Elsevier

Neuroscience

Volume 172, 13 January 2011, Pages 118-128
Neuroscience

Cellular and Molecular Neuroscience
Modulatory effects of serotonin on glutamatergic synaptic transmission and long-term depression in the deep cerebellar nuclei

https://doi.org/10.1016/j.neuroscience.2010.10.037Get rights and content

Abstract

The deep cerebellar nuclei (DCN) are the terminal components of the cerebellar circuitry and constitute its primary output structure. Their activity is important for certain forms of motor learning as well as generation and control of movement. DCN neurons receive glutamatergic excitatory inputs from the pontine nuclei via mossy fibres (MFs) and concomitantly receive inputs from 5-HT-containing neurons of the raphe nuclei. We aimed to explore the roles of 5-HT at MF–DCN synapses by using cerebellar slices from 11 to 15-day-old rats. Bath application of 5-HT reversibly decreased the amplitude of stimulation-evoked excitatory postsynaptic currents (eEPSCs) via the activation of 5-HT1B receptors at the presynaptic terminals of the MFs. Burst stimulation of the MFs elicited long-term depression (LTD) at the MF–DCN synapses that require activation of the group I metabotropic glutamate receptor (mGluR). In the presence of 5-HT, the extent of burst-induced LTD of MF EPSCs was significantly reduced. Application of 5-HT also decreased the amplitude of mGluR-dependent slow EPSCs evoked by similar burst stimulation. Furthermore, (S)-3,5-dihydroxyphenylglycine (DHPG), a group I mGluR agonist, induced chemical LTD of MF EPSCs, and 5-HT had no significant effect on this LTD. Taken together, the results suggest that 5-HT not only has transitory inhibitory effects on MF EPSCs but also plays a role in regulating the long-term synaptic efficacy.

Research Highlights

▶Serotonin (5-HT) presynaptically suppressed glutamate release at mossy fibre-deep cerebellar nuclei (MF-DCN) synapses by 5-HT1B receptor activation. ▶5-HT also decreased the amplitude of the mGluR-mediated slow EPSC. ▶In the presence of 5-HT, magnitude of LTD of MF EPSC amplitude was reduced, resulting from the suppression of mGluR activation. ▶5-HT not only has transitory inhibitory effects on MF EPSCs but also plays a role in regulating the long-term synaptic efficacy.

Section snippets

Slice preparation

Experiments were performed by using cerebellar slices from Wistar rats (Saitow et al., 2005) aged 11–15 days. According to a protocol approved by the Ethics Review Committee of Nippon Medical School (approval number: H20-021 and H21-064), we made effort for minimizing the number of animals used and their suffering. Animals of both genders were deeply anaesthetized through halothane inhalation (∼2% in air, v/v), and their brains were rapidly removed. Parasagittal slices of 250 μm thickness were

Glutamatergic excitatory synaptic currents in DCN neurons

In the presence of 50 μM picrotoxin, which was used to block GABAergic transmission, electrical stimulation via the glass microelectrodes in the white matter produced EPSCs in the DCN neurons (Fig. 1B), at a membrane potential (Vh) of −70 mV. A paired pulse with 50 ms interpulse intervals elicited stimulation-evoked EPSCs (eEPSCs). AMPA receptor antagonist CNQX (10 μM) largely blocked these eEPSCs, and additional application of specific NMDA receptor antagonist D-APV (40 μM) completely blocked

Discussion

Here, we have shown that 5-HT can modulate glutamatergic synaptic transmission and synaptic plasticity in the DCN. Firstly, 5-HT reduced the amplitude of glutamatergic EPSCs through the activation of presynaptic 5-HT1B receptors. Secondly, it reduced the magnitude of the LTD of the EPSCs. The reduction was induced by the suppression of mGluR activation, probably because of the decreased release probability of glutamate from MF synaptic terminals. These results suggest that in the DCN, 5-HT is

Conclusion

The present study, together with our previous study, reveals 5-HT modulations of synaptic transmission and plasticity at the DCN. Overall, 5-HT might decrease the synaptic effects by acting on both excitatory and inhibitory inputs and thereby control the output information from the cerebellum.

Acknowledgments

We thank Drs. Katsunori Kobayashi and Moritoshi Hirono for their invaluable comments and critical reading of this manuscript. This work was supported by a Grant-in-Aid for Scientific Research (21500375) and grants (S0801035) from the MEXT, Japan (F.S. and H.S.), and CREST, Japan Science and Technology Agency, Japan (F.S. and H.S.).

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