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

神经元通过电化学信号进行交流。化学信使或神经递质在其钙依赖性释放之前积聚在突触囊泡（SV）内。谷氨酸（glut）是脑内主要的兴奋性递质，通过称为VGLUT 1 -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，VGLUT 3是由神经元使用其他神经递质而不是谷氨酸表达的。VGLUT 3被所有纹状体胆碱能中间神经元（也称为紧张性活性神经元或TNS）使用。因此，TANS信号与乙酰胆碱（ACh）和glut。ACh/过量共传递的后果最近开始调查。例如，我们确定VGLUT 3缺失小鼠是过度活跃的，对可卡因更敏感。这基本上是由于在VGLUT 3不存在的情况下，丘脑核中多巴胺信号传导增加。有趣的是，沉默乙酰胆碱信号在TANS特异性消融囊泡乙酰胆碱转运蛋白（VAChT）有相反的效果。因此，ACh/glut的双重传递为TANS提供了纹状体网络的复杂调节特性。

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.