A new approach to estimate the number, density and variability of receptors at central synapses
A new approach to estimate the number, density and variability of receptors at central synapses
复制标题
一种估计中央突触受体数量、密度和变异性的新方法
DOI：
--
复制
发表时间：
1999
影响因子：
3.4
通讯作者：
Z. Nusser
中科院分区：
文献类型：
--
作者：
Z. Nusser
神经元网络中的信息处理受到神经细胞之间突触连接特性的影响。影响突触连接行为和动力学的因素包括两个细胞之间释放部位的数量、每个部位释放递质的概率以及每个部位产生的突触后反应的大小。这些参数传统上是通过量化分析来估计的，这是一种开发并成功应用于神经肌肉接头的方法(del Castillo&Katz，1954)。微型端板电位具有高斯分布，其平均值等于诱发响应的量子大小。然而，在大多数中枢神经系统(CNS)神经细胞中，微小的兴奋性和抑制性突触后电流(mEPSCs和mIPSCs)的幅度分布不是高斯的，而是偏向较大的值，这使得量子分析的解释变得复杂(Jack等人，1994；Walmsley，1995)。此外，突触后反应的大小和递质释放概率在不同部位之间可能并不一致(Edwards等人，1990；Korn&Faber，1991；Jack等人，1994；Dobrunz&Stevens，1997；Markram等人，1998)，这使得太多的未知变量无法仅通过量化分析来确定。通过形态分析和电生理分析相结合，可以减少未知参数的数量。例如，几项研究(Kornet等人，1982；Gulyaset等人，1993；Buhlet等人，1997)已成功地应用超微结构分析来确定两个同时记录的神经元之间的释放部位的数量。此外，定量电子显微镜放射自显影已被应用于估计神经肌肉接头处突触后烟碱型乙酰胆碱受体的数量和密度(Salpeter&Loring，1985年)，然而，这种方法还没有成功地应用于中枢、γ-氨基丁酸或谷氨酸能突触。我们发展了另一种解剖学和电生理学相结合的方法，通过测定突触后GABA和谷氨酸受体的数量、密度和变异性来估计突触后反应的大小(Nusser等人，1997,1998a，b)。这种方法是基于对突触群体中具有特定抗体的突触后受体的电子显微镜免疫金定位(Triller等人，1985；Somogyi等人，1990；Baude等人，1993；Phendet等人，1995；Matsubara等人，1996)，并使用Patch-Gate对存在于同一突触群体中的功能性受体的数量进行电生理学估计。
Information processing within a neuronal network is influenced by the properties of synaptic connections between nerve cells. Factors that influence the behaviour of synaptic connections and the dynamics include the number of release sites between two cells, the probability of transmitter release at each site and the size of the postsynaptic response generated at each site. These parameters have traditionally been estimated with quantal analysis, a method developed and successfully applied at the neuromuscular junction (del Castillo & Katz, 1954). Miniature end-plate potentials have a Gaussian distribution with a mean value equal to the quantal size of the evoked responses. However, in most nerve cells of the central nervous system (CNS), the amplitude distributions of miniature excitatory and inhibitory postsynaptic currents (mEPSCs and mIPSCs, respectively) are not Gaussian, but are skewed towards larger values, which complicates the interpretation of quantal analysis (Jack et al., 1994; Walmsley, 1995). Furthermore, the size of postsynaptic responses and the transmitter release probability may not be uniform between different sites (Edwards et al., 1990; Korn & Faber, 1991; Jack et al., 1994; Dobrunz & Stevens, 1997; Markram et al., 1998), leaving too many unknown variables to be determined by quantal analysis alone. By combining morphological and electrophysiological analysis, the number of unknown parameters can be reduced. For example, several studies (Kornet al., 1982; Gulyaset al., 1993; Buhlet al., 1997) have successfully applied ultrastructural analysis to determine the number of release sites between two simultaneously recorded neurons. Furthermore, quantitative, electron microscopic autoradiography has been applied to estimate the number and density of postsynaptic nicotinic acetylcholine receptors at neuromuscular junctions (reviewed by Salpeter & Loring, 1985), however, this method has not been applied successfully at central, γ-aminobutyric acid (GABA)or glutamatergic synapses. We have developed another combined anatomical and electrophysiological approach to estimate the size of postsynaptic responses by determining the number, density and variability of postsynaptic GABA and glutamate receptors (Nusser et al., 1997, 1998a, b). This method is based on electron microscopic immunogold localization of postsynaptic receptors with specific antibodies in a population of synapses (Triller et al., 1985; Somogyi et al., 1990; Baude t al., 1993; Phendet al., 1995; Matsubara et al., 1996), and electrophysiological estimation of the number of functional receptors present at the same population of synapses using patch-
DOI：
10.1073/pnas.91.16.7698
发表时间：
1994-08-02
影响因子：
11.1
作者：
OTIS, TS;DE KONINCK, Y;MODY, I
通讯作者：
MODY, I