Nicotinic regulation of local and long-range input balance drives top-down attentional circuit maturation.
Nicotinic regulation of local and long-range input balance drives top-down attentional circuit maturation.
复制标题
尼古丁对局部和远程输入平衡的调节驱动自上而下的注意回路成熟。
DOI：
10.1126/sciadv.abe1527
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发表时间：
2021-03
期刊：
影响因子：
13.6
通讯作者：
Morishita H
中科院分区：
文献类型：
--
作者：
Falk EN;Norman KJ;Garkun Y;Demars MP;Im S;Taccheri G;Short J;Caro K;McCraney SE;Cho C;Smith MR;Lin HM;Koike H;Bateh J;Maccario P;Waltrip L;Janis M;Morishita H
在脆性X综合征小鼠模型中，尼古丁信号调节自上而下的神经回路成熟并恢复注意缺陷。认知功能取决于额叶皮质的发育；然而，驱动这一过程的机制却知之甚少。在这里，我们发现尼古丁胆碱能系统的动态调节是与自上而下的额叶神经元投射到视觉皮层相关的注意回路成熟的关键驱动因素。自上而下的神经元接受强大的胆碱能输入，但它们的尼古丁张力在青春期后通过增加尼古丁刹车Lynx1的表达而降低。Lynx1在青春期后将局部和远程输入之间的平衡转移到自上而下的额叶神经元，并促进成年期注意力行为的建立。在脆性X综合征的小鼠模型中，这一关键的成熟过程被破坏，但通过在自上而下的投射中引入Lynx1来抑制尼古丁音调，从而得以挽救。尼古丁信号可能作为一个靶点，以重新平衡局部/远程平衡和治疗神经发育障碍的认知缺陷。
Nicotinic signaling regulates top-down circuit maturation and restores attention deficits in mouse model of fragile X syndrome. Cognitive function depends on frontal cortex development; however, the mechanisms driving this process are poorly understood. Here, we identify that dynamic regulation of the nicotinic cholinergic system is a key driver of attentional circuit maturation associated with top-down frontal neurons projecting to visual cortex. The top-down neurons receive robust cholinergic inputs, but their nicotinic tone decreases following adolescence by increasing expression of a nicotinic brake, Lynx1. Lynx1 shifts a balance between local and long-range inputs onto top-down frontal neurons following adolescence and promotes the establishment of attentional behavior in adulthood. This key maturational process is disrupted in a mouse model of fragile X syndrome but was rescued by a suppression of nicotinic tone through the introduction of Lynx1 in top-down projections. Nicotinic signaling may serve as a target to rebalance local/long-range balance and treat cognitive deficits in neurodevelopmental disorders.
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