Presynaptic Serotonergic gating of the subthalamonigral glutamatergic projection

Shengyuan Ding, Li Li, Fuming Zhou

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

The GABAergic projection neurons in the substantia nigra pars reticulata (SNr) are key basal ganglia output neurons. The activity of these neurons is critically influenced by the glutamatergic projection from the subthalamic nucleus (STN). The SNr also receives an intense serotonin (5-HT) innervation, raising the possibility that 5-HT may regulate the STN→SNr glutamatergic transmission and the consequent STN-triggered spike firing in SNr neurons. Here we show that 5-HT reduced STN stimulation-evoked long-lasting polysynaptic complex EPSCs in SNr GABA neurons. This inhibitory 5-HT effect was mimicked by the 5-HT1B receptor agonist CP93129 and blocked by the 5-HT1B antagonist NAS-181. 5-HT1A receptor ligands were ineffective. Additionally, 5-HT and CP93129 reduced the frequency but not the amplitude of miniature EPSCs, suggesting a reduced vesicular release. 5-HT and CP93129 also decreased the amplitude but increased the paired pulse ratio of the monosynaptic EPSCs in SNr GABA neurons, indicating a presynaptic 5-HT1B receptor-mediated inhibition of glutamate release. Furthermore, 5-HT and CP93129 inhibited STN-triggered burst firing in SNr GABA neurons, and CP93129's inhibitory effect was strongest when puffed to STN→SNr axon terminals in SNr, indicating a primary role of the 5-HT1B receptors in these axon terminals. Finally, the 5-HT1B receptor antagonist NAS-181 increased the STN-triggered complex EPSCs and burst firing in SNr GABA neurons, demonstrating the effects of endogenous 5-HT. These results suggest that nigral 5-HT, via presynaptic 5-HT1B receptor activation, gates the excitatory STN→SNr projection, reduces burst firing in SNr GABA neurons, and thus may play a critical role in movement control.

Original languageEnglish (US)
Pages (from-to)4875-4885
Number of pages11
JournalJournal of Neuroscience
Volume33
Issue number11
DOIs
StatePublished - Mar 13 2013

Fingerprint

Serotonin
GABAergic Neurons
Receptor, Serotonin, 5-HT1B
Subthalamic Nucleus
Serotonin 5-HT1 Receptor Antagonists
Presynaptic Terminals
Neurons
Serotonin 5-HT1 Receptor Agonists
Pars Reticulata
Receptor, Serotonin, 5-HT1A
Substantia Nigra
Basal Ganglia
Glutamic Acid
Ligands

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Presynaptic Serotonergic gating of the subthalamonigral glutamatergic projection. / Ding, Shengyuan; Li, Li; Zhou, Fuming.

In: Journal of Neuroscience, Vol. 33, No. 11, 13.03.2013, p. 4875-4885.

Research output: Contribution to journalArticle

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