Thalamic projections sustain prefrontal activity during working memory maintenance.

Autor: Bolkan SS; Columbia University, College of Physicians and Surgeons, New York, New York, USA., Stujenske JM; Columbia University, College of Physicians and Surgeons, New York, New York, USA., Parnaudeau S; Institut de Biologie Paris Seine, UM119, Neuroscience Paris Seine, CNRS UMR8246, INSERM U1130, Paris, France., Spellman TJ; Research Institute, Weill Cornell Medical College, New York, New York, USA., Rauffenbart C; Department of Psychiatry, Columbia University, College of Physicians and Surgeons, New York, New York, USA.; Department of Pharmacology, Columbia University, College of Physicians and Surgeons, New York, New York, USA.; Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, New York, USA., Abbas AI; Department of Psychiatry, Columbia University, College of Physicians and Surgeons, New York, New York, USA.; Division of Integrative Neuroscience, New York State Psychiatric Institute, New York, New York, USA., Harris AZ; Department of Psychiatry, Columbia University, College of Physicians and Surgeons, New York, New York, USA.; Division of Integrative Neuroscience, New York State Psychiatric Institute, New York, New York, USA., Gordon JA; Department of Psychiatry, Columbia University, College of Physicians and Surgeons, New York, New York, USA.; Division of Integrative Neuroscience, New York State Psychiatric Institute, New York, New York, USA.; National Institute of Mental Health, Office of the Director, Bethesda, Maryland, USA., Kellendonk C; Department of Psychiatry, Columbia University, College of Physicians and Surgeons, New York, New York, USA.; Department of Pharmacology, Columbia University, College of Physicians and Surgeons, New York, New York, USA.; Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, New York, USA.
Jazyk: angličtina
Zdroj: Nature neuroscience [Nat Neurosci] 2017 Jul; Vol. 20 (7), pp. 987-996. Date of Electronic Publication: 2017 May 03.
DOI: 10.1038/nn.4568
Abstrakt: 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.
Databáze: MEDLINE
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