Nicotinic regulation of local and long-range input balance drives top-down attentional circuit maturation

被引：18

作者：

Falk, Elisa N. ^{[1
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Norman, Kevin J. ^{[1
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Garkun, Yury ^{[1
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]}

Demars, Michael P. ^{[1
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Im, Susanna ^{[1
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Taccheri, Giulia ^{[1
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Short, Jenna ^{[1
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Caro, Keaven ^{[1
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McCraney, Sarah E. ^{[1
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Cho, Christina ^{[1
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]}

Smith, Milo R. ^{[1
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Lin, Hung-Mo ^{[6
]}

Koike, Hiroyuki ^{[1
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]}

Bateh, Julia ^{[1
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Maccario, Priscilla ^{[1
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Waltrip, Leah ^{[1
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Janis, Meaghan ^{[1
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Morishita, Hirofumi ^{[1
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]}

机构：

[1] Icahn Sch Med Mt Sinai, Dept Psychiat, One Gustave L Levy Pl, New York, NY 10029 USA

[2] Icahn Sch Med Mt Sinai, Nash Family Dept Neurosci, One Gustave L Levy Pl, New York, NY 10029 USA

[3] Icahn Sch Med Mt Sinai, Dept Ophthalmol, One Gustave L Levy Pl, New York, NY 10029 USA

[4] Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, One Gustave L Levy Pl, New York, NY 10029 USA

[5] Icahn Sch Med Mt Sinai, Friedman Brain Inst, One Gustave L Levy Pl, New York, NY 10029 USA

[6] Icahn Sch Med Mt Sinai, Dept Populat Hlth Sci & Policy, One Gustave L Levy Pl, New York, NY 10029 USA

来源：

SCIENCE ADVANCES | 2021年 / 7卷 / 10期

关键词：

FRAGILE-X-SYNDROME; ACETYLCHOLINE-RECEPTORS; BETA-2; SUBUNITS; MOUSE MODEL; CORTEX; NEURONS; FMRP; DYSFUNCTION; PLASTICITY; LYNX1;

D O I：

10.1126/sciadv.abe1527

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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, Lynxl. Lynxl 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 Lynxl in top-down projections. Nicotinic signaling may serve as a target to rebalance local/long-range balance and treat cognitive deficits in neurodevelopmental disorders.

引用

页数：16

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