Cajal-Retzius cells and neuronal signaling in postnatal cortical networks

项目摘要 这种竞争性更新应用程序的广泛目标是揭示新的结构和功能， 海马网络，特别强调了一个相当神秘和研究不足的神经元细胞 Cajal-Retzius细胞（CR）。 研究这些细胞的重要性被文献报道所强调，这些文献报道表明， 在患有颞叶癫痫的患者亚群的海马中， 在很小的时候就经历过热性惊厥这一观察表明， 控制CR数量和功能可能参与癫痫发生过程。 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，海马CRs是第三个群体， 神经元（除锥体细胞和颗粒细胞外），在成熟的海马网络中持续存在， 完全集成在微电路中。其次，我们最近发现CRs表达多模态， 温度门控和Ca 2+渗透性通道TRPV 1。 这些发现提供了独特的机会，研究的生理和病理功能， CRs及其驱动的微电路在基因改变的动物中具有条件性增加的水平， TRPV 1表达或条件性消融囊泡谷氨酸转运蛋白。 特别地，我们将检验CRs对TRPV 1的功能性表达决定其功能的假说。 在发育中的海马密度和/或调节其突触输出。最后，我们将测试 热性惊厥范围内的温度可以影响海马CR依赖性 微电路通过TRPV 1在体外和体内。

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.