Distinct Temporal Expression of 5-HT(1A) and 5-HT(2A) Receptors on Cerebellar Granule Cells in Mice

Serotonin plays an important role of controlling the physiology of the cerebellum. However, serotonin receptor expression has not been fully studied in the developing cerebellum. We have recently shown that cerebellar granule cells transiently express 5-HT(3) receptors. In the present study, we investigate expression of 5-HT(1) and 5-HT(2) receptors in the mouse cerebellum both during postnatal development and in juvenile mice. Here, we show for the first time that 5-HT(1A) and 5-HT(2A) receptors are present on cerebellar granule cells with a distinct temporal expression pattern: 5-HT(1A) receptors are expressed only during the first 2 weeks, while 5-HT(2A) receptor expression persists until at least 8 weeks after birth. Because of its prolonged expression pattern, we investigated the electrophysiological properties of the 5-HT(2A) receptor. 5-HT(2A) receptors expressed by cerebellar granule cells promote stability by reducing variability of the synaptic response, and they modulate the paired-pulse ratio of the parallel fibre–Purkinje cell synapse. Furthermore, pharmacological block of 5-HT(2A) receptors enhances short-term synaptic plasticity at the parallel fibre–Purkinje cell synapse. We thus show a novel role for serotonin in controlling function of the cerebellum via 5-HT(2A) receptors expressed by cerebellar granule cells.