Cerebellar Bergmann glia integrate noxious information and modulate nocifensive behaviors

Abstract

The cerebellum is activated by noxious stimuli and pathological pain but its role in noxious information processing remains unknown. Here, we show that in mice, cutaneous noxious electrical stimuli induced noradrenaline (NA) release from locus coeruleus (LC) terminals in the cerebellar cortex. Bergmann glia (BG) accumulated these LC-NA signals by increasing intracellular calcium in an integrative manner ('flares'). BG flares were also elicited in response to an intraplantar capsaicin injection. Chemogenetic inactivation of LC terminals or BG in the cerebellar cortex or BG-specific knockdown of α₁-adrenergic receptors suppressed BG flares, reduced nocifensive licking and had analgesic effects in nerve injury-induced chronic neuropathic pain. Moreover, chemogenetic activation of BG or an intraplantar capsaicin injection reduced Purkinje cell firing, which may disinhibit the output activity of the deep cerebellar nuclei. These results suggest a role for BG in computing noxious information from the LC and in modulating pain-related behaviors by regulating cerebellar output.