Heterozygous mice with Ric-8 mutation exhibit impaired spatial memory and decreased anxiety.
Ric-8 is a guanine nucleotide exchange factor for a subset of Galpha proteins and it is required to maintain Galpha(q) and the Galpha(s) pathways in functional state. In adult mice Ric-8 is expressed in regions involved in the regulation of behavior (neocortex, cingulate cortex and hippocampus). As Ric-8 is shown to regulate neuronal transmitter release, the aim of present study was to perform behavioral analysis of ric-8 mutant. Homozygous (-/-) ric-8 mutant mice are not viable and die in early embryonic development, therefore for behavioral analysis heterozygous (+/-) ric-8 mutant mice were used. We found decreased anxiety of ric-8 heterozygous mice in light-dark compartment test where mutant mice significantly avoided the light compartment. In spatial learning paradigm (Morris water maze) the performance of ric-8 (+/-) mice was impaired. Namely, in the reversal test, ric-8 (+/-) mice exhibited significant delay to find the hidden platform compared to wild-type (wt) littermates. We did not find differences in the behavioral tests reflecting the motor abilities of mice (motor activity, rota-rod). Therefore, described alterations seem to be specific for anxiety and spatial learning. Based on these results we can conclude the importance of ric-8 in the regulation of memory and emotional behavior.
Tõnissoo
Tambet
T
Department of Integrative Zoology, University of Tartu, 46 Vanemuise St., Tartu 51014, Estonia.
Kõks
Sulev
S
Meier
Riho
R
Raud
Sirli
S
Plaas
Mario
M
Vasar
Eero
E
Karis
Alar
A
D000818:Animals; D001007:Anxiety / Q000235:genetics*; D001522:Behavior, Animal / Q000502:physiology; D005106:Exploratory Behavior / Q000502:physiology; D005260:Female; D005697:Galactosides / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors; D006624:Hippocampus / Q000473:pathology; D007211:Indoles / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics; D009154:Mutation; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics*; D017966:Pyramidal Cells / Q000473:pathology; D011930:Reaction Time / Q000235:genetics; D045442:Rotarod Performance Test / Q000379:methods; D013037:Spatial Behavior / Q000502:physiology*
D005697:Galactosides; D020662:Guanine Nucleotide Exchange Factors; D007211:Indoles; D009687:Nuclear Proteins; C485884:Ric8a protein, mouse; C044888:5-bromo-4-chloro-3-indolyl beta-galactoside