Center for Molecular and Behavioral Neuroscience, Rutgers University, Newark, New Jersey 07102, USA.
J Neurosci. 2010 May 19;30(20):7105-10. doi: 10.1523/JNEUROSCI.0265-10.2010.
Recent evidence suggests the intriguing possibility that midbrain dopaminergic (DAergic) neurons may use fast glutamatergic transmission to communicate with their postsynaptic targets. Because of technical limitations, direct demonstration of the existence of this signaling mechanism has been limited to experiments using cell culture preparations that often alter neuronal function including neurotransmitter phenotype. Consequently, it remains uncertain whether glutamatergic signaling between DAergic neurons and their postsynaptic targets exists under physiological conditions. Here, using an optogenetic approach, we provide the first conclusive demonstration that mesolimbic DAergic neurons in mice release glutamate and elicit excitatory postsynaptic responses in projection neurons of the nucleus accumbens. In addition, we describe the properties of the postsynaptic glutamatergic responses of these neurons during experimentally evoked burst firing of DAergic axons that reproduce the reward-related phasic population activity of the mesolimbic projection. These observations indicate that, in addition to DAergic mechanisms, mesolimbic reward signaling may involve glutamatergic transmission.
最近的证据表明，一种有趣的可能性是中脑多巴胺能（DAergic）神经元可能使用快速谷氨酸能传递与它们的突触后靶标进行通讯。由于技术限制，直接证明这种信号机制的存在仅限于使用细胞培养制剂进行的实验，这些实验往往改变神经元功能，包括神经递质表型。因此，尚不确定在生理条件下，DAergic 神经元与其突触后靶标之间是否存在谷氨酸能信号传递。在这里，我们使用光遗传学方法首次明确证明，在小鼠中，中脑边缘 DAergic 神经元释放谷氨酸，并在伏隔核的投射神经元中引发兴奋性突触后反应。此外，我们描述了在实验诱发的 DAergic 轴突爆发放电期间这些神经元的突触后谷氨酸能反应的特性，这种放电再现了中脑边缘投射的与奖励相关的相位群活动。这些观察结果表明，除了 DAergic 机制之外，中脑边缘奖励信号传递可能涉及谷氨酸能传递。
