Moss B L, Role L W
Department of Anatomy and Cell Biology, Columbia University College of Physicians and Surgeons, New York, New York 10032.
J Neurosci. 1993 Jan;13(1):13-28. doi: 10.1523/JNEUROSCI.13-01-00013.1993.
Although presynaptic input can influence the number and distribution of ACh receptors (AChRs) on muscle, the role of cellular interactions in the development of transmitter sensitivity in neurons is less clear. To determine whether presynaptic input modifies neuronal AChR channel function and distribution, we must first ascertain the profile of changes in receptor properties relative to the timing of synapse formation. We have examined the temporal aspects of synaptogenesis in the lumbar sympathetic ganglia of the embryonic chick in anatomical experiments with anterograde 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate labeling of presynaptic inputs and cytochrome oxidase histochemistry. Biophysical studies of sympathetic neurons, within hours of removal from animals at different stages relative to synapse formation, show that both the properties and distribution of AChR channels are modified concurrent with a significant increase in presynaptic input to the neurons. The most striking change in AChR channel distribution is revealed by patching multiple sites on the surface of individual neurons. Following innervation in vivo, many neurons express only one of the four AChR channel subtypes and the AChRs are clustered in discrete, high-activity patches. Furthermore, when neurons at this stage express more than one AChR channel subtype, the different classes are often spatially segregated from one another on the cell surface. This contrasts with patches from neurons removed earlier on, which have lower overall activity, often comprised of multiple channel subtypes. Comparison of the AChR properties of acutely dispersed neurons to those of neurons maintained in vitro indicates that most features of AChR channels are conserved despite their removal from presynaptic and other in vivo influences. These findings are consistent with inductive interactions between pre- and postsynaptic neurons playing an important regulatory role in transmitter receptor expression.
虽然突触前输入可以影响肌肉上乙酰胆碱受体（AChRs）的数量和分布，但细胞间相互作用在神经元递质敏感性发育中的作用尚不清楚。为了确定突触前输入是否会改变神经元AChR通道的功能和分布，我们必须首先确定受体特性相对于突触形成时间的变化情况。我们通过用1,1'-二辛基-3,3,3',3'-四甲基吲哚羰花青高氯酸盐对突触前输入进行顺行标记以及细胞色素氧化酶组织化学，对胚胎鸡腰交感神经节突触发生的时间方面进行了解剖学实验研究。对处于相对于突触形成的不同阶段的动物进行取材后数小时内，对交感神经元进行生物物理研究，结果表明，AChR通道的特性和分布在与神经元突触前输入显著增加的同时发生了改变。通过对单个神经元表面的多个位点进行膜片钳记录，揭示了AChR通道分布最显著的变化。在体内神经支配后，许多神经元仅表达四种AChR通道亚型中的一种，且AChRs聚集在离散的高活性斑块中。此外，当处于这个阶段的神经元表达不止一种AChR通道亚型时，不同类型的通道在细胞表面通常在空间上相互分离。这与早期取材的神经元的斑块形成对比，早期取材的神经元整体活性较低，通常由多种通道亚型组成。将急性分散的神经元的AChR特性与体外培养的神经元的AChR特性进行比较表明，尽管AChR通道已脱离突触前和其他体内影响，但大多数特性得以保留。这些发现与突触前和突触后神经元之间的诱导性相互作用在递质受体表达中发挥重要调节作用是一致 的。
