It has recently been shown that a lack of vestibular sensory information decreases spatial memory performance and induces biochemical changes in the hippocampus in rodents. After vestibular neurectomy, patients display spatial memory deficit and hippocampal atrophy. Our objectives were to explore: (a) spatial (Y maze, radial-arm maze), and non-spatial (object recognition) memory performance, (b) modulation of NMDA receptors within the hippocampus using radioligand binding, and (c) hippocampal atrophy, using MRI, in a rat model of bilateral labyrinthectomy realized in two operations. Chemical vestibular lesions (VLs) were induced in 24 animals by transtympanic injections of sodium arsanilate (30 mg/0.1 ml/ear), one side being lesioned 3 weeks after the other. The control group received transtympanic saline solution (0.1 ml/ear) (n = 24). Spatial memory performance (Y maze and radial maze) decreased after VL. Conversely, non-spatial memory performance (object recognition) was not affected by VL. No hippocampal atrophy was observed with MRI, but density of NMDA receptors were increased in the hippocampus after VL. These findings show that the lack of vestibular information induced specific deficits in spatial memory. Additionally, quantitative autoradiographic data suggest the involvement of the glutamatergic system in spatial memory processes related to vestibular information. When studying spatial memory performances in the presence of vestibular syndrome, two-step labyrinthectomy is a suitable procedure for distinguishing between the roles of the specific components of vestibular input loss and those of impaired locomotor activity.

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Mineralization of the skeleton depends on the balance between levels of pyrophosphate (PPi), an inhibitor of hydroxyapatite formation, and phosphate generated from PPi breakdown by alkaline phosphatase (ALP). We report here that ablation of Nf1, encoding the RAS/GTPase–activating protein neurofibromin, in bone–forming cells leads to supraphysiologic PPi accumulation, caused by a chronic ERK–dependent increase in genes promoting PPi synthesis and extracellular transport, namely Enpp1 and Ank. It also prevents BMP2–induced osteoprogenitor differentiation and, consequently, expression of ALP and PPi breakdown, further contributing to PPi accumulation. The short stature, impaired bone mineralization and strength in mice lacking Nf1 in osteochondroprogenitors or osteoblasts could be corrected by enzyme therapy aimed at reducing PPi concentration. These results establish neurofibromin as an essential regulator of bone mineralization, suggest that altered PPi homeostasis contributes to the skeletal dysplasiae associated with neurofibromatosis type-1 (NF1), and that some of the NF1 skeletal conditions might be preventable pharmacologically.