changes with learning and cue discrimination.

Main Methods:

• Utilized optimized microprism-mediated two-photon calcium imaging to observe dopamine axon terminals in the mPFC.
• Employed machine learning to infer trial-by-trial cue discrimination based on behavioral responses like licking and facial expressions.

Main Results:

• Observed diverse dopamine axonal activity, with some axons preferring reward and others aversive stimuli; a population-level bias towards aversive stimuli was noted.
• Found that reward/aversive stimulus preference in axons persisted through classical conditioning.
• Demonstrated that aversive-preferring axons developed cue activity preference as mice learned to discriminate cues, with successful discrimination correlating with sharper aversive cue selectivity.

Conclusions:

• A subset of mesocortical dopamine axons encodes aversive-related signals.
• This aversive signaling is dynamically modulated by both long-term classical conditioning and short-term trial-by-trial cue discrimination.