Behavioral characterization of mice lacking the neurite outgrowth inhibitor Nogo-A.
The membrane protein Nogo-A inhibits neurite outgrowth and regeneration in the injured central nervous system, primarily because of its expression in oligodendrocytes. Hence, deletion of Nogo-A enhances regeneration following spinal cord injury. Yet, the effects of Nogo-A deletion on general behavior and cognition have not been explored. The possibility of potential novel functions of Nogo-A beyond growth inhibition is strongly suggested by the presence of subpopulations of neurons also expressing Nogo-A - not only during development but also in adulthood. We evaluated here Nogo-A(-/-) mice in a series of general basic behavioral assays as well as functional analyses related to brain regions with notable expression levels of Nogo-A. The SHIRPA protocol did not show any major basic behavioral changes in Nogo-A(-/-) mice. Anxiety-related behavior, pain sensitivity, startle reactivity, spatial learning, and associative learning also appeared indistinguishable between Nogo-A(-/-) and control Nogo-A(+/+) mice. However, motor co-ordination and balance were enhanced in Nogo-A(-/-) mice. Spontaneous locomotor activity was also elevated in Nogo-A(-/-) mice, but this was specifically observed in the dark (active) phase of the circadian cycle. Enhanced locomotor reaction to systemic amphetamine in Nogo-A(-/-) mice further pointed to an altered dopaminergic tone in these mice. The present study is the first behavioral characterization of mice lacking Nogo-A and provides significant insights into the potential behavioral relevance of Nogo-A in the modulation of dopaminergic and motor functions.
Willi
R
R
Brain Research Institute, University of Zurich, Zurich, Switzerland. rwilli@hifo.uzh.ch
Aloy
E M
EM
Yee
B K
BK
Feldon
J
J
Schwab
M E
ME
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001007:Anxiety / Q000235:genetics / Q000523:psychology; D001245:Association Learning / Q000502:physiology; D001362:Avoidance Learning / Q000502:physiology; D001522:Behavior, Animal / Q000502:physiology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D002531:Cerebellum / Q000166:cytology / Q000502:physiology; D002940:Circadian Rhythm / Q000235:genetics / Q000502:physiology; D007031:Hypothalamus / Q000166:cytology / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics / Q000502:physiology; D009185:Myelin Proteins / Q000235:genetics*; D009474:Neurons / Q000502:physiology; D000070798:Nogo Proteins; D010147:Pain Measurement; D004856:Postural Balance / Q000502:physiology; D011597:Psychomotor Performance / Q000502:physiology; D013216:Reflex, Startle / Q000502:physiology; D012165:Retinal Ganglion Cells / Q000502:physiology
D000697:Central Nervous System Stimulants; D009185:Myelin Proteins; D000070798:Nogo Proteins; C000603201:Rtn4 protein, mouse; D000661:Amphetamine