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

doi:10.1016/j.neuron.2013.01.038

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Inhibition of mediodorsal thalamus disrupts thalamofrontal connectivity and cognition

Journal article

Open access

Peer reviewed

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 and Christoph Kellendonk

Neuron (Cambridge, Mass.), Vol.77(6), pp.1151-1162

03/20/2013

DOI: 10.1016/j.neuron.2013.01.038

PMCID: PMC3629822

PMID: 23522049

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https://doi.org/10.1016/j.neuron.2013.01.038View

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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.

Animals

Cognition - physiology

Male

Mediodorsal Thalamic Nucleus - physiology

Memory, Short-Term - physiology

Mice

Mice, Inbred C57BL

Neural Inhibition - physiology

Neural Pathways - physiology

Prefrontal Cortex - physiology

Psychomotor Performance - physiology

Details

Title: Subtitle: Inhibition of mediodorsal thalamus disrupts thalamofrontal connectivity and cognition
Creators: Sebastien Parnaudeau - New York Psychoanalytic Society and Institute
Pia-Kelsey O'Neill
Scott S Bolkan - Columbia University
Ryan D Ward - New York State Psychiatric Institute
Atheir I Abbas - New York Psychoanalytic Society and Institute
Bryan L Roth - University of North Carolina at Chapel Hill
Peter D Balsam - New York State Psychiatric Institute
Joshua A Gordon - New York Psychoanalytic Society and Institute
Christoph Kellendonk - Columbia University
Resource Type: Journal article
Publication Details: Neuron (Cambridge, Mass.), Vol.77(6), pp.1151-1162
DOI: 10.1016/j.neuron.2013.01.038
PMID: 23522049
PMCID: PMC3629822
NLM abbreviation: Neuron
ISSN: 0896-6273
eISSN: 1097-4199
Grant note: R01 MH061887 / NIMH NIH HHS R01 MH081968 / NIMH NIH HHS U19 MH082441 / NIMH NIH HHS T32 GM007250 / NIGMS NIH HHS R25 MH086466 / NIMH NIH HHS R01 MH096274 / NIMH NIH HHS T32 HD007430 / NICHD NIH HHS U19MH82441 / NIMH NIH HHS R21 MH093887 / NIMH NIH HHS
Language: English
Date published: 03/20/2013
Academic Unit: Psychological and Brain Sciences
Record Identifier: 9984945143602771

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