Median raphe controls acquisition of negative experience in the mouse

Science. 2019 Nov 29;366(6469):eaay8746. doi: 10.1126/science.aay8746.


Adverse events need to be quickly evaluated and memorized, yet how these processes are coordinated is poorly understood. We discovered a large population of excitatory neurons in mouse median raphe region (MRR) expressing vesicular glutamate transporter 2 (vGluT2) that received inputs from several negative experience-related brain centers, projected to the main aversion centers, and activated the septohippocampal system pivotal for learning of adverse events. These neurons were selectively activated by aversive but not rewarding stimuli. Their stimulation induced place aversion, aggression, depression-related anhedonia, and suppression of reward-seeking behavior and memory acquisition-promoting hippocampal theta oscillations. By contrast, their suppression impaired both contextual and cued fear memory formation. These results suggest that MRR vGluT2 neurons are crucial for the acquisition of negative experiences and may play a central role in depression-related mood disorders.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aggression / physiology*
  • Anhedonia / physiology*
  • Animals
  • Avoidance Learning / physiology*
  • Depression / physiopathology
  • Dorsal Raphe Nucleus / metabolism
  • Dorsal Raphe Nucleus / physiology*
  • Evoked Potentials / physiology
  • Habenula / physiology
  • Hippocampus / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neurons / metabolism
  • Optogenetics
  • Theta Rhythm
  • Vesicular Glutamate Transport Protein 2 / genetics
  • Vesicular Glutamate Transport Protein 2 / metabolism*


  • Slc17a6 protein, mouse
  • Vesicular Glutamate Transport Protein 2

Associated data

  • figshare/10.6084/m9.figshare.8924771.v1