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Retrograde labeling illuminates distinct topographical organization of D1 and D2 receptor-positive neurons in the prefrontal cortex of mice.
bioRxiv - Neuroscience Pub Date : 2020-08-10 , DOI: 10.1101/2020.05.04.077792
Sara M. Green , Sanya Nathani , Joseph Zimmerman , David Fireman , Nikhil M. Urs

The cortex plays an important role in regulating motivation and cognition, and does so by regulating multiple subcortical brain circuits. Glutamatergic pyramidal neurons in the prefrontal cortex (PFC) are topographically organized in different subregions such as the prelimbic, infralimbic and orbitofrontal, and project to topographically-organized subcortical target regions. Dopamine D1 and D2 receptors are expressed on glutamatergic pyramidal neurons in the PFC. However, it is unclear whether D1 and D2 receptor-expressing pyramidal neurons in the PFC are also topographically organized. We used a retrograde adeno-associated virus (AAVRG)-based approach to illuminate the topographical organization of D1 and D2 receptor-expressing neurons, projecting to distinct striatal and midbrain subregions. Our experiments reveal that AAVRG injection in the nucleus accumbens (NAcc) or dorsal striatum (dSTR) of D1Cre mice labeled distinct neuronal subpopulations in medial orbitofrontal or prelimbic PFC, respectively. However, AAVRG injection in NAcc or dSTR of D2Cre mice labeled medial orbitofrontal, but not medial prelimbic PFC, respectively. Additionally, D2R+ but not D1R+ PFC neurons were labeled upon injection of AAVRG in substantia nigra pars compacta (SNpc). Thus, our data are the first to highlight a unique dopamine receptor-specific topographical pattern in the PFC, which could have profound implications for cortico-striatal signaling in the basal ganglia.

中文翻译:

逆行标记阐明了小鼠前额叶皮层中D1和D2受体阳性神经元的独特地形组织。

皮层在调节动机和认知中起着重要作用,并通过调节多个皮层下大脑回路来发挥作用。前额叶皮层(PFC)中的谷氨酸能锥体神经元在地形上组织在不同的子区域中,例如前缘,下缘和眶额叶,并投射到地形上组织的皮层下目标区域。多巴胺D1和D2受体在PFC中的谷氨酸能锥体神经元上表达。但是,尚不清楚PFC中表达D1和D2受体的锥体神经元是否在地形上也有组织。我们使用了基于逆向腺相关病毒(AAVRG)的方法来阐明表达D1和D2受体的神经元的地形组织,并将其投影到不同的纹状体和中脑子区域。我们的实验表明,AAVRG注射到D1Cre小鼠的伏隔核(NAcc)或背侧纹状体(dSTR)中分别标记了眶额内侧或前缘PFC中不同的神经元亚群。但是,在D2Cre小鼠的NAcc或dSTR中进行AAVRG注射分别标记了眶额内侧,而不标记了前缘PFC。此外,在黑质致密部(SNpc)中注射AAVRG后标记D2R +,但未标记D1R + PFC神经元。因此,我们的数据是第一个在PFC中突出独特的多巴胺受体特异性地形图谱的方法,可能对基底神经节的皮质纹状体信号产生深远的影响。在AccRG注射的D2Cre小鼠的NAcc或dSTR中分别标记了眶额内侧,而不标记了内侧前缘PFC。此外,在黑质致密部(SNpc)中注射AAVRG后标记D2R +,但未标记D1R + PFC神经元。因此,我们的数据是第一个在PFC中突出独特的多巴胺受体特定的地形图,这可能对基底神经节的皮质纹状体信号具有深远的影响。在AccRG注射的D2Cre小鼠的NAcc或dSTR中分别标记了眶额内侧,而不标记了内侧前缘PFC。此外,在黑质致密部(SNpc)中注射AAVRG后标记D2R +,但未标记D1R + PFC神经元。因此,我们的数据是第一个在PFC中突出独特的多巴胺受体特异性地形图谱的方法,可能对基底神经节的皮质纹状体信号产生深远的影响。
更新日期:2020-08-11
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