Visual Experience-Dependent Expression of Fn14 Is Required for Retinogeniculate Refinement.
Visual Experience-Dependent Expression of Fn14 Is Required for Retinogeniculate Refinement.
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DOI：
10.1016/j.neuron.2018.06.036
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发表时间：
2018-08-08
期刊：
影响因子：
16.2
通讯作者：
Greenberg ME
中科院分区：
文献类型：
--
作者：
Cheadle L;Tzeng CP;Kalish BT;Harmin DA;Rivera S;Ling E;Nagy MA;Hrvatin S;Hu L;Stroud H;Burkly LC;Chen C;Greenberg ME
感官体验通过尚不清楚的分子机制影响神经连接的建立。在这里，我们采用单核 RNA 测序来研究感觉驱动的基因表达对丘脑背外侧膝状核突触细化的贡献，丘脑是处理视觉信息的大脑区域。我们发现视觉体验会诱导兴奋性丘脑皮质神经元中细胞因子受体 Fn14 的表达。通过结合电生理学和结构技术，我们证明 Fn14 对于自发活动介导的早期细化阶段是可有可无的，但 Fn14 对于后期依赖经验的发育阶段的细化至关重要。缺乏 Fn14 的小鼠的细化缺陷与功能较弱和结构较小的视黄质输入有关，表明 Fn14 介导响应感官体验的功能和解剖结构重排。这些发现将 Fn14 确定为大脑中感觉驱动基因表达和视觉敏感细化之间的分子联系。视觉体验通过诱导丘脑背外侧膝状核兴奋性神经元中细胞因子受体 Fn14 的表达，促进视网膜原路的突触细化。
Sensory experience influences the establishment of neural connectivity through molecular mechanisms that remain unclear. Here, we employ single-nucleus RNA sequencing to investigate the contribution of sensory-driven gene expression to synaptic refinement in the dorsal lateral geniculate nucleus of the thalamus, a region of the brain that processes visual information. We find that visual experience induces the expression of the cytokine receptor Fn14 in excitatory thalamocortical neurons. By combining electrophysiological and structural techniques, we show that Fn14 is dispensable for early phases of refinement mediated by spontaneous activity, but that Fn14 is essential for refinement during a later, experience-dependent period of development. Refinement deficits in mice lacking Fn14 are associated with functionally weaker and structurally smaller retinogeniculate inputs, indicating that Fn14 mediates both functional and anatomical rearrangements in response to sensory experience. These findings identify Fn14 as a molecular link between sensory-driven gene expression and vision-sensitive refinement in the brain. Visual experience promotes the synaptic refinement of the retinogeniculate circuit by inducing the expression of the cytokine receptor Fn14 in excitatory neurons of the dorsal lateral geniculate nucleus of the thalamus.
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DOI：
10.1073/pnas.1717871115
发表时间：
2018-01-30
影响因子：
11.1
作者：
Kalish BT;Cheadle L;Hrvatin S;Nagy MA;Rivera S;Crow M;Gillis J;Kirchner R;Greenberg ME
通讯作者：
Greenberg ME
影响因子：
64.8
作者：
Lin, Yingxi;Bloodgood, Brenda L.;Hauser, Jessica L.;Lapan, Ariya D.;Koon, Alex C.;Kim, Tae-Kyung;Hu, Linda S.;Malik, Athar N.;Greenberg, Michael E.
通讯作者：
Greenberg, Michael E.
影响因子：
16.2
作者：
Berry KP;Nedivi E
通讯作者：
Nedivi E
影响因子：
3.7
作者：
Gray JM;Harmin DA;Boswell SA;Cloonan N;Mullen TE;Ling JJ;Miller N;Kuersten S;Ma YC;McCarroll SA;Grimmond SM;Springer M
通讯作者：
Springer M
影响因子：
25
作者：
Hrvatin S;Hochbaum DR;Nagy MA;Cicconet M;Robertson K;Cheadle L;Zilionis R;Ratner A;Borges-Monroy R;Klein AM;Sabatini BL;Greenberg ME
通讯作者：
Greenberg ME