Cajal-Retzius cells and neuronal signaling in postnatal cortical networks

描述（由申请人提供）：未成熟的大脑不是成年人大脑的小型版本：其电路有着深刻的不同，并且了解得更少。因此，研究神经回路是如何形成的是必不可少的，原因有几个。首先，了解正常的大脑是如何工作的很重要。其次，深入了解异常的大脑发育如何导致神经和心理健康障碍至关重要。第三，也是最后一点，需要采取合理的方法，为目前无法治疗的疾病创造新的治疗策略。Cajal-Retzius细胞是一种短暂的神经元，在哺乳动物皮质发生过程中发挥重要作用，如控制神经元迁移和皮质分层。然而，它们的快速网络/计算角色，由突触传递介导，仍然是相当神秘和知之甚少。基于我们已经发表的工作和在过去三年半的资助期间收集的初步数据，我们建议测试总体假设，即发育中海马的Cajal-Retzius细胞是微电路的重要组成部分，该微电路在生理上参与特定海马连接的突触可塑性调节，但也可能造成该区域众所周知的易受缉获影响的情况。这个项目有一个直接的翻译 相关性，因为对成熟大脑网络功能所涉及的细胞机制的更深入理解对于为新的治疗方法提供见解至关重要， 神经发育障碍

DESCRIPTION (provided by applicant): The immature brain is not a small sized version of the adult brain: its circuits are profoundly different and much less understood. Therefore, studying how neural circuits take shape is essential for several reasons. First, it is important to understand how the normal brain works. Second, it is critical to gain insights into how abnormal brain development contributes to neurological and mental health disorders. Third and last, it is required for a rational approach to create novel therapeutic strategies for diseases that are currently untreatable. Cajal-Retzius cells are transient neurons that play important functions during mammalian corticogenesis, such as control of neuronal migration and cortical lamination. However, their fast network/computational roles, mediated by synaptic transmission, remain rather mysterious and poorly understood. Based on the work that we have already published and on the preliminary data collected during these last three and a half years of funding, we propose to test the overarching hypothesis that Cajal-Retzius cells of the developing hippocampus are an essential component of a microcircuit that is involved, physiologically, in the regulation of synaptic plasticity of specific hippocampal connections, but may also contribute to the well-known vulnerability of this region to seizures. This project has a direct translational relevance because a deeper understanding of cellular mechanisms involved in network functions of the maturing brain is critical to provide insights for novel therapeutic approaches in neurodevelopmental disorders.