Local release of monoamines in the cerebellar cortex

The cerebellum is classically associated with coordination and motor learning. Yet, a growing body of evidence now indicates that the cerebellum also contributes to cognitive aspects including social behavior and navigation skills. Although monoamines such as noradrenaline (NE) and dopamine (DA) are key neuromodulators implicated in these cognitive functions, the modus operandi of monoaminergic systems and their relevance to cerebellar functioning remains poorly understood. Interestingly, we found that while in this brain region monoaminergic innervations are sparse, the main vesicular transporter of monoamines VMAT2 is expressed in both Bergmann glial cells, the most abundant cell type of the cerebellum, and Purkinje neurons, the neuronal output of the cerebellar cortex. Our study thus aims at investigating the role of Purkinje neurons and Bergmann glia in the control of monoaminergic transmission. Our current results indicate that many proteins of the monoaminergic system are expressed in the cerebellar cortex, and particularly in Purkinje cells and Bergmann glia. By using viral constructs that express genetically encoded NE and DA fluorescent sensors (GRAB-NE and GRAB-DA), we were able to visualize spontaneous extracellular release events of DA and NE in acute cerebellar cortex slices, via 2-photons imaging. Importantly, pharmacological and chemogenetic activation of Bergmann glia increases the size, shape, and frequency of the spontaneous release events of DA and NE. Taken together, these results strongly suggest a role for Bergmann glia in regulating monoamines homeostasis in the cerebellar cortex.