Astroglial cells in telencephalic development and plasticity

从长远来看，我的研究计划专注于了解介导大脑在整个生命周期中对其环境做出反应的能力（也称为大脑可塑性）的基本过程。总的来说，青少年比成年人更容易对“积极的”环境干预措施作出反应，如丰富生活。例如，音乐、第二语言习得和身体充实通常在青少年中比在成年人中更成功--目前的建议侧重于青少年和成年人对环境刺激的反应能力的差异。特别是，我们已经表明，幼年小鼠的环境富集导致认知改善和神经生物学变化，而这些变化在富集的成年小鼠中没有观察到。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，甚至与神经元相比，神经元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的复杂性而增加：在人脑中，星形胶质细胞与每个神经元的比例达到1.4。星形胶质细胞包括几种亚型，但它们在细胞代谢中起着关键作用，改变细胞与细胞的连接并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完整性和功能中具有明确的作用，但只有少数研究在整个发育过程中描述了这些细胞，或者检查了星形胶质细胞在整个生命周期中的功能作用。因此，我的研究计划将开始分析星形胶质细胞在整个生命周期都在正常条件下，并在响应环境富集。我们将研究星形胶质细胞的反应性和功能，从最基本的基因表达变化到整个生物体水平的功能结果。我们将采用几种尖端技术，以了解我们可以操纵星形胶质细胞功能的一般条件，星形胶质细胞功能最终将作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.