Analysis of molecular mechanisms for localization and functional modulation of metabotropic glutamate receptors in the central nervous system

在小脑回路中，我们研究了突触后代谢型谷氨酸受体亚型2（mGluR 2）在颗粒细胞-高尔基细胞突触的作用和突触机制，使用野生型和mGluR 2缺陷小鼠的绿色荧光蛋白阳性高尔基细胞的全细胞记录。我们发现，突触后mGluR 2因此感觉输入颗粒细胞和最有可能是重要的时空调制苔藓纤维颗粒细胞的传输之前，分配输入浦肯野celles.The纹状体在基底神经节丘脑皮质电路是一个关键的神经基板，涉及运动平衡和程序学习。黑质纹状体多巴胺能输入和纹状体内胆碱能输入对纹状体投射神经元的动态调制。然而，纹状体内乙酰胆碱（ACh）在学习行为中的作用仍有待充分阐明。在这项研究中，我们研究了纹状体内ACh在不同类型的脑梗死中的作用。 ...更多信息 通过使用免疫毒素介导的细胞靶向选择性消融纹状体胆碱能神经元来学习。我们发现，局部纹状体回路中的胆碱能调制在涉及奖励相关程序性学习和工作记忆的神经回路调节中起着关键作用。我们开发了一种新的技术，允许可逆抑制小脑网络中的胆碱能神经传递。这些转基因小鼠将作为研究小脑在运动协调和学习方面功能的动物模型。发育中的大脑皮层的第一层由两种基本的神经细胞类型组成。Cajal-Retzius（CR）细胞和非CR细胞。我们建立了转基因小鼠，其中绿色荧光蛋白（GFP）由代谢型谷氨酸受体亚型2的启动子驱动，并在皮质发育过程中在CR细胞中特异性表达。Tamalin是一种支架蛋白，包括一个95-kDa的突触后密度蛋白（PSD-95）/discs-large/ZQ-1（PDZ）结构域、一个亮氨酸拉链区和一个羧基端PDZ结合基序。Tamalin与代谢型谷氨酸受体和鸟嘌呤核苷酸交换因子细胞粘连蛋白形成复合物，并促进1组代谢型谷氨酸受体的细胞内运输和细胞表面表达。在本研究中，使用几种不同的方法，我们已经表明，Tamalin通过其不同的蛋白结合域与多种神经元蛋白相互作用。结果表明，tamalin作为一个关键因素，形成了一个蛋白质复合物与多个突触后和蛋白质运输支架蛋白。少

In the cerebellar circuit, we studied the role and synaptic mechanisms of postsynaptic metabotropic glutamate receptor subtype 2 (mGluR2) at granule cell-Golgi cell synapses, using whole-cell recording of green fluorescent protein-positive Golgi cells of wild-type and mGluR2-deficient mice. We found that postsynaptic mGluR2 thus senses inputs from granule cells and is most likely important for spatiotemporal modulation of mossy fiber-granule cell transmission before distributing inputs to Purkinje cells.The striatum in the basal ganglia-thalamocortical circuitry is a key neural substrate that is implicated in motor balance and procedural learning. The projection neurons in the striatum are dynamically modulated by nigrostriatal dopaminergic input and intrastriatal cholinergic input. The role of intrastriatal acetylcholine (ACh) in learning behaviors, however, remains to be fully clarified. In this investigation, we examine the involvement of intrastriatal ACh in different categories of … More learning by selectively ablating the striatal cholinergic neurons with use of immunotoxin-mediated cell targeting. We found that cholinergic modulation in the local striatal circuit plays a pivotal role in regulation of neural circuitry Involving reward-related procedural learning and working memory.We developed a novel technique that allowed reversible suppression of glutamatergic neurotransmission in the cerebellar network. The transgenic mice will serve as an animal model to study the cerebellar function in motor coordination and learning.Layer 1 In the developing cerebral cortex is populated by two basic neuronal cell types. Cajal-Retzius (CR) cells and non-CR cells. We generated transgenic mice in which green fluorescent protein (GFP) was driven by the promoter of metabotropic glutamate receptor subtype 2 and expressed specifically in CR cells during cortical development. The resuts imply that the layer 1 neurons dynamically change and play a distinct and integral role in the postnatal developing neocortex.Tamalin is a scaffold protein that comprises multiple protein-interacting domains, including a 95-kDa postsynaptic density protein (PSD-95)/discs-large/ZQ-1 (PDZ) domain, a leucine-zipper region, and a carboxyl-terminal PDZ binding motif. Tamalin forms a complex with metabotropic glutamate receptors and guanine nucleotide exchange factor cytohesins and promotes intracellular trafficking and cell surface expression of group 1 metabotropic glutamate receptors. In the present study, using several different approaches we have shown that tamalin interacts with multiple neuronal proteins through Its distinct protein-binding domains. The results indicate that tamalin exists as a key element that forms a protein complex with multiple postsynaptic and protein-trafficking scaffold proteins. Less