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

Thalamic projections sustain prefrontal activity during working memory maintenance.

Author information

1
Columbia University, College of Physicians and Surgeons, New York, New York, USA.
2
Institut de Biologie Paris Seine, UM119, Neuroscience Paris Seine, CNRS UMR8246, INSERM U1130, Paris, France.
3
Research Institute, Weill Cornell Medical College, New York, New York, USA.
4
Department of Psychiatry, Columbia University, College of Physicians and Surgeons, New York, New York, USA.
5
Department of Pharmacology, Columbia University, College of Physicians and Surgeons, New York, New York, USA.
6
Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, New York, USA.
7
Division of Integrative Neuroscience, New York State Psychiatric Institute, New York, New York, USA.
8
National Institute of Mental Health, Office of the Director, Bethesda, Maryland, USA.

Abstract

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.

Comment in

PMID:
28481349
PMCID:
PMC5501395
DOI:
10.1038/nn.4568
[Indexed for MEDLINE]
Free PMC Article

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