Yetnikoff Leora, Reichard Rhett A, Schwartz Zachary M, Parsely Kenneth P, Zahm Daniel S
Department of Pharmacological and Physiological Science, St. Louis University School of Medicine, St. Louis, Missouri, 63104.
J Comp Neurol. 2014 Apr 1;522(5):1031-47. doi: 10.1002/cne.23459.
The mesocorticolimbic dopamine system has long attracted the interest of researchers concerned with the unique gamut of behavioral and mental health vulnerabilities associated with adolescence. Accordingly, the development of the mesocorticolimbic system has been studied extensively, but almost exclusively with regard to dopaminergic output, particularly in the nucleus accumbens and medial prefrontal cortex. To the contrary, the ontogeny of inputs to the ventral tegmental area (VTA), the source of mesocorticolimbic dopamine, has been neglected. This is not a trivial oversight, as the activity of VTA neurons, which reflects their capacity to transmit information about salient events, is sensitively modulated by inputs. Here, we assessed the development of VTA afferent connections using the β subunit of cholera toxin (Ctβ) as a retrograde axonal tracer in adolescent (postnatal day 39) and early adult (8-9-week-old) rats. After intra-VTA injections of Ctβ, adolescent and early adult animals exhibited qualitatively similar distributions of retrogradely labeled neurons in the sense that VTA-projecting neurons were present at all of the same rostrocaudal levels in all of the same structures in both age groups. However, quantitation of retrogradely labeled neurons revealed that adolescent brains, compared with early adult brains, had significantly fewer VTA-projecting neurons preferentially within an interconnected network of cortical and striatopallidal forebrain structures. These findings provide a novel perspective on the development of the mesocorticolimbic dopamine system and may have important implications for age-dependent specificity in the function of this system, particularly with regard to adolescent impulsivity and mental health vulnerabilities.
中脑边缘多巴胺系统长期以来一直吸引着研究人员的兴趣，这些研究人员关注与青春期相关的一系列独特的行为和心理健康易损性。因此，中脑边缘系统的发育已得到广泛研究，但几乎完全集中在多巴胺能输出方面，特别是在伏隔核和内侧前额叶皮质。相反，中脑边缘多巴胺的来源——腹侧被盖区（VTA）的输入的个体发生却被忽视了。这并非一个微不足道的疏忽，因为VTA神经元的活动反映了它们传递有关显著事件信息的能力，而这种活动会受到输入的敏感调节。在这里，我们使用霍乱毒素β亚基（Ctβ）作为逆行轴突示踪剂，评估了青春期（出生后第39天）和成年早期（8 - 9周龄）大鼠中VTA传入连接的发育情况。在向VTA内注射Ctβ后，青春期和成年早期动物在逆行标记神经元的分布上表现出定性相似性，即两个年龄组中，在所有相同结构的相同头尾水平上都存在投射到VTA的神经元。然而，对逆行标记神经元的定量分析显示，与成年早期大脑相比，青春期大脑中优先在皮质和纹状体苍白球前脑结构的相互连接网络内投射到VTA的神经元明显更少。这些发现为中脑边缘多巴胺系统的发育提供了一个新的视角，并且可能对该系统功能的年龄依赖性特异性具有重要意义，特别是在青少年冲动性和心理健康易损性方面。
