Abstract
Cerebellar outputs from the deep cerebellar nuclei (DCN) are critical to the generation and control of movement. Activity of DCN neurons is mainly controlled by GABAergic inhibitory transmission of Purkinje cells in the cerebellar cortex and is also modulated by nerve inputs originated from other brain regions in and out of the cerebellum. Serotonergic nerve fibers originated from the dorsal raphe nuclei has been known to send their input onto DCN. In this study, therefore, we examined modulatory effects of serotonin (5-HT) on GABAergic synapses in the DCN. We found that 5-HT decreased the amplitude of stimulation-evoked IPSCs (eIPSC) in DCN neurons, and their effect was abolished by a 5-HT1B antagonist, SB224289. The decrease in IPSCs amplitude was associated with increase in paired-pulse ratio of eIPSC. 5-HT also decreased the frequency of miniature IPSCs without changing their amplitude. These data suggested that 5-HT presynaptically inhibited the eIPSC amplitude. Furthermore, slow inward currents were observed in DCN neurons during 5-HT application. Pharmacological studies revealed that 5-HT possibly activated 5-HT5 receptor positively coupled to G-protein and elicited slow inward current through acceleration of Ih channel at the membrane of DCN neurons. In summary, 5-HT released onto DCN may pre- and post-synaptically play a regulatory role in the spike generation and the gain control of inhibitory GABAergic synapses, thereby promoting the voluntary activity in DCN neurons themselves. [J Physiol Sci. 2008;58 Suppl:S126]
