Astroglial cells in telencephalic development and plasticity

从长远来看，我的研究计划专注于了解大脑在整个生命周期内对环境做出反应的基本过程(也称为大脑可塑性)。总体而言，青少年比成年人更容易对“积极”的环境干预措施做出反应，比如富集物。例如，音乐、第二语言习得和身体锻炼在青少年中通常比成年人更成功--目前的建议侧重于调节青少年和成年人对环境刺激做出反应的能力差异的原因。特别是，我们已经证明，环境丰富的幼鼠会导致认知改善和神经生物学变化，这在丰富的成年鼠中没有观察到。我们的研究重点是一种特定细胞的反应：星形胶质细胞，这是哺乳动物大脑中最丰富的细胞类型，即使与神经元相比，神经元也是大脑中研究最充分的细胞类型。神经元与星形胶质细胞的比例随着大脑复杂性的增加而增加：最高达到人脑内每个神经元1.4个星形胶质细胞的比例。星形胶质细胞包括几种亚型，但它们共同在细胞代谢中发挥关键作用，改变细胞间的连接，为神经元提供营养支持，此外，它们还具有神经干细胞的功能。*尽管星形胶质细胞在大脑的完整性和功能中扮演着明确的角色，但只有少数研究描绘了这些细胞在发育过程中的概况，或者研究了星形胶质细胞在整个生命周期中的功能作用。因此，我的研究计划将从分析星形胶质细胞在正常条件下和环境富集期的反应开始。我们将从最基本的基因表达变化到整个生物体水平上的功能结果来检查星形胶质细胞的响应性和功能。我们将使用几种尖端技术来了解我们可以操纵星形胶质细胞功能的一般条件，这最终将成为影响大脑活力和功能的媒介。

Over the long-term, my research program is focused on understanding the basic processes that mediate the brain's ability to respond to its environment (also known as brain plasticity) across the lifespan. On the whole, juveniles respond more readily to "positive" environmental interventions such as enrichment then adults. For example, music, second language acquisition, and physical enrichment are typically more successful in juveniles then adults- the current proposal focuses on what mediates these differences in the ability to respond to environmental stimuli between juveniles and adults. In particular, we have shown that environmental enrichment of juvenile mice leads to cognitive improvements and neurobiological changes that are not observed in enriched adults. Our research focuses on the response of a particular cell: astrocytes, which are the most abundant cell type in the mammalian brain, even as compared to neurons, the most well-studied cell type in the brain. The neuron to astrocyte ratio increases with brain complexity: culminating at 1.4 astrocytes to every neuron within the human brain. Astroglial cells encompass several subtypes, but together, they play pivotal roles in cell metabolism, modifying cell-to-cell connectivity and providing trophic support to neurons, in addition, they function as neural stem cells. ***Despite a clear role for astrocytes in brain integrity and function, only a handful of studies have profiled these cells across development, or examined the functional role of astrocytes across the lifespan. Therefore, my research program will begin by profiling astrocytes across the lifespan both under normal conditions and in response to environmental enrichment. We will examine astroglial responsivity and function from the most fundamental gene expression changes to functional outcomes at the level of the whole organism. We will employ several cutting edge techniques in order to understand the general conditions by which we can manipulate astrocyte function, which will ultimately serve as a medium through which to influence brain viability and function.**