Complexin II is essential for normal neurological function in mice.
Complexins (CPLXs) are modulators of synaptic vesicle release. At 1 year of age, CPLXII knockout (KO) mice appear normal. However, behavioral testing reveals underlying deficits of motor and cognitive function in these mice. We found motor deficits on the rotarod, and learning deficits in the Morris water maze (both acquisition and reversal) and the two-choice swim tank (reversal). The reversal learning deficits are particularly noticeable, being present from the earliest time of testing, when most other behaviors are normal. CPLXII KO mice also fail to develop adult patterns of exploratory behavior in the open field and show deficits in interactive grooming behaviors. The behavioral deficits worsen with age. For example, while rotarod performance is normal until 10 weeks, it is impaired from 24 weeks onwards. Similarly, deficits in spatial learning in the Morris water maze are mild at 8 weeks, but pronounced by 1 year of age. The deficits seen in CPLXII KO mice are not due to physical weakness, since their ability to run, swim and grip is unimpaired. Rather, the mice appear to have deficits of higher function. The deficits seen in CPLXII KO mice are strikingly similar to those seen in the R6/2 model of Huntington's disease (HD) where a progressive depletion of CPLXII is seen. This suggests that depletion of CPLXII contributes to cognitive abnormalities in R6/2 mice. Given that decreased expression of CPLXII is seen in HD and schizophrenic patients, a role for CPLXII depletion should be considered in other diseases where motor, cognitive and psychiatric symptoms co-exist.
Glynn
Dervila
D
Department of Pharmacology, University of Cambridge, UK.
Bortnick
Rachel A
RA
Morton
A Jennifer
AJ
D033942:Adaptor Proteins, Vesicular Transport; D000375:Aging; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D001835:Body Weight; D003072:Cognition Disorders / Q000235:genetics; D006120:Grooming; D006720:Homozygote; D007859:Learning Disabilities / Q000235:genetics; D018782:Maze Learning; D008569:Memory Disorders / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000502:physiology*; D011597:Psychomotor Performance; D013028:Space Perception; D013550:Swimming; D013997:Time Factors; D014796:Visual Perception / Q000235:genetics
D033942:Adaptor Proteins, Vesicular Transport; D009419:Nerve Tissue Proteins; C095993:complexin II