Department of Electrical Engineering, University of California, Santa Cruz, 1156 High Street, Santa Cruz, CA 95064, USA.
Department of Ophthalmology, Stanford University, Stanford, CA 94305, USA; Hansen Experimental Physics Laboratory, Stanford University, Stanford, CA 94305, USA.
Curr Biol. 2018 Jun 4;28(11):1818-1824.e2. doi: 10.1016/j.cub.2018.04.063. Epub 2018 May 24.
Proper function of the central nervous system (CNS) depends on the specificity of synaptic connections between cells of various types. Cellular and molecular mechanisms responsible for the establishment and refinement of these connections during development are the subject of an active area of research [1-6]. However, it is unknown if the adult mammalian CNS can form new type-selective synapses following neural injury or disease. Here, we assess whether selective synaptic connections can be reestablished after circuit disruption in the adult mammalian retina. The stereotyped circuitry at the first synapse in the retina, as well as the relatively short distances new neurites must travel compared to other areas of the CNS, make the retina well suited to probing for synaptic specificity during circuit reassembly. Selective connections between short-wavelength sensitive cone photoreceptors (S-cones) and S-cone bipolar cells provides the foundation of the primordial blue-yellow vision, common to all mammals [7-18]. We take advantage of the ground squirrel retina, which has a one-to-one S-cone-to-S-cone-bipolar-cell connection, to test if this connectivity can be reestablished following local photoreceptor loss [8, 19]. We find that after in vivo selective photoreceptor ablation, deafferented S-cone bipolar cells expand their dendritic trees. The new dendrites randomly explore the proper synaptic layer, bypass medium-wavelength sensitive cone photoreceptors (M-cones), and selectively synapse with S-cones. However, non-connected dendrites are not pruned back to resemble unperturbed S-cone bipolar cells. We show, for the first time, that circuit repair in the adult mammalian retina can recreate stereotypic selective wiring.
中枢神经系统（CNS）的正常功能依赖于各种类型细胞之间突触连接的特异性。在发育过程中，负责建立和完善这些连接的细胞和分子机制是一个活跃的研究领域[1-6]。然而，尚不清楚成年哺乳动物的中枢神经系统在神经损伤或疾病后是否能够形成新的、具有特定类型的突触。在这里，我们评估了在成年哺乳动物视网膜中，电路中断后是否可以重新建立特定的突触连接。视网膜中第一个突触的定型电路，以及新神经突相对于中枢神经系统其他区域必须行进的相对较短距离，使得视网膜非常适合在电路重新组装过程中探测突触的特异性。短波长敏感视锥（S- cone）和 S- cone 双极细胞之间的选择性连接为所有哺乳动物共有的原始蓝黄色视觉提供了基础[7-18]。我们利用地松鼠的视网膜，其具有 S- cone 与 S- cone 双极细胞的一对一连接，来测试在局部光感受器丧失后这种连接是否可以重建[8,19]。我们发现，在体内选择性光感受器消融后，去传入的 S- cone 双极细胞扩展了它们的树突。新的树突随机探索适当的突触层，绕过中波敏感视锥（M- cone），并与 S- cone 选择性突触连接。然而，未连接的树突不会被修剪回未受干扰的 S- cone 双极细胞的样子。我们首次表明，成年哺乳动物视网膜中的电路修复可以重新建立定型的选择性连接。
