Dopaminergic inputs in the dentate gyrus direct the choice of memory encoding

Proc Natl Acad Sci U S A. 2016 Sep 13;113(37):E5501-10. doi: 10.1073/pnas.1606951113. Epub 2016 Aug 29.


Rewarding experiences are often well remembered, and such memory formation is known to be dependent on dopamine modulation of the neural substrates engaged in learning and memory; however, it is unknown how and where in the brain dopamine signals bias episodic memory toward preceding rather than subsequent events. Here we found that photostimulation of channelrhodopsin-2-expressing dopaminergic fibers in the dentate gyrus induced a long-term depression of cortical inputs, diminished theta oscillations, and impaired subsequent contextual learning. Computational modeling based on this dopamine modulation indicated an asymmetric association of events occurring before and after reward in memory tasks. In subsequent behavioral experiments, preexposure to a natural reward suppressed hippocampus-dependent memory formation, with an effective time window consistent with the duration of dopamine-induced changes of dentate activity. Overall, our results suggest a mechanism by which dopamine enables the hippocampus to encode memory with reduced interference from subsequent experience.

Keywords: channelrhodopsin-2; dopamine; temporal difference learning; theta oscillation.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Choice Behavior / physiology
  • Dentate Gyrus / metabolism*
  • Dentate Gyrus / physiology
  • Dopamine / metabolism*
  • Dopaminergic Neurons / metabolism
  • Hippocampus / metabolism*
  • Hippocampus / physiology
  • Learning / physiology
  • Memory / physiology*
  • Memory, Episodic
  • Mental Recall / physiology
  • Mice
  • Mice, Transgenic
  • Neuronal Plasticity / genetics
  • Neuronal Plasticity / physiology
  • Reward


  • Dopamine