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：
10369690
负责人：
Gianmaria MACCAFERRI
金额：
$ 38.97万
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 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10369690
关键词：
Address Age Animals Apoptosis Brain Cajal-Retzius cells Cell Count Cell Death Cell Density Cell Survival Cell physiology Cells Chemosensitization Development Electroencephalography Electrophysiology (science)Epilepsy Event Experimental Models Febrile Convulsions Glutamate Transporter Glutamates Hippocampus (Brain)In Vitro Inflammatory Interneurons Knock-out Laboratories Light Literature Measures Molecular Mus Neurons Output Pathologic Patients Permeability Pharmacology Physiological Physiological Processes Play Population Process Pyramidal Cells Regulation Reporting Role Signal Transduction Structure Synapses Synaptic Transmission TRPV1 gene Temperature Temporal Lobe Epilepsy Testing Transgenic Animals behavioral response cell type density design experience experimental study granule cell in vivo in vivo Model neurotransmission novel patient subsets postnatal response synaptic function

项目摘要

Project Summary The broad aim of this competitive renewal application is to shed new light on the structure and functions of the hippocampal network, with a specific emphasis on a rather mysterious and understudied neuronal cell type, the Cajal-Retzius cell (CR). The significance of studying these cells is highlighted by literature reports indicating increased densities of CRs in the hippocampus of a subpopulation of patients suffering from temporal lobe epilepsy, who also experienced febrile seizures at early ages. This observation has suggested that the physiological process controlling CR numbers and functions may be involved in the epileptogenic process. The scientific premise underlying this project relies on two main discoveries made by our laboratory. First, we have provided unequivocal evidence that hippocampal CRs are a third population of glutamatergic neurons (in addition to pyramidal and granule cells), which persist in the mature hippocampal network and are fully integrated in its microcircuits. Second, we have recently found that CRs express the polymodal, temperature-gated and Ca2+ permeable channel TRPV1. These discoveries provide unique opportunities to study the physiological and pathological functions of CRs and of the microcircuits they drive in genetically-altered animals with conditionally increased levels of TRPV1 expression or conditionally ablated vesicular glutamate transporters. In particular, we will test the hypotheses that the functional expression of TRPV1 by CRs determines their densities in the developing hippocampus and/or regulates their synaptic output. Lastly, we will test the hypothesis that temperatures in the febrile seizure range can impact hippocampal CR-dependent microcircuits via TRPV1 in vitro and in vivo.

项目摘要这种竞争性更新应用的广泛目的是为结构和功能提供新的启示海马网络，特别强调一个相当神秘且研究的神经元细胞类型，Cajal-Retzius细胞（CR）。研究这些细胞的重要性由文献报告强调，表明患有颞叶癫痫患者的亚群的海马中的CRS 早期经历了高热癫痫发作。该观察结果表明生理过程控制CR数量和功能可能与癫痫发作有关。该项目的基础科学前提取决于我们实验室的两个主要发现。第一的，我们提供了明确的证据，表明海马CR是谷氨酸能的第三个人口神经元（除了锥体和颗粒细胞外），该神经元持续存在于成熟的海马网络和完全集成在其微电路中。其次，我们最近发现CRS表达多聚峰，温度门控和Ca2+渗透通道TRPV1。这些发现提供了研究的独特机会来研究 CRS和它们在基因变化的动物中驱动的微电路，有条件地增加了 TRPV1表达或有条件烧蚀的囊泡谷氨酸转运蛋白。特别是，我们将检验以下假设，即CRS的功能表达确定它们发育中的海马和/或调节其突触输出的密度。最后，我们将测试假设高热癫痫发作范围内的温度会影响海马CR依赖性微电路通过TRPV1在体外和体内。