High frequency stimulation of the ventrolateral and mediodorsal thalamic nuclei: differential effects on impulsive action

Abstract

Ventrolateral thalamic nucleus stimulation is a frequently applied clinical procedure to control disabling tremor. Its motor effects are largely established now, but the cognitive effects are largely unknown and are currently under investigation. Here, we performed a detailed investigation of the effects of electrical stimulation at high frequency (130 Hz) and various amplitude (0, 1, 3, 30, 150) of the VL thalamic nucleus in a rat model on specific cognitive functions, using a reaction time task, and compared to DBS of the mediodorsal thalamic nucleus (MD) to evaluate the specificity of the site of stimulation. The involvement of the MD thalamic nucleus in cognitive functions has already been established. In addition, we mapped the effect of VL and MD thalamic nuclei DBS on the neuronal activity of the mPFC using c-Fos immunohistochemistry to investigate the neural pathways underlying the behavioural effects. Results show that DBS of the VL and MD thalamic nuclei had no significant effects on reaction time and motor time. DBS of the VL thalamic nucleus induced no significant effect on premature responding, whereas DBS of the MD thalamic nucleus increased this. In addition, MD and VL thalamic nuclei DBS significantly increased the number of c-Fos-immunoreactive cells in the prelimbic cortex as compared to control animals. In the infralimbic cortex, the number of c-Fos-immunoreactive cells was significantly higher following MD thalamic nucleus DBS as compared to the other groups. These findings support that the VL thalamic nuclei is not involved in impulsive action. However, DBS of the MD thalamic nucleus induced specific changes in cognitive parameters, which further establishes its involvement in behavioral functions.. This behavioral effect is mediated by a circuit involving specific prefrontal cortical areas.

Keywords

• Deep brain stimulation c-Fos, Mediodorsal thalamic nucleus, Premature responding, Reaction time task, Ventrolateral thalamic nucleusRat

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