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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：
9912203
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/9912203
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 Structure of molecular layer of cerebellar cortex 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.

项目摘要这项竞争性续签申请的广泛目的是为了解海马网，特别强调一个相当神秘和未被充分研究的神经细胞类型：Cajal-Retzius细胞(CR)。研究这些细胞的重要性被文献报道所强调，这些报告表明细胞密度增加。颞叶癫痫患者亚群的海马区CRS，他们也在很小的时候就经历了发热性癫痫。这一观察表明，生理过程控制CR的数量和功能可能参与癫痫的形成过程。这个项目的科学前提依赖于我们实验室的两个主要发现。第一, 我们已经提供了明确的证据表明，海马区CRS是谷氨酸能的第三个种群。神经元(除锥体细胞和颗粒细胞外)，它们持续存在于成熟的海马网和完全集成在它的微电路中。第二，我们最近发现CRS表达多态，温度门控和钙离子渗透通道TRPV1。这些发现为研究血管紧张素转换酶的生理和病理功能提供了独特的机会。 CRS及其驱动的微电路在转基因动物中的水平有条件地增加 TRPV1的表达或条件消融的囊泡谷氨酸转运体。特别是，我们将测试CRS对TRPV1的功能表达决定其在发育中的海马区的密度和/或调节它们的突触输出。最后，我们将测试高热惊厥范围内的温度可影响海马CR依赖的假说在体外和体内通过TRPV1的微电路。