High frequency stimulation of the anterior vermis modulates behavioural response to chronic stress: involvement of the prefrontal cortex and dorsal raphe?

Some evidence suggests that the cerebellum modulates affect via connectivities with mood-regulating corticolimbic structures, such as the prefrontal cortex and monoamine nuclei. In rats exposed to chronic unpredictable stress (CUS), we examined the neuro-behavioural effects of high frequency stimulation and surgical ablation/disconnection of the cerebellar vermis. CUS reduced sucrose preference, increased novelty-induced feeding suppression and passive coping. These depressive-like behaviours were associated with decreased cerebellar zif268 expression, indicating possible cerebellar involvement in stress pathology. These were paralleled by decreased vermal Purkinje simple and complex spiking activity and raphe serotonergic activity. Protracted (24-h) vermal stimulation reversed these behavioural deficits through serotonin-mediated mechanisms since this effect was abrogated by the serotonin-depleting agent pCPA. Vermal stimulation and disconnection lesion also enhanced serotonergic activity, but did not modify prefrontocortical pyramidal firing. This effect was likely mediated by 5-HT1A receptors (5-HT1AR). Indeed, acute vermal stimulation mimicked the effect of the 5-HT1AR agonist 8-OH-DPAT in inhibiting serotonergic activity, which was prevented by pre-treatment with the 5-HT1AR antagonist WAY100,635. These results demonstrate vermal involvement in depressive-type behaviour via its modulatory action on serotonergic neurons. They further suggest that vermal and mPFC stimulation may bestow therapeutic benefits via parallel pathways.