Regulation of the striatal network by glutamate and acetylcholine co-transmission.

谷氨酸和乙酰胆碱共同传递对纹状体网络的调节。

• 批准号: RGPIN-2017-04682
• 负责人: elmestikawy, salah
• 金额: $ 1.82万
• 依托单位: McGill University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=630495
• 关键词: Regulation; striatal; network; glutamate; acetylcholine

Neurons communicate with electrochemical signals. Chemical messengers, or neurotransmitters, are accumulated inside synaptic vesicles (SV) before their calcium-dependent release. Glutamate (glut) the major excitatory transmitter in the brain is concentrated inside SV by vesicular transporter named VGLUT1-3. Our team made the surprising discovery that VGLUT3 is expressed by neurons using other neurotransmitters than glutamate. VGLUT3 is present used by all striatal cholinergic interneurons (also named Tonically Active Neurons or TANS). Therefore, TANS signal with both acetylcholine (ACh) and glut. The consequences of ACh/glut cotransmission recently started to be investigated. For example, we established that VGLUT3 null mice are hyperactive and more sensitive to cocaine. This is essentially due to an increased dopamine signaling in the nucleus accumbens in the absence of VGLUT3. Interestingly, silencing ACh signaling in TANS by specific ablation of the vesicular ACh transporter (VAChT) has opposite effects. Therefore, the dual ACh/glut transmission provides TANS with complex regulatory properties of striatal networks.

神经元通过电化学信号进行交流。化学信使或神经递质在依赖钙释放之前积聚在突触小泡(SV)内。谷氨酸(Glut)是大脑中主要的兴奋性递质，通过称为VGLUT1-3的囊泡转运蛋白集中在SV内。我们的团队做出了令人惊讶的发现，VGLUT3是由神经元使用谷氨酸以外的其他神经递质表达的。VGLUT3目前被所有纹状体胆碱能中间神经元(也称为张力活性神经元或TANS)所使用。因此，TANS与乙酰胆碱(ACh)和Glut一起发出信号。ACh/Glut共传播的后果最近开始被调查。例如，我们证实了VGLUT3基因缺失的小鼠是过度活跃的，对可卡因更敏感。这主要是由于伏隔核多巴胺信号在缺乏VGLUT3的情况下增加所致。有趣的是，通过特异性消融囊泡ACh转运体(Vacht)来沉默TAN中的ACh信号具有相反的效果。因此，双重ACh/GLUT传递为TANS提供了纹状体网络的复杂调节特性。