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Cajal-Retzius cells and neuronal signaling in postnatal cortical networks

出生后皮质网络中的 Cajal-Retzius 细胞和神经元信号传导

基本信息

批准号：
8697567
负责人：
Gianmaria MACCAFERRI
金额：
$ 40.28万
依托单位：
NORTHWESTERN UNIVERSITY AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-01-15 至 2019-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8697567
关键词：
Adult Architecture Brain Cajal-Retzius cells Coupled Data Development Disease Electrophysiology (science)Elements Epilepsy Febrile Convulsions Feedback Funding Glutamate Receptor Glutamates Hippocampal Formation Hippocampus (Brain)In Vitro Interneurons Knowledge Laboratories Mediating Memory Mental disorders N-Methylaspartate Nature Neurodevelopmental Disorder Neurologic Neurons Neurotransmitters Output Pathologic Processes Pathway interactions Physiological Play Population Heterogeneity Property Publishing Pyramidal Cells Regulation Role Seizures Sensory Shapes Side Signal Transduction Synapses Synaptic Transmission Synaptic plasticity Techniques Testing Work base career cell type entorhinal cortex granule cell in vivo in vivo Model insight juvenile animal migration nervous system disorder neural circuit neuron development neurotransmitter release novel novel therapeutic intervention novel therapeutics optogenetics postnatal postsynaptic prevent public health relevance research study transmission process

项目摘要

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.

描述(申请人提供)：未成熟的大脑不是成人大脑的一个小版本：它的电路截然不同，而且人们对它的了解要少得多。因此，出于几个原因，研究神经回路是如何形成的是至关重要的。首先，了解正常大脑是如何工作的是很重要的。其次，了解大脑发育异常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，需要一种理性的方法来为目前无法治愈的疾病创造新的治疗策略。Cajal-Retzius细胞是一种暂时性神经元，在哺乳动物的皮质发生过程中发挥着重要的功能，如控制神经元的迁移和皮质的分层。然而，它们由突触传递介导的快速网络/计算作用仍然相当神秘和鲜为人知。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，我们建议测试压倒一切的假设，即发育中的海马区的Cajal-Retzius细胞是微电路的重要组成部分，从生理上讲，微电路参与调节特定海马区连接的突触可塑性，但也可能有助于众所周知的该区域对癫痫发作的脆弱性。这个项目有一个直接的翻译相关性是因为更深入地了解成熟大脑的网络功能所涉及的细胞机制对于提供新的治疗方法是至关重要的神经发育障碍。