Department of Molecular and Cellular Biology and Center for Brain Science, Harvard University, Cambridge, MA 02138, USA; Departments of Ophthalmology and Physiology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94143, USA.
Department of Molecular and Cellular Biology and Center for Brain Science, Harvard University, Cambridge, MA 02138, USA.
Neuron. 2018 Sep 19;99(6):1145-1154.e6. doi: 10.1016/j.neuron.2018.08.019. Epub 2018 Sep 6.
Distinct neuronal types connect in complex ways to generate functional neural circuits. The molecular diversity required to specify this connectivity could be supplied by multigene families of synaptic recognition molecules, but most studies to date have assessed just one or a few members at a time. Here, we analyze roles of cadherins (Cdhs) in formation of retinal circuits comprising eight neuronal types that inform the brain about motion in four directions. We show that at least 15 classical Cdhs are expressed by neurons in these circuits and at least 6 (Cdh6-10 and 18) act individually or in combinations to promote specific connectivity among the cells. They act in part by directing the processes of output neurons and excitatory interneurons to a cellular scaffold formed by inhibitory interneurons. Because Cdhs are expressed combinatorially by many central neurons, similar interactions could be involved in patterning circuits throughout the brain.
不同类型的神经元以复杂的方式连接，从而形成功能性的神经回路。为了指定这种连接的分子多样性，可以由突触识别分子的多基因家族提供，但迄今为止的大多数研究一次只评估一个或几个成员。在这里，我们分析钙黏蛋白（Cdhs）在包括八个神经元类型的视网膜回路形成中的作用，这些神经元类型向大脑提供关于四个方向运动的信息。我们表明，这些回路中的神经元至少表达 15 种经典的钙黏蛋白，并且至少 6 种（Cdh6-10 和 18）单独或组合作用以促进细胞之间的特异性连接。它们的作用部分是通过将输出神经元和兴奋性中间神经元的过程引导到由抑制性中间神经元形成的细胞支架上。由于许多中枢神经元以组合的方式表达钙黏蛋白，因此类似的相互作用可能涉及整个大脑中回路的模式形成。
