Full length articleA microstructural analysis distinguishes motor and motivational influences over voluntary running in animals chronically exposed to methylmercury and nimodipine

- An analysis of response bouts can separate motor and motivational effects on behavior.
- Chronic methylmercury exposure negatively impacted motor-related parameters.
- Nimodipine dose-dependently protected from methylmercury effects.
- Nimodipine protection supports the role of calcium dysregulation in MeHg toxicity.

Adult-onset methylmercury (MeHg) exposure produces sensorimotor impairment and related changes in behavior. The present study investigated MeHg effects on the microstructure of spontaneous wheel running in adult BALB/c mice chronically exposed to 0 ppm or 15 ppm MeHg via daily drinking water. To test the hypothesis that MeHg neurotoxicity is related to impaired calcium homeostasis, MeHg-exposed mice received 0, 20, or 200 ppm of the L-type calcium-channel blocker nimodipine in their daily chow diet. To examine MeHg-related changes in the microstructure of running, we partitioned spontaneous wheel running into activity epochs using a change-point algorithm and derived estimates of the within-bout response rate (primarily a motor-function measure), the duration of pausing between bouts (primarily a motivation measure), and the length of response bouts (a hybrid measure) from those epochs. Mice also performed regular rotarod sessions, providing a second measure of motor coordination. MeHg impaired rotarod performance and nimodipine dose-dependently mitigated that effect. MeHg decreased the distance run and within-bout running rate, especially during the final weeks of exposure and nimodipine attenuated and delayed that impairment. The interbout interval was only slightly but significantly affected by MeHg with no evidence of decline at the end of exposure and no influence of nimodipine. Despite the presence of impaired running, there was no evidence of fatigue through the course of long, three-hour sessions. These findings suggest that the microstructure of behavior provides sensitive and interpretable measures of MeHg effects, support the utility of bout analysis for separating motor and motivational effects of drug and toxicant exposure, and show selective neuroprotection by nimodipine.