Expression and action of secretin in rat cerebellar deep nuclei neurons

Abstract

We recently reported that secretin and its receptors are expressed in the cerebellum of the rat [1] and human [2] . Electrophysiologically, secretin modulates the inhibitory neurotransmission from basket cells to Purkinje neurons. However, despite the fact that Purkinje neurons express secretin receptor mRNA, secretin administration does not evoke any postsynaptic responses in these cells. These observations suggest that Purkinje neurons may synthesize secretin receptors and transport them to nerve terminals in the deep nuclei. To test this hypothesis, we examined the expression of secretin and secretin receptors in the cerebellar deep nuclei of rats and studied the electrophysiological actions of secretin on GABAergic neurotransmission from Purkinje neurons to deep nuclei neurons. By means of in situ hybridization, deep nuclei neurons were found to express both secretin and secretin receptor mRNA. In agreement with this observation, immunohistochemical staining showed strong expression of secretin in the same type of neurons. Furthermore, administration of 30 n M of secretin increased the frequency of TTX-resistant, or miniature, inhibitory postsynaptic currents by 61.6% in 14 cells (p ! 0.05) while the amplitudes were not affected. These data suggest that secretin released by deep nuclei neurons activate presynaptic secretin receptors on the terminals of Purkinje neurons. Therefore, secretin appears to modulate the activity of the cerebellum by acting at multiple levels of inhibitory synapses in the cerebellar circuit. Acknowledgement: Supported by the National Natural Science Foundation of China and the Research Grants Council of Hong Kong (N_CUHK 427/03).