Development of the blue cone bipolar cell in the mouse retina

小鼠视网膜中蓝锥双极细胞的发育

• 批准号: 8339810
• 负责人: Wei Li
• 金额: $ 39.33万
• 依托单位: NATIONAL EYE INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8339810
• 关键词: Accounting; Affect; Animal Model; Biological Models; Cells; Color; Color Visions; Dendrites; Development; Face; Foundations; Length; Light; Mammals; Morphology; Mus; Neurons; Neurosciences; Opsin; Outcome; Population; Primates; Process; Retina; Retinal Cone; Signal Transduction; Specific qualifier value; Synapses; Variant; Vision; ganglion cell; interest; neuron development; postsynaptic; presynaptic; retinal neuron; synaptogenesis; transcription factor

How neuronal processes develop and establish proper wirings with their synaptic partners is one of the fundamental questions of neuroscience. The vertebrate retina is an outstanding model system for studying dendritic development and neuronal connections. One of the critical visual functions, color vision, requires precise wiring of retinal neurons. In the mouse retina, there are two types of cone photoreceptors, the short wavelength sensitive cones (S-cones), which only express S-opsin, and the long wavelength sensitive cones (M-cones), many of which co-express S-opsin. In order to generate color opponency, signals from these two types of cones have to be segregated before they are contrasted at the ganglion cell level. S-cones only account for 2-5% of the total cone population. Thus, the downstream S-cone bipolar cells (SCBCs) face the daunting task of seeking out very sparse S-cones from a majority of M-cones. The outcome is that SCBCs develop a very unique dendritic arbor with long, meager dendrites that contact a handful of S-cones. This distinctive connection between S-cones and SCBCs makes it an excellent model system to study how presynaptic neurons affect the dendritic development and synaptic targeting of postsynaptic neurons. We took advantage of an animal model (Thrb2-/- mice), where M-opsin expression is abolished and all M-cones are turned into blue cones and asked how this alteration in number and type of cone afferents will affect the dendritic development and synapse formation of SCBCs. We obtained Clm/Thrb2+/+, Clm/ Thrb2+/- and Clm/Thrb2-/- mice and compared dendritic morphology of SCBCs from these mice. We found that the number of SCBCs from Thrb2-/- mice is comparable to that in wildtype and Thrb2+/- mice. Morphologically, SCBCs from Thrb2-/- mice are indistinguishable from those in wildtype and Thrb2+/- mice in terms of length of dendrites, number of dendritic branches and number of cone contacts. Our results indicate that dendritic development of SCBCs appears to be independent of the afferent input from S-opsin expressing cones, and that true S-cones may be specified by other transcription factors than Trb2, which controls S-opsin expression.

神经元过程如何发育并与其突触伙伴建立适当的连接是神经科学的基本问题之一。脊椎动物视网膜是研究树突发育和神经元连接的杰出模型系统。 色觉是关键视觉功能之一，需要视网膜神经元的精确连接。 在小鼠视网膜中，有两种类型的视锥细胞：短波长敏感视锥细胞（S-视锥细胞），仅表达 S-视蛋白；以及长波长敏感视锥细胞（M-视锥细胞），其中许多共同表达 S-视蛋白。为了产生颜色对比，来自这两种类型视锥细胞的信号必须在神经节细胞水平上进行对比之前进行分离。 S-视锥细胞仅占视锥细胞总数的2-5%。因此，下游的 S 锥双极细胞 (SCBC) 面临着从大多数 M 锥中找出非常稀疏的 S 锥的艰巨任务。结果是，SCBC 形成了非常独特的树突乔木，其长而细小的树突与少数 S 锥体接触。 S 锥体和 SCBC 之间的这种独特联系使其成为研究突触前神经元如何影响突触后神经元的树突发育和突触靶向的优秀模型系统。 我们利用动物模型（Thrb2-/- 小鼠），其中 M-视蛋白表达被消除，所有 M-视锥细胞都变成蓝色视锥细胞，并探究视锥细胞传入数量和类型的这种变化将如何影响 SCBC 的树突发育和突触形成。 我们获得了 Clm/Thrb2+/+、Clm/Thrb2+/- 和 Clm/Thrb2-/- 小鼠，并比较了这些小鼠 SCBC 的树突形态。 我们发现 Thrb2-/- 小鼠的 SCBC 数量与野生型和 Thrb2+/- 小鼠相当。 在形态学上，来自Thrb2-/-小鼠的SCBC在树突长度、树突分支数量和视锥接触数量方面与野生型和Thrb2+/-小鼠中的SCBC没有区别。我们的结果表明，SCBC 的树突发育似乎独立于 S-视蛋白表达视锥细胞的传入输入，并且真正的 S-视锥细胞可能由控制 S-视蛋白表达的 Trb2 以外的其他转录因子指定。