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Proc Natl Acad Sci U S A. 2016 Apr 12;113(15):4206-11. doi: 10.1073/pnas.1514074113. Epub 2016 Mar 25.

Dopamine synapse is a neuroligin-2-mediated contact between dopaminergic presynaptic and GABAergic postsynaptic structures.

Author information

1
Department of Anatomy, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan;
2
Department of Biochemistry, Graduate School of Medicine, University of Yamanashi, Chuo 409-3898, Japan;
3
Department of Molecular Genetics, Institute of Biomedical Sciences, Fukushima Medical University, Fukushima 960-1295, Japan.
4
Department of Anatomy, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan; watamasa@med.hokudai.ac.jp.

Abstract

Midbrain dopamine neurons project densely to the striatum and form so-called dopamine synapses on medium spiny neurons (MSNs), principal neurons in the striatum. Because dopamine receptors are widely expressed away from dopamine synapses, it remains unclear how dopamine synapses are involved in dopaminergic transmission. Here we demonstrate that dopamine synapses are contacts formed between dopaminergic presynaptic and GABAergic postsynaptic structures. The presynaptic structure expressed tyrosine hydroxylase, vesicular monoamine transporter-2, and plasmalemmal dopamine transporter, which are essential for dopamine synthesis, vesicular filling, and recycling, but was below the detection threshold for molecules involving GABA synthesis and vesicular filling or for GABA itself. In contrast, the postsynaptic structure of dopamine synapses expressed GABAergic molecules, including postsynaptic adhesion molecule neuroligin-2, postsynaptic scaffolding molecule gephyrin, and GABAA receptor α1, without any specific clustering of dopamine receptors. Of these, neuroligin-2 promoted presynaptic differentiation in axons of midbrain dopamine neurons and striatal GABAergic neurons in culture. After neuroligin-2 knockdown in the striatum, a significant decrease of dopamine synapses coupled with a reciprocal increase of GABAergic synapses was observed on MSN dendrites. This finding suggests that neuroligin-2 controls striatal synapse formation by giving competitive advantage to heterologous dopamine synapses over conventional GABAergic synapses. Considering that MSN dendrites are preferential targets of dopamine synapses and express high levels of dopamine receptors, dopamine synapse formation may serve to increase the specificity and potency of dopaminergic modulation of striatal outputs by anchoring dopamine release sites to dopamine-sensing targets.

KEYWORDS:

dopamine synapse; medium spiny neuron; neuroligin-2; striatum

PMID:
27035941
PMCID:
PMC4839454
DOI:
10.1073/pnas.1514074113
[Indexed for MEDLINE]
Free PMC Article

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