Inactivation of the Medial Entorhinal Cortex Selectively Disrupts Learning of Interval Timing

James G. Heys, Zihan Wu, Anna Letizia Allegra Mascaro, Daniel A. Dombeck*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


The entorhinal-hippocampal circuit can encode features of elapsed time, but nearly all previous research focused on neural encoding of “implicit time.” Recent research has revealed encoding of “explicit time” in the medial entorhinal cortex (MEC) as mice are actively engaged in an interval timing task. However, it is unclear whether the MEC is required for temporal perception and/or learning during such explicit timing tasks. We therefore optogenetically inactivated the MEC as mice learned an interval timing “door stop” task that engaged mice in immobile interval timing behavior and locomotion-dependent navigation behavior. We find that the MEC is critically involved in learning of interval timing but not necessary for estimating temporal duration after learning. Together with our previous research, these results suggest that activity of a subcircuit in the MEC that encodes elapsed time during immobility is necessary for learning interval timing behaviors.

Original languageEnglish (US)
Article number108163
JournalCell reports
Issue number12
StatePublished - Sep 22 2020


  • hippocampus
  • interval timing
  • learning
  • medial entorhinal cortex
  • memory
  • optogenetic inactivation
  • optogenetic stimulation
  • virtual reality

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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