Olfactory discrimination learning in mice lacking the fragile X mental retardation protein

Abstract

An automated training system was used to compare the behavior of knockout (KO) mice lacking the Fragile X Mental Retardation Protein with that of wild-type (WT) mice (C57Bl/6 strain) in the acquisition and retention of olfactory discriminations. KO and WT mice did not differ in the acquisition of a four-stage nose poke shaping procedure. In two separate experiments, mutant mice required substantially more training to acquire a series of novel olfactory discrimination problems than did control mice. The KO mice required significantly more sessions to reach criterion performance, made significantly more errors during training, and more often failed to acquire discriminations. Both KO and WT mice showed similar error patterns when learning novel discriminations and both groups showed evidence of more rapid learning of later discriminations in the problem series. Both groups showed significant long-term memory two or four weeks after training but WT and KO mice did not differ in this regard. A group of well-trained mice were given training on novel odors in sessions limited to 20-80 trials. Memory of these problems at two day delays did not differ between WT and KO mice. Tests using ethyl acetate demonstrated that WT and KO mice had similar odor detection thresholds.

Fragile X mice have robust mGluR5-dependent alterations of social behaviour in the Automated Tube Test

“…Undoubtedly, social behaviour is a widely distributed function that requires coordinated function across a large diversity of brain regions (O'Connell and Hofmann, 2012;Rushworth et al, 2013;Timmer et al, 2011;van der Kooij and Sandi, 2012). Moreover, since olfactory discrimination is normal in Fmr1 KO animals (Larson et al, 2008) and because of the lack of differences in training data between WT and Fmr1 KO animals, we feel comfortable in the conclusion that the observed phenotypes are related directly to social behaviour, Fig. 4.…”

Metabotropic Glutamate Receptors as Therapeutic Targets for Cognitive Disorders

“…Further, deficits in executive functioning, and both declarative and procedural learning have been observed in an FXS patient [133]. Similarly, learning and memory impairments have also been observed in Fmr1 mutant mice [129,[134][135][136][137]. According to the mGluR theory of FXS (Fig.…”

Behavioral and physiological characterization of PKC-dependent phosphorylation in the Grin2a∆PKC mouse

“…This schedule was also used to stably maintain their reduced body weight (target weight) throughout the training. After all the animals reached their target weight, they were trained in an enclosed testing chamber made of black acrylic that consisted of an alley measuring 60 cm × 10 cm as described previously (Larson et al, 2008). Briefly, a shaping procedure was used at the end of which a mouse was familiarized to the apparatus and also to reinforce nose-poke responses in either sniff-port.…”