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The Journal of Neuroscience, October 13, 2004, 24(41):8961-8974; doi:10.1523/JNEUROSCI.2016-04.2004

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Cellular/Molecular
Presynaptic Glycine Receptors on GABAergic Terminals Facilitate Discharge of Dopaminergic Neurons in Ventral Tegmental Area

Jiang-Hong Ye,1 Fushun Wang,1 Kresimir Krnjevic,2 Weizhen Wang,3 Zhi-Gang Xiong,3 and Jingli Zhang1

1Departments of Anesthesiology, Pharmacology, and Physiology, New Jersey Medical School, Newark, New Jersey 07103, 2Physiology Department, McGill University, Montréal, Quebec H3G 1Y6 Canada, and 3Robert S. Dow Neurobiology Laboratories, Legacy Research, Portland, Oregon 97232

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 {omega}-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.

Key words: IPSCs; synaptic transmission; calcium channels; whole-cell patch clamp; strychnine; taurine; mesolimbic system


Received March 9, 2004; revised August 16, 2004; accepted August 16, 2004.




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