Functional Diversity of Dopamine Axons in Prefrontal Cortex During Classical Conditioning

Area of Science:

• Neuroscience
• Cellular Neuroscience

Background:

• Midbrain dopamine neurons project to the prefrontal cortex (PFC), influencing neural processing.
• The specific signals conveyed by these mesocortical projections at the single-axon level remain largely unknown.

Approach:

• Utilized microprism-mediated two-photon calcium imaging to monitor dopamine axon terminal activity in the medial PFC (mPFC) of mice.
• Investigated axonal responses during reward and aversive processing, including classical conditioning and cue discrimination tasks.
• Employed machine learning to infer trial-by-trial cue discrimination from behavioral data (licking, facial expressions).

Key Points:

• Dopamine axons in the mPFC exhibit varied responses, with a population-level bias towards aversive stimuli.
• Axonal preference for reward or aversive stimuli was maintained during classical conditioning.
• Aversive-preferring axons developed cue activity preference as mice learned to discriminate cues, enhancing selectivity for aversive cues during successful discrimination.

Conclusions:

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