Inhibition of Mediodorsal Thalamus Disrupts Thalamofrontal Connectivity and Cognition

Sebastien Parnaudeau, Pia Kelsey O'Neill, Scott S. Bolkan, Ryan D. Ward, Atheir I. Abbas, Bryan L. Roth, Peter D. Balsam, Joshua A. Gordon, Christoph Kellendonk

Research output: Contribution to journalArticlepeer-review

201 Scopus citations

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

Original languageEnglish (US)
Pages (from-to)1151-1162
Number of pages12
JournalNeuron
Volume77
Issue number6
DOIs
StatePublished - Mar 20 2013
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)

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