@article{4e4a1c6228544b1b82668f2057c97363,
title = "Inhibition of Mediodorsal Thalamus Disrupts Thalamofrontal Connectivity and Cognition",
abstract = "Cognitive deficits are central to schizophrenia, but the underlying mechanisms still remain unclear. Imaging studies performed in patients point to decreased activity in the mediodorsal thalamus (MD) and reduced functional connectivity between the MD and prefrontal cortex (PFC) as candidate mechanisms. However, a causal link is still missing. We used a pharmacogenetic approach in mice to diminish MD neuron activity and examined the behavioral and physiological consequences. We found that a subtle decrease in MD activity is sufficient to trigger selective impairments in prefrontal-dependent cognitive tasks. In vivo recordings in behaving animals revealed that MD-PFC beta-range synchrony is enhanced during acquisition and performance of a working memory task. Decreasing MD activity interfered with this task-dependent modulation of MD-PFC synchrony, which correlated with impaired working memory. These findings suggest that altered MD activity is sufficient to disrupt prefrontal-dependent cognitive behaviors and could contribute to the cognitive symptoms observed in schizophrenia",
author = "Sebastien Parnaudeau and O'Neill, {Pia Kelsey} and Bolkan, {Scott S.} and Ward, {Ryan D.} and Abbas, {Atheir I.} and Roth, {Bryan L.} and Balsam, {Peter D.} and Gordon, {Joshua A.} and Christoph Kellendonk",
note = "Funding Information: We would like to thank Neil Harrison for advising on in vitro slice physiology and Mariya Shegda for excellent technical help. CNO was obtained from the NIH as part of the Rapid Access to Investigative Drug Program funded by the NINDS. This work was supported by grants from “Anonymous Foundation” and NARSAD to C.K., from the International Mental Health Research Organization, the Hope for Depression Research Foundation, and the NIH (R21 MH093887 and R01 MH081968) to J.A.G, U19MH82441 to B.L.R., and a Fondation Fyssen Fellowship to S.P. A.I.A. is a Leon Levy Foundation Resident Fellow and is supported by R25 MH086466. S.P. designed and performed the experiments, conducted the data analysis, and wrote the paper. P.K.O. performed the in vivo recordings experiment and conducted the analysis. S.S.B. and R.D.W. helped with behavior experiments. A.I.A. assisted in the analysis of the in vivo recordings. B.L.R. provided the DREADD system. P.B. supervised and designed behavioral experiments. J.A.G. and C.K. designed and supervised the performance of the experiments and data analysis and wrote the paper. ",
year = "2013",
month = mar,
day = "20",
doi = "10.1016/j.neuron.2013.01.038",
language = "English (US)",
volume = "77",
pages = "1151--1162",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "6",
}