White mater neurons & nitric oxide in neonatal neocortex

人类大脑的实质性发育，特别是大脑皮层的突触重组，发生在出生后。在出生后早期，正常的皮质发育容易受到破坏。病因包括原发性损伤（癫痫、感染、损伤）、早期围产期损伤的延迟效应（缺氧/缺血、胎儿酒精暴露、感染，如艾滋病）和遗传相关疾病（唐氏综合征、苯丙酮尿症、脆性X染色体）。这些过程会导致智力迟钝，并与异常的皮层突触结构有关。首先了解介导皮层突触发育和完善的细胞和分子机制是必不可少的。皮层中介导的突触传递是一个特别关键的过程，因为这些突触对早期经历的结构和功能修饰敏感，会导致过度激活的神经毒性皮质白色物质（WM）神经元发育特别早，并且它们可能导致过度激活的神经毒性。皮质白色物质（WM）神经元发育特别早，并在建立最初的突触能突触联系中发挥重要作用。直到最近，人们还认为在正常发育过程中，这些WM神经元中的大多数都会死亡。然而，我们现在知道，在整个发育过程中，有相当一部分存活下来并支配覆盖的皮层。此外，许多神经元表达用于合成一氧化氮（NO）的酶，所述一氧化氮（NO）与谷氨酸释放、神经发育、突触可塑性和神经变性有关。然而，我们对这些存活的WM神经元的功能特性或突触相互作用以及NO在发育过程中调节谷氨酸能突触的作用知之甚少。因此，我们建议阐明的功能特性，神经支配模式，WOM神经元的突触相互作用，以及他们的能力门的新生儿皮层上的突触的吞吐量。我们还将阐明NO产生和调节谷氨酸的信号通路的发育调节。

Substantial human brain development, particularly synaptic reorganization of the cerebral cortex, occurs postnatally. During the early postnatal period, normal cortical development is susceptible to disruption. Causes include primary insults (seizures, infection, injury), delayed effects of earlier perinatal damage (hypoxia/ischemia, fetal alcohol exposure, infections, e.g. AIDS), and genetically linked diseases (Down's syndrome, PKU, fragile X). These processes can lead to mental retardation and are associated with abnormal cortical synaptic architecture Thus, a first understanding of the cellular and molecular mechanisms that mediate development and refinement of cortical synapses is essential The development and modifiability of glutamate-mediated synaptic transmission in the cortex is a particularly critical process as these synapses are sensitive to structural and functional modification by early experience and they can contribute to neurotoxicity from over-activation. Cortical white matter (WM) neurons develop particularly early and they can contribute to neurotoxicity from over-activation. Cortical white matter (WM) neurons develop particularly early and play an important role in establishment of initial glutamatergic synaptic linkages. Until recently, it was assumed that during normal development, most of these WM neurons die. However, we now know that a substantial portion survives and innervates the overlying cortex throughout development. Moreover, many of the neurons express the enzyme for synthesizing nitric oxide (NO) which has been implicated in glutamate release, neurodevelopment, synaptic plasticity, and neurodegeneration. However, we know little about the functional properties or synaptic interactions of these surviving WM neurons or the role of NO in modulating glutamatergic synapses during development. Thus, we propose to elucidate the functional properties, the innervation pattern, the synaptic interactions of WOM neurons, and their ability to gate the throughput of glutamatergic synapses in the overlying neonatal cortex. We will also elucidate the developmental regulation of the signaling pathway where NO is produced and acts to modulate glutamate.