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.
authors.affiliation: Department of Psychiatry, New York State Psychiatric Institute, New York, NY 10032, USA.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Parnaudeau
authors.forename: Pia-Kelsey
authors.initials: PK
authors.lastname: O'Neill
authors.forename: Scott S
authors.initials: SS
authors.lastname: Bolkan
authors.forename: Ryan D
authors.initials: RD
authors.lastname: Ward
authors.forename: Atheir I
authors.initials: AI
authors.lastname: Abbas
authors.forename: Bryan L
authors.initials: BL
authors.lastname: Roth
authors.forename: Peter D
authors.initials: PD
authors.lastname: Balsam
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Gordon
authors.forename: Christoph
authors.initials: C
authors.lastname: Kellendonk
mesh_terms: D000818:Animals; D003071:Cognition / Q000502:physiology*; D008297:Male; D020645:Mediodorsal Thalamic Nucleus / Q000502:physiology*; D008570:Memory, Short-Term / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009433:Neural Inhibition / Q000502:physiology*; D009434:Neural Pathways / Q000502:physiology; D017397:Prefrontal Cortex / Q000502:physiology*; D011597:Psychomotor Performance / Q000502:physiology*