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Front Behav Neurosci. 2014 Mar 18;8:90. doi: 10.3389/fnbeh.2014.00090. eCollection 2014.

Nogo-A-deficient Transgenic Rats Show Deficits in Higher Cognitive Functions, Decreased Anxiety, and Altered Circadian Activity Patterns.

Author information

1
Department of Neurophysiology of Memory, Institute of Physiology, Academy of Sciences of the Czech Republic , Prague , Czech Republic ; First Faculty of Medicine, Charles University in Prague , Prague , Czech Republic.
2
Department of Neurophysiology of Memory, Institute of Physiology, Academy of Sciences of the Czech Republic , Prague , Czech Republic.
3
Department of Neurohumoral Regulations, Institute of Physiology, Academy of Sciences of the Czech Republic , Prague , Czech Republic.
4
Department of Neurophysiology of Memory, Institute of Physiology, Academy of Sciences of the Czech Republic , Prague , Czech Republic ; Social Psychology, Department of Psychology II, University of Würzburg , Würzburg , Germany.
5
Department of Molecular Biology, Central Institute of Mental Health , Mannheim , Germany.
6
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.
7
Brain Research Institute, University of Zurich , Zurich , Switzerland ; Neurosciences, Department of Biology, Swiss Federal Institute of Technology Zurich , Zurich , Switzerland.

Abstract

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.

KEYWORDS:

AAPA; Carousel maze; Nogo-A; anhedonia; circadian rhythmicity; neophobia; passive avoidance

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