In cases in which normal distribution

of data could be assumed (p > MLN0128 chemical structure 0.05), the parametric two-tailed Student’s t test was employed to compare means. For testing the statistical significance of the deviation of the proportion of values compared to equal distribution, the χ2 test was applied. A p value of p < 0.05 was considered significant. The authors thank Jia Lou for help with preparing the figures, Sarah Bechtold and Rosa Karl for virus preparation, Rebecca Mease for help with data analysis, Rita Förster for perfusion of mice, and the other laboratory members for critical comments on the manuscript. This work was supported by the Friedrich Schiedel Foundation and by the European Commission under the 7th Framework Programme, Project Corticonic. S. Fischer and C. Rühlmann were supported by the DFG (IRTG 1373). A. Konnerth designed the study. A. Stroh and GS-7340 C. Rühlmann performed the viral construct injections and confocal imaging. A. Stroh, C. Rühlmann, A. Schierloh, and H. Adelsberger performed the optical fiber recordings. S. Fischer and H. Adelsberger conducted and analyzed the camera recordings. A. Groh and A. Stroh conducted the electrophysiological measurements. A. Stroh and K. Deisseroth established the optogenetic procedures. A. Konnerth and A. Stroh wrote the manuscript.

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“Schizophrenia is a devastating mental disorder characterized by three clusters of symptoms: positive symptoms (psychosis and thought disorder), negative symptoms (social and emotional deficits), and cognitive Phosphoprotein phosphatase symptoms. Understanding the cognitive symptoms of schizophrenia is of particular significance because they are highly predictive for the long-term

prognosis of the disease, and at present they are essentially resistant to treatment (Green, 1996). Cognitive symptoms include deficits in working memory and behavioral flexibility (Forbes et al., 2009; Leeson et al., 2009), two processes of executive function that are essential for activities of daily living. Functional magnetic resonance imaging studies have consistently shown an association between impaired executive function and altered activity in the prefrontal cortex (PFC) of patients, leading to the influential hypothesis that prefrontal dysfunction underlies the cognitive symptoms of schizophrenia (Weinberger and Berman, 1996). Due to its dense excitatory reciprocal connection with the PFC (Jones, 2007), the mediodorsal thalamus (MD) has become a focus of attention in the study of cognitive symptoms. Imaging studies have repeatedly shown decreased activation of the MD in patients under a variety of test conditions that address executive functions (Andrews et al., 2006; Minzenberg et al., 2009). Altered correlation between activity in the MD and the PFC at rest or during cognitive testing has also been observed (Minzenberg et al., 2009; Mitelman et al., 2005; Woodward et al., 2012).