Cajal-Retzius cells and neuronal signaling in postnatal cortical networks

描述（由申请人提供）：未成熟的大脑并不是成人大脑的一个小版本：它的回路是完全不同的，而且人们对它的理解要少得多。因此，研究神经回路如何形成是必要的，原因有几个。首先，了解正常的大脑是如何工作的是很重要的。其次，深入了解大脑异常发育如何导致神经和精神健康障碍是至关重要的。第三也是最后一点，需要一种理性的方法来为目前无法治疗的疾病创造新的治疗策略。Cajal-Retzius细胞是一种瞬时神经元，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层层压。然而，它们在突触传递介导下的快速网络/计算作用仍然相当神秘且知之甚少。基于我们已经发表的工作和在过去三年半的资助中收集的初步数据，我们建议测试一个总体假设，即发育中的海马体的Cajal-Retzius细胞是微电路的重要组成部分，在生理上，参与调节特定海马体连接的突触可塑性，但也可能有助于该区域众所周知的易受癫痫发作的影响。这个项目有直接的翻译作用

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.