Impaired recruitment of dopamine neurons during working memory in mice with striatal D2 receptor overexpression

Nat Commun. 2018 Jul 19;9(1):2822. doi: 10.1038/s41467-018-05214-4.


The dopamine (DA) system plays a major role in cognitive functions through its interactions with several brain regions including the prefrontal cortex (PFC). Conversely, disturbances in the DA system contribute to cognitive deficits in psychiatric diseases, yet exactly how they do so remains poorly understood. Here we show, using mice with disease-relevant alterations in DA signaling (D2R-OE mice), that deficits in working memory (WM) are associated with impairments in the WM-dependent firing patterns of DA neurons in the ventral tegmental area (VTA). The WM-dependent phase-locking of DA neurons to 4 Hz VTA-PFC oscillations is absent in D2R-OE mice and VTA-PFC synchrony deficits scale with their WM impairments. We also find reduced 4 Hz synchrony between VTA DA neurons and selective impairments in their representation of WM demand. These results identify how altered DA neuron activity-at the level of long-range network activity and task-related firing patterns-may underlie cognitive impairments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / physiology
  • Animals
  • Cell Movement
  • Cognitive Dysfunction / genetics*
  • Cognitive Dysfunction / metabolism
  • Cognitive Dysfunction / physiopathology
  • Corpus Striatum / metabolism*
  • Corpus Striatum / physiopathology
  • Dopamine / metabolism
  • Dopaminergic Neurons / metabolism*
  • Dopaminergic Neurons / pathology
  • Electrodes, Implanted
  • Gene Expression
  • Male
  • Maze Learning / physiology
  • Memory, Short-Term*
  • Mice
  • Mice, Transgenic
  • Neural Pathways / metabolism
  • Neural Pathways / physiopathology
  • Prefrontal Cortex / metabolism*
  • Prefrontal Cortex / physiopathology
  • Receptors, Dopamine D2 / genetics*
  • Receptors, Dopamine D2 / metabolism
  • Stereotaxic Techniques
  • Up-Regulation
  • Ventral Tegmental Area / metabolism
  • Ventral Tegmental Area / physiopathology


  • Receptors, Dopamine D2
  • Dopamine