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Dopamine synapse is a neuroligin-2-mediated contact between dopaminergic presynaptic and GABAergic postsynaptic structures
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| Title: | Dopamine synapse is a neuroligin-2-mediated contact between dopaminergic presynaptic and GABAergic postsynaptic structures |
| Other Titles: | Heterologous contact at dopamine synapses |
| Authors: | Uchigashima, Motokazu Browse this author →KAKEN DB | | Ohtsuka, Toshihisa Browse this author →KAKEN DB | | Kobayashi, Kazuto Browse this author →KAKEN DB | | Watanabe, Masahiko Browse this author →KAKEN DB |
| Keywords: | dopamine synapse | | neuroligin-2 | | medium spiny neuron | | striatum |
| Issue Date: | 12-Apr-2016 |
| Publisher: | National Academy of Sciences |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 113 |
| Issue: | 15 |
| Start Page: | 4206 |
| End Page: | 4211 |
| Publisher DOI: | 10.1073/pnas.1514074113 |
| 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 GABA(A) receptor alpha 1, 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. |
| Rights: | http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/63004 |
| Appears in Collections: | 医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 渡邉 雅彦
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