Abstract

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-HT3 receptors. In the present study, we investigate expression of 5-HT1 and 5-HT2 receptors in the mouse cerebellum both during postnatal development and in juvenile mice. Here, we show for the first time that 5-HT1A and 5-HT2A receptors are present on cerebellar granule cells with a distinct temporal expression pattern: 5-HT1A receptors are expressed only during the first 2 weeks, while 5-HT2A receptor expression persists until at least 8 weeks after birth. Because of its prolonged expression pattern, we investigated the electrophysiological properties of the 5-HT2A receptor. 5-HT2A 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-HT2A 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-HT2A receptors expressed by cerebellar granule cells.

Highlights

  • Serotonin plays an important role of controlling the physiology of the cerebellum

  • We show for the first time that functional 5-HT1A and 5-HT2A receptors are expressed by cerebellar granule cells during early postnatal development. 5HT1A receptors are transiently expressed during the first 2 weeks postnatally, while 5-HT2A receptors remain present on granule cells until 10 weeks of age

  • Because of the temporal restriction of 5-HT1A receptors on cerebellar granule cells to the first 10 days postnatally and because of the sustained expression of 5-HT2A receptors, the functional role of 5-HT2A receptors on granule cells was studied in more detail

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Summary

Introduction

Serotonin plays an important role of controlling the physiology of the cerebellum. serotonin receptor expression has not been fully studied in the developing cerebellum. We show a novel role for serotonin in controlling function of the cerebellum via 5-HT2A receptors expressed by cerebellar granule cells. We have recently shown that 5-HT3 receptors are transiently expressed by cerebellar granule cells in mice during early postnatal development [12]. We hypothesized that other members of the serotonergic system in the cerebellum co-regulate cerebellar development and are functional at time points surrounding the transient expression pattern of 5-HT3 receptors. This happens presumably by switching to other types of serotonin receptors expressed in the cerebellum during postnatal development and thereafter. Other studies done on adult rodents did not reveal the presence of 5-HT2 receptors on cerebellar granule cells [18, 25]

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