Behavioral and neural responses to high-strength magnetic fields are reduced in otolith mutant mice.

Static high magnetic fields (MFs) interact with the vestibular system of humans and rodents. In rats and mice, exposure to MFs causes perturbations such as head movements, circular locomotion, suppressed rearing, nystagmus, and conditioned taste aversion acquisition. To test the role of otoconia, two mutant mouse models were examined, head-tilt Nox3het (het) and tilted Otop1 (tlt), with mutations, respectively, in Nox3, encoding the NADPH oxidase 3 enzyme, and Otop1, encoding the otopetrin 1 proton channel, which are normally expressed in the otolith organs, and are critical for otoconia formation. Consequently, both mutants show a near complete loss of otoconia in the utricle and saccule, and are nonresponsive to linear acceleration. Mice were exposed to a 14.1 Tesla MF for 30 min. After exposure, locomotor activity, conditioned taste aversion and c-Fos (in het) were assessed. Wild-type mice exposed to the MF showed suppressed rearing, increased latency to rear, locomotor circling, and c-Fos in brainstem nuclei related to vestibular processing (prepositus, spinal vestibular, and supragenual nuclei). Mutant het mice showed no response to the magnet and were similar to sham animals in all assays. Unlike het, tlt mutants exposed to the MF showed significant locomotor circling and suppressed rearing compared with sham controls, although they failed to acquire a taste aversion. The residual responsiveness of tlt versus het mice might reflect a greater semicircular deficit in het mice. These results demonstrate the necessity of the otoconia for the full effect of exposure to high MFs, but also suggest a semicircular contribution.

Variability and uncertainty in the rodent controlled cortical impact model of traumatic brain injury.

BACKGROUND: Controlled cortical impact (CCI) has emerged as one of the most flexible and clinically applicable approaches for the induction of traumatic brain injury (TBI) in rodents and other species. Although this approach has been shown to model cognitive and functional outcomes associated with TBI in humans, recent work has shown that CCI is limited by excessive variability in lesion size despite attempts to control velocity, impact depth, and dwell time. NEW METHOD: Thus, this work used high-speed imaging to evaluate the delivery of cortical impact and permit the identification of specific parameters associated with technical variability in the CCI model. RESULTS: Variability is introduced by vertical oscillations that result in multiple impacts of varying depths, lateral movements after impact, and changes in velocity, particularly at the prescribed impact depth. CONCLUSIONS: Together these data can inform future work to design modifications to commonly used CCI devices that produce TBI with less variability in severity and lesion size.