The Raphe Dopamine System Controls the Expression of Incentive Memory

Neuron. 2020 May 6;106(3):498-514.e8. doi: 10.1016/j.neuron.2020.02.009. Epub 2020 Mar 6.


The brain dopamine (DA) system participates in forming and expressing memory. Despite a well-established role of DA neurons in the ventral tegmental area in memory formation, the exact DA circuits that control memory expression remain unclear. Here, we show that DA neurons in the dorsal raphe nucleus (DRN) and their medulla input control the expression of incentive memory. DRN DA neurons are activated by both rewarding and aversive stimuli in a learning-dependent manner and exhibit elevated activity during memory recall. Disrupting their physiological activity or DA synthesis blocks the expression of natural appetitive and aversive memories as well as drug memories associated with opioids. Moreover, a glutamatergic pathway from the lateral parabrachial nucleus to the DRN selectively regulates the expression of reward memories associated with opioids or foods. Our study reveals a specialized DA subsystem important for memory expression and suggests new targets for interventions against opioid addiction.

Keywords: addiction; chemogenetics; dorsal raphe; fiber photomery; lateral parabrachial nucleus; memory expression; memory recall; opioids; optogenetics; single-cell reconstruction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dopamine / metabolism
  • Dopaminergic Neurons / drug effects
  • Dopaminergic Neurons / metabolism
  • Dopaminergic Neurons / physiology*
  • Female
  • Glutamic Acid / metabolism
  • Male
  • Memory*
  • Mice
  • Mice, Inbred C57BL
  • Morphine / pharmacology
  • Narcotics / pharmacology
  • Raphe Nuclei / cytology
  • Raphe Nuclei / metabolism
  • Raphe Nuclei / physiology*
  • Reward*


  • Narcotics
  • Glutamic Acid
  • Morphine
  • Dopamine