Inhibition of medio-dorsal thalamus disrupts thalamo-frontal connectivity and cognition

• Published in: Neuron (Cambridge, Mass.) Mass.), 2013-03, Vol.77 (6), p.1151-1162
• Main Authors: Parnaudeau, S., O'Neill, P.K., Bolkan, S., Ward, R.D., Abbas, A.I., Roth, B.L., Balsam, P., Gordon, J.A., Kellendonk, C.
• Format: Article
• Language: English
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2013.01.038

Cognitive deficits are central to schizophrenia but the underlying mechanisms still remain unclear. Imaging studies performed in patients point to decreased activity in the medio-dorsal 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.