Thalamic projections sustain prefrontal activity during working memory maintenance

Nat Neurosci. 2017 Jul;20(7):987-996. doi: 10.1038/nn.4568. Epub 2017 May 3.


The mediodorsal thalamus (MD) shares reciprocal connectivity with the prefrontal cortex (PFC), and decreased MD-PFC connectivity is observed in schizophrenia patients. Patients also display cognitive deficits including impairments in working memory, but a mechanistic link between thalamo-prefrontal circuit function and working memory is missing. Using pathway-specific inhibition, we found directional interactions between mouse MD and medial PFC (mPFC), with MD-to-mPFC supporting working memory maintenance and mPFC-to-MD supporting subsequent choice. We further identify mPFC neurons that display elevated spiking during the delay, a feature that was absent on error trials and required MD inputs for sustained maintenance. Strikingly, delay-tuned neurons had minimal overlap with spatially tuned neurons, and each mPFC population exhibited mutually exclusive dependence on MD and hippocampal inputs. These findings indicate a role for MD in sustaining prefrontal activity during working memory maintenance. Consistent with this idea, we found that enhancing MD excitability was sufficient to enhance task performance.

MeSH terms

  • Action Potentials / physiology
  • Animals
  • Choice Behavior / physiology*
  • Hippocampus / physiology
  • Humans
  • Male
  • Maze Learning / physiology
  • Memory, Short-Term / physiology*
  • Mice
  • Neural Pathways / physiology
  • Neurons / physiology
  • Prefrontal Cortex / physiology*
  • Spatial Memory / physiology
  • Thalamus / physiology*
  • Time Factors