Cholinergic Interneurons Mediate Fast VGluT3-Dependent Glutamatergic Transmission in the Striatum
Cholinergic Interneurons Mediate Fast VGluT3-Dependent Glutamatergic Transmission in the Striatum
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DOI：
10.1371/journal.pone.0019155
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发表时间：
2011-04-22
期刊：
影响因子：
3.7
通讯作者：
Sabatini, Bernardo L.
中科院分区：
文献类型：
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作者：
Higley, Michael J.;Gittis, Aryn H.;Sabatini, Bernardo L.
神经递质谷氨酸是由遍布大脑的兴奋性投射神经元释放的。然而，非谷氨酸能细胞，包括胆碱能和单胺能神经元，表达的标记表明它们也能够囊泡性谷氨酸释放。纹状体胆碱能中间神经元表达3型囊泡型谷氨酸转运体(VGluT3)，但它们是否形成功能性谷氨酸能突触尚不清楚。为了检验这种可能性，我们利用内源性胆碱乙酰转移酶基因座控制下表达Cre重组酶的小鼠，并在CINs中有条件地表达光激活的通道视紫红质2。光刺激诱发CINs的动作电位，并在中等棘神经元产生突触后反应，该反应可被谷氨酸受体拮抗剂阻断。CIN介导的谷氨酸能反应表现出NMDA型谷氨酸受体的很大贡献，将它们与皮质纹状体输入区分开来。CIN介导的谷氨酸能反应对乙酰胆碱受体拮抗剂不敏感，在缺乏VGluT3的小鼠中看不到。我们的结果表明，CINs能够介导快速的谷氨酸能传递，这表明这些细胞在调节纹状体活动中发挥了新的作用。
The neurotransmitter glutamate is released by excitatory projection neurons throughout the brain. However, non-glutamatergic cells, including cholinergic and monoaminergic neurons, express markers that suggest that they are also capable of vesicular glutamate release. Striatal cholinergic interneurons (CINs) express the Type-3 vesicular glutamate transporter (VGluT3), although whether they form functional glutamatergic synapses is unclear. To examine this possibility, we utilized mice expressing Cre-recombinase under control of the endogenous choline acetyltransferase locus and conditionally expressed light-activated Channelrhodopsin2 in CINs. Optical stimulation evoked action potentials in CINs and produced postsynaptic responses in medium spiny neurons that were blocked by glutamate receptor antagonists. CIN-mediated glutamatergic responses exhibited a large contribution of NMDA-type glutamate receptors, distinguishing them from corticostriatal inputs. CIN-mediated glutamatergic responses were insensitive to antagonists of acetylcholine receptors and were not seen in mice lacking VGluT3. Our results indicate that CINs are capable of mediating fast glutamatergic transmission, suggesting a new role for these cells in regulating striatal activity.