Penrod Rachel D, Campagna Justin, Panneck Travis, Preese Laura, Lanier Lorene M
Department of Neuroscience, University of Minnesota Minneapolis, MN, USA ; Graduate Program in Neuroscience, University of Minnesota Minneapolis, MN, USA.
Department of Neuroscience, University of Minnesota Minneapolis, MN, USA.
Front Cell Neurosci. 2015 Jul 20;9:269. doi: 10.3389/fncel.2015.00269. eCollection 2015.
Medium spiny neurons (MSNs) are the major striatal neuron and receive synaptic input from both glutamatergic and dopaminergic afferents. These synapses are made on MSN dendritic spines, which undergo density and morphology changes in association with numerous disease and experience-dependent states. Despite wide interest in the structure and function of mature MSNs, relatively little is known about MSN development. Furthermore, most in vitro studies of MSN development have been done in simple striatal cultures that lack any type of non-autologous synaptic input, leaving open the question of how MSN development is affected by a complex environment that includes other types of neurons, glia, and accompanying secreted and cell-associated cues. Here we characterize the development of MSNs in striatal-cortical co-culture, including quantitative morphological analysis of dendritic arborization and spine development, describing progressive changes in density and morphology of developing spines. Overall, MSN growth is much more robust in the striatal-cortical co-culture compared to striatal mono-culture. Inclusion of dopamine (DA) in the co-culture further enhances MSN dendritic arborization and spine density, but the effects of DA on dendritic branching are only significant at later times in development. In contrast, exogenous Brain Derived Neurotrophic Factor (BDNF) has only a minimal effect on MSN development in the co-culture, but significantly enhances MSN dendritic arborization in striatal mono-culture. Importantly, inhibition of NMDA receptors in the co-culture significantly enhances the effect of exogenous BDNF, suggesting that the efficacy of BDNF depends on the cellular environment. Combined, these studies identify specific periods of MSN development that may be particularly sensitive to perturbation by external factors and demonstrate the importance of studying MSN development in a complex signaling environment.
中等棘状神经元（MSNs）是纹状体的主要神经元，接受来自谷氨酸能和多巴胺能传入神经的突触输入。这些突触形成于MSN树突棘上，树突棘的密度和形态会随着多种疾病以及依赖经验的状态而发生变化。尽管人们对成熟MSNs的结构和功能兴趣浓厚，但对MSN的发育了解相对较少。此外，大多数关于MSN发育的体外研究是在缺乏任何类型非自体突触输入的简单纹状体培养物中进行的，这使得MSN发育如何受到包括其他类型神经元、神经胶质细胞以及伴随的分泌和细胞相关信号在内的复杂环境影响这一问题悬而未决。在这里，我们描述了纹状体 - 皮质共培养中MSNs的发育情况，包括对树突分支和棘突发育的定量形态分析，描述了发育中棘突密度和形态的渐进变化。总体而言，与纹状体单培养相比，MSN在纹状体 - 皮质共培养中的生长更为强劲。在共培养中加入多巴胺（DA）进一步增强了MSN的树突分支和棘突密度，但DA对树突分支的影响仅在发育后期才显著。相比之下，外源性脑源性神经营养因子（BDNF）对共培养中MSN的发育影响极小，但在纹状体单培养中显著增强了MSN的树突分支。重要的是，共培养中抑制NMDA受体可显著增强外源性BDNF的作用，这表明BDNF的功效取决于细胞环境。综合这些研究确定了MSN发育的特定时期，这些时期可能对外部因素的干扰特别敏感，并证明了在复杂信号环境中研究MSN发育的重要性。
