eLife (May 2024)

Functional diversity of dopamine axons in prefrontal cortex during classical conditioning

  • Kenta Abe,
  • Yuki Kambe,
  • Kei Majima,
  • Zijing Hu,
  • Makoto Ohtake,
  • Ali Momennezhad,
  • Hideki Izumi,
  • Takuma Tanaka,
  • Ashley Matunis,
  • Emma Stacy,
  • Takahide Itokazu,
  • Takashi R Sato,
  • Tatsuo Sato

DOI
https://doi.org/10.7554/eLife.91136
Journal volume & issue
Vol. 12

Abstract

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Midbrain dopamine neurons impact neural processing in the prefrontal cortex (PFC) through mesocortical projections. However, the signals conveyed by dopamine projections to the PFC remain unclear, particularly at the single-axon level. Here, we investigated dopaminergic axonal activity in the medial PFC (mPFC) during reward and aversive processing. By optimizing microprism-mediated two-photon calcium imaging of dopamine axon terminals, we found diverse activity in dopamine axons responsive to both reward and aversive stimuli. Some axons exhibited a preference for reward, while others favored aversive stimuli, and there was a strong bias for the latter at the population level. Long-term longitudinal imaging revealed that the preference was maintained in reward- and aversive-preferring axons throughout classical conditioning in which rewarding and aversive stimuli were paired with preceding auditory cues. However, as mice learned to discriminate reward or aversive cues, a cue activity preference gradually developed only in aversive-preferring axons. We inferred the trial-by-trial cue discrimination based on machine learning using anticipatory licking or facial expressions, and found that successful discrimination was accompanied by sharper selectivity for the aversive cue in aversive-preferring axons. Our findings indicate that a group of mesocortical dopamine axons encodes aversive-related signals, which are modulated by both classical conditioning across days and trial-by-trial discrimination within a day.

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