Transient expression of functional serotonin 5-HT3 receptors by glutamatergic granule cells in the early postnatal mouse cerebellum

The Journal of Physiology The serotonin 5-HT3 receptor is the only ligand-gated ion channel activated by serotonin and is expressed by GABAergic interneurons in many brain regions, including the cortex, amygdala and hippocampus. Furthermore, 5-HT3 receptors are expressed by glutamatergic Cajal-Retzius cells in the cerebral cortex. We used 5-HT3A/enhanced green fluorescent protein (EGFP) transgenic mice to show that 5-HT3 receptors are also ubiquitously expressed by glutamatergic granule cells in the cerebellum during the first three postnatal weeks. Using whole-cell patch clamp recordings, we show that local application of either serotonin or the selective 5-HT3 receptor agonist SR57227A to granule cells results in a small inward current, demonstrating a post- and/or extrasynaptic localisation of the 5-HT3 receptors. Functional 5-HT3 receptors were also observed presynaptically at the parallel fibre-Purkinje cell synapse. Pharmacological block using the selective 5-HT3 receptor antagonist tropisetron induced a reduction in the frequency of miniature synaptic events recorded from Purkinje cells. Paired-pulse stimulation of parallel fibres on whole-cell voltage clamped Purkinje cells from 1-week-old mice did not yet show synaptic plasticity. In the presence of tropisetron, the parallel fibre-Purkinje cell synapse showed paired-pulse depression. Taken together, these results show that functional 5-HT3 receptors are present during early postnatal development in the cerebellum, where they modulate synaptic plasticity.