Lammel Stephan, Hetzel Andrea, Häckel Olga, Jones Ian, Liss Birgit, Roeper Jochen
Institute of Neurophysiology, Neuroscience Center, Goethe-University Frankfurt, Frankfurt 60590, Germany.
Neuron. 2008 Mar 13;57(5):760-73. doi: 10.1016/j.neuron.2008.01.022.
The mesocorticolimbic dopamine system is essential for cognitive and emotive brain functions and is thus an important target in major brain diseases like schizophrenia, drug addiction, and attention deficit hyperactivity disorder. However, the cellular basis for the diversity in behavioral functions and associated dopamine-release pattern within the mesocorticolimbic system has remained unclear. Here, we report the identification of a type of dopaminergic neuron within the mesocorticolimbic dopamine system with unconventional fast-firing properties and small DAT/TH mRNA expression ratios that selectively projects to prefrontal cortex and nucleus accumbens core and medial shell as well as to basolateral amygdala. In contrast, well-described conventional slow-firing dopamine midbrain neurons only project to the lateral shell of the nucleus accumbens and the dorsolateral striatum. Among this dual dopamine midbrain system defined in this study by converging anatomical, electrophysiological, and molecular properties, mesoprefrontal dopaminergic neurons are unique, as only they do not possess functional somatodendritic Girk2-coupled dopamine D2 autoreceptors.
中脑皮质边缘多巴胺系统对大脑的认知和情感功能至关重要，因此是精神分裂症、药物成瘾和注意力缺陷多动障碍等主要脑部疾病的重要靶点。然而，中脑皮质边缘系统内行为功能多样性及相关多巴胺释放模式的细胞基础仍不清楚。在此，我们报告在中脑皮质边缘多巴胺系统中鉴定出一种具有非常规快速放电特性且多巴胺转运体/酪氨酸羟化酶mRNA表达比率小的多巴胺能神经元，其选择性投射至前额叶皮质、伏隔核核心及内侧壳以及基底外侧杏仁核。相比之下，已被充分描述的传统慢放电多巴胺中脑神经元仅投射至伏隔核外侧壳和背外侧纹状体。在本研究通过整合解剖学、电生理学和分子特性定义的这种双重多巴胺中脑系统中，中前额叶多巴胺能神经元是独特的，因为只有它们不具备功能性的树突体Girk2偶联多巴胺D2自身受体。
