Decreased levels of Nogo-A-dependent signaling have been shown to affect behavior and cognitive functions. In Nogo-A knockout and knockdown laboratory rodents, behavioral alterations were observed, possibly corresponding with human neuropsychiatric diseases of neurodevelopmental origin, particularly schizophrenia. This study offers further insight into behavioral manifestations of Nogo-A knockdown in laboratory rats, focusing on spatial and non-spatial cognition, anxiety levels, circadian rhythmicity, and activity patterns. Demonstrated is an impairment of cognitive functions and behavioral flexibility in a spatial active avoidance task, while non-spatial memory in a step-through avoidance task was spared. No signs of anhedonia, typical for schizophrenic patients, were observed in the animals. Some measures indicated lower anxiety levels in the Nogo-A-deficient group. Circadian rhythmicity in locomotor activity was preserved in the Nogo-A knockout rats and their circadian period (tau) did not differ from controls. However, daily activity patterns were slightly altered in the knockdown animals. We conclude that a reduction of Nogo-A levels induces changes in CNS development, manifested as subtle alterations in cognitive functions, emotionality, and activity patterns.

Brain Research Institute University of Zurich Zurich Switzerland ; Neurosciences Department of Biology Swiss Federal Institute of Technology Zurich Zurich Switzerland

Brain Research Institute University of Zurich Zurich Switzerland ; Neurosciences Department of Biology Swiss Federal Institute of Technology Zurich Zurich Switzerland ; Division of Molecular Mechanisms of Tumor Invasion German Cancer Research Center Heidelberg Germany

Department of Molecular Biology Central Institute of Mental Health Mannheim Germany

Department of Neurohumoral Regulations Institute of Physiology Academy of Sciences of the Czech Republic Prague Czech Republic

Department of Neurophysiology of Memory Institute of Physiology Academy of Sciences of the Czech Republic Prague Czech Republic

Department of Neurophysiology of Memory Institute of Physiology Academy of Sciences of the Czech Republic Prague Czech Republic ; 1st Faculty of Medicine Charles University Prague Prague Czech Republic

Department of Neurophysiology of Memory Institute of Physiology Academy of Sciences of the Czech Republic Prague Czech Republic ; Social Psychology Department of Psychology 2 University of Würzburg Würzburg Germany

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Chronic MK-801 Application in Adolescence and Early Adulthood: A Spatial Working Memory Deficit in Adult Long-Evans Rats But No Changes in the Hippocampal NMDA Receptor Subunits

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Cognitive deficits in schizophrenia and other neuropsychiatric disorders: convergence of preclinical and clinical evidence