Presynaptic glycine receptors on GABAergic terminals facilitate discharge of dopaminergic neurons in ventral tegmental area

Jiang Hong Ye, Fushun Wang, Kresimir Krnjević, Weizhen Wang, Zhi Gang Xiong, Jingli Zhang

Research output: Contribution to journalArticlepeer-review

73 Scopus citations

Abstract

GABA-mediated postsynaptic currents (IPSCs) were recorded from dopaminergic (DA) neurons of the ventral tegmental area (VTA) of rats, in acute brain slices, and from enzymatically or mechanically dissociated neurons. In young rats (3-10 d of age), where GABA is excitatory, glycine (1-3 μM) and taurine (10-30 μM) increased the amplitude of evoked IPSCs (eIPSCs) and the frequency of spontaneous IPSCs (sIPSCs) but had minimal postsynaptic effects. Strychnine (1 μM) blocked the action of glycine; when applied alone, it reduced the amplitude of eIPSCs and the frequency of sIPSCs, indicating a tonic facilitation of GABAergic excitation by some endogenous glycine agonist(s). In medium containing no Ca2+, or with Cd2+ or tetrodotoxin added, the amplitude and especially the frequency of sIPSCs greatly diminished. In many cells, glycine had no effect on remaining miniature IPSCs, suggesting a preterminal site of glycine receptors (GlyRs). Fura-2 fluorescent imaging showed a glycine-induced increase of [Ca2+] in nerve terminals (on DA neurons), which was suppressed by strychnine or 3 μM ω-conotoxin MVIIA. Therefore, the presynaptic GlyR-mediated facilitation of GABAergic transmission seems to be mediated by N- and/or P/Q-type Ca2+ channels. In older rats (22-30 d of age), where GABA causes inhibition, the effect of strychnine on GABAergic IPSCs was reversed to facilitation, indicating a tonic glycinergic inhibition of GABA release. Furthermore, glycine (1-3 μM) reduced the amplitude of eIPSCs and the frequency of sIPSCs. Hence, the overall effect of the presynaptic action of glycine is to enhance the firing of DA cells, both in very young and older rats.

Original languageEnglish (US)
Pages (from-to)8961-8974
Number of pages14
JournalJournal of Neuroscience
Volume24
Issue number41
DOIs
StatePublished - Oct 13 2004

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Keywords

  • Calcium channels
  • IPSCs
  • Mesolimbic system
  • Strychnine
  • Synaptic transmission
  • Taurine
  • Whole-cell patch clamp

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