Hippocampal-prefrontal theta-gamma coupling during performance of a spatial working memory task

Nat Commun. 2017 Dec 19;8(1):2182. doi: 10.1038/s41467-017-02108-9.


Cross-frequency coupling supports the organization of brain rhythms and is present during a range of cognitive functions. However, little is known about whether and how long-range cross-frequency coupling across distant brain regions subserves working memory. Here we report that theta-slow gamma coupling between the hippocampus and medial prefrontal cortex (mPFC) is augmented in a genetic mouse model of cognitive dysfunction. This increased cross-frequency coupling is observed specifically when the mice successfully perform a spatial working memory task. In wild-type mice, increasing task difficulty by introducing a long delay or by optogenetically interfering with encoding, also increases theta-gamma coupling during correct trials. Finally, epochs of high hippocampal theta-prefrontal slow gamma coupling are associated with increased synchronization of neurons within the mPFC. These findings suggest that enhancement of theta-slow gamma coupling reflects a compensatory mechanism to maintain spatial working memory performance in the setting of increased difficulty.

Publication types

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

MeSH terms

  • Animals
  • Cognitive Dysfunction / diagnosis
  • Cognitive Dysfunction / physiopathology*
  • Cortical Synchronization / physiology
  • Disease Models, Animal
  • Electrodes
  • Female
  • Gamma Rhythm / physiology*
  • Hippocampus / cytology
  • Hippocampus / physiology*
  • Humans
  • Male
  • Memory, Short-Term / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Neural Pathways / physiology
  • Neurons / physiology
  • Optogenetics
  • Prefrontal Cortex / cytology
  • Prefrontal Cortex / physiology*
  • Theta Rhythm / physiology*