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Dendritogenesis of neocortical pyramidal cells and interneurons: regulation by AMPA and NMDA receptors.

新皮质锥体细胞和中间神经元的树突发生：AMPA 和 NMDA 受体的调节。

基本信息

批准号：
225123516
负责人：
Professorin Dr. Petra Wahle
金额：
--
依托单位：
Lehrstuhl für Biochemie I - Rezeptorbiochemie
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2012
资助国家：
德国
起止时间：
2011-12-31 至 2015-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/225123516?language=en
关键词：
Dendritogenesis neocortical pyramidal cells interneurons

项目摘要

All cortical neurons express ionotropic glutamate receptors. They are essential determinants of synaptic transmission and adult function, and important regulators of early postnatal differentiation. With an overexpression strategy, we demonstrated a contribution of specific biophysically distinct AMPA receptor isoforms for dendritic growth and spine formation of pyramidal neurons and multipolar interneurons. Furthermore, we showed that the AMPA receptor-induced dendritic growth requires NMDA receptors and L-type calcium channels. We are now focussing on two aims. First, we propose to analyze the effects of an enhancement of endogenous AMPA receptor function by using 1. an overexpression of transmembrane AMPA receptor regulatory proteins, TARPs, and 2. Ampakines as positive allosteric modulators. Little is known on the function about the various TARP isoforms in neocortical neurons, and they have not been analysed in the context of development and morphological differentiation. Second, we propose to characterize the role of NMDA receptor isoforms for dendritic growth, in particular of cortical interneurons. Knowledge of the role of NMDA receptors in interneurons is surprisingly limited. The project will deliver novel insights into the function of type I and type II TARPS in the two cortical neuron classes, and unravel the role of NMDA receptors, in particular for interneuronal differentiation.

所有皮质神经元表达离子型谷氨酸受体。它们是突触传递和成年功能的基本决定因素，也是出生后早期分化的重要调节因子。通过过表达策略，我们证明了特定的生物药理学上不同的AMPA受体亚型对锥体神经元和多极中间神经元的树突生长和棘形成的贡献。此外，我们发现AMPA受体诱导的树突生长需要NMDA受体和L-型钙通道。我们现在集中在两个目标上。首先，我们建议使用1分析内源性AMPA受体功能增强的影响。跨膜AMPA受体调节蛋白，TARP的过表达，和2.作为正向变构调节剂的安帕金。关于各种TARP亚型在新皮层神经元中的功能知之甚少，并且尚未在发育和形态分化的背景下对其进行分析。第二，我们建议的特点的作用，NMDA受体亚型的树突状细胞的生长，特别是皮质中间神经元。NMDA受体在中间神经元中的作用的知识是令人惊讶的有限。该项目将提供新的见解I型和II型TARPS在两个皮层神经元类的功能，并解开NMDA受体的作用，特别是神经元间的分化。