Blocking PirB up-regulates spines and functional synapses to unlock visual cortical plasticity and facilitate recovery from amblyopia.
Blocking PirB up-regulates spines and functional synapses to unlock visual cortical plasticity and facilitate recovery from amblyopia.
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DOI：
10.1126/scitranslmed.3010157
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发表时间：
2014-10-15
影响因子：
17.1
通讯作者：
Shatz CJ
中科院分区：
文献类型：
--
作者：
Bochner DN;Sapp RW;Adelson JD;Zhang S;Lee H;Djurisic M;Syken J;Dan Y;Shatz CJ
在发育的关键时期，大脑很容易因环境刺激而发生变化，但这种神经可塑性到成年后就会下降。通过在特定年龄急剧破坏配对免疫球蛋白样受体 B (PirB) 功能，我们发现 PirB 在整个生命过程中积极抑制神经可塑性。我们通过将条件性 PirB 等位基因基因引入小鼠体内或通过微型泵将可溶性 PirB 胞外域 (sPirB) 注入小鼠视觉皮层来破坏 PirB 功能。我们发现，神经可塑性（通过剥夺小鼠一只眼睛的视力并测试眼优势来测量）在关键期和成年期 PirB 功能被破坏时，这种治疗都增强了神经可塑性。急性 PirB 阻断引发了新的功能性突触的形成，第 5 层锥体神经元树突上的微型兴奋性突触后电流 (mEPSC) 频率和棘密度增加表明了这一点。此外，在剥夺期后输注 sPirB 1 周后，弱视（因长期单眼剥夺导致视力和脊柱密度下降）有可能恢复。因此，成人视觉皮层的神经可塑性受到主动抑制，并且可以通过阻断 PirB 功能来增强。
During critical periods of development, the brain easily changes in response to environmental stimuli, but this neural plasticity declines by adulthood. By acutely disrupting paired immunoglobulin-like receptor B(PirB) function at specific ages, we show that PirB actively represses neural plasticity throughout life. We disrupted PirB function either by genetically introducing a conditional PirB allele into mice or by minipump infusion of a soluble PirB ectodomain (sPirB) into mouse visual cortex. We found that neural plasticity, as measured by depriving mice of vision in one eye and testing ocular dominance, was enhanced by this treatment both during the critical period and when PirB function was disrupted in adulthood. Acute blockade of PirB triggered the formation of new functional synapses, as indicated by increases in miniature excitatory postsynaptic current (mEPSC) frequency and spine density on dendrites of layer 5 pyramidal neurons. In addition, recovery from amblyopia— the decline in visual acuity and spine density resulting from long-term monocular deprivation— was possible after a 1-week infusion of sPirB after the deprivation period. Thus, neural plasticity in adult visual cortex is actively repressed and can be enhanced by blocking PirB function.
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影响因子：
16.2
作者：
Chowdhury, Shoaib;Shepherd, Jason D.;Worley, Paul F.
通讯作者：
Worley, Paul F.
影响因子：
5.5
作者：
HUBEL, DH;WIESEL, TN
通讯作者：
WIESEL, TN
影响因子：
25
作者：
Madisen L;Zwingman TA;Sunkin SM;Oh SW;Zariwala HA;Gu H;Ng LL;Palmiter RD;Hawrylycz MJ;Jones AR;Lein ES;Zeng H
通讯作者：
Zeng H
影响因子：
16.2
作者：
Datwani, Akash;McConnell, Michael J.;Kanold, Patrick O.;Micheva, Kristina D.;Busse, Brad;Shamloo, Mehrdad;Smith, Stephen J.;Shatz, Carla J.
通讯作者：
Shatz, Carla J.
影响因子：
5.3
作者：
Kang, Erin;Durand, Severine;Fagiolini, Michela
通讯作者：
Fagiolini, Michela