Thalamic Contributions to the developing EEG

项目摘要/摘要 尽管新生儿脑电(EEG)已有65年以上的历史，但我们对脑电节律的理解 与正常发育和脑损伤相关的皮质活动模式在很大程度上仍然是推测的。这个 目前项目的长期目标是创建一个发展活动图谱，其中有令人震惊的脑电模式 在高危新生儿中，与特定脑区和神经元类型的破坏相匹配。第一步 为了实现这一目标，需要一种非麻醉的临床前模型，并证明其与胎儿和 细胞可通过基因操纵的新生儿大脑皮质活动及其潜在影响 严格探测了大脑皮层回路。通过测量皮层深度和相应的活体活动 丘脑网络在发育中的新生啮齿动物，我们将提供洞察电路的变化，可能 为人类胎儿丘脑皮质发育提供信息，为未来婴儿和 非人灵长类动物。通过控制丘脑神经元的活动，我们将分析不同的贡献 丘脑的中继性和抑制性神经元对脑电特定特征成熟的共同作用 发育中的人类和啮齿动物。考虑到脆弱的高危新生儿在成像和诊断方面的挑战， EEG有可能成为一种有价值且廉价的床边诊断工具。更好的理解 对皮质活动发育的控制将有助于新生儿脑损伤后的诊断和改善 针对经常导致的认知和智力残疾的治疗。

Project Summary/Abstract Despite over 65 years of electroencephalography (EEG) in newborn infants, our understanding of the rhythmic cortical activity patterns associated with normal development and brain injury remains largely speculative. The long term goal of the current project is to create a developmental activity atlas in which abberant EEG patterns in the at-risk newborn are matched to specific disruptions in brain areas and neuronal types. A first step towards this goal requires an un-anesthetized preclinical model with demonstrated homology to fetal and neonatal human cortical activity in which cells can be genetically manipulated and the underlying effects on cortical circuits rigorously probed. By measuring activity in vivo through the depth of cortex and corresponding thalamic networks in developing neonatal rodents, we will provide insight into the circuit changes that may underlie human fetal thalamo-cortical development to inform future studies of subcortical injury in infants and non-human primates. By manipulating the activity of thalamic neurons we will assay the distinct contributions of the thalamic relay and inhibitory neurons to the maturation of specific features of the EEG common to developing humans and rodents. Given the challenges of imaging and diagnosis in the fragile at-risk newborn, EEG has the potential to be a valuable and inexpensive bedside diagnostic tool. An improved understanding of the control of cortical activity development will inform diagnosis after neonatal brain injury and improve targeting of treatments for the cognitive and intellectual disability that often results.