Neuregulin-Dependent Regulation of Fast-Spiking Interneuron Excitability Controls the Timing of the Critical Period
Neuregulin-Dependent Regulation of Fast-Spiking Interneuron Excitability Controls the Timing of the Critical Period
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DOI：
10.1523/jneurosci.4242-15.2016
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发表时间：
2016-10-05
影响因子：
5.3
通讯作者：
Quinlan, Elizabeth M.
中科院分区：
文献类型：
--
作者：
Gu, Yu;Trinh Tran;Quinlan, Elizabeth M.
视觉皮层中快速发放中间神经元（FS IN）的兴奋驱动成熟与眼优势可塑性关键期的时间控制有关。然而，调节这些突触在皮层发育过程中的强度的机制还不清楚。在这里，我们使用小鼠模型来显示神经调节蛋白（NRG）和受体酪氨酸激酶erbB 4调节关键期的时间。NRG 1增强了FS INs上兴奋性突触的强度，在关键期抑制了眼优势可塑性，但在转基因低兴奋性FS INs中挽救了可塑性。通过抑制erbB阻断内源性neuregulin的作用挽救了关键期后成人的眼优势可塑性，使慢性单眼剥夺诱导的弱视得以恢复。因此，FS INs的兴奋强度是关键期可塑性的关键决定因素，并通过NRG-erbB 4信号传导维持在高水平，以限制成年期的可塑性。
Maturation of excitatory drive onto fast-spiking interneurons (FS INs) in the visual cortex has been implicated in the control of the timing of the critical period for ocular dominance plasticity. However, the mechanisms that regulate the strength of these synapses over cortical development are not understood. Here we use a mouse model to show that neuregulin (NRG) and the receptor tyrosine kinase erbB4 regulate the timing of the critical period. NRG1 enhanced the strength of excitatory synapses onto FS INs, which inhibited ocular dominance plasticity during the critical period but rescued plasticity in transgenics with hypoexcitable FS INs. Blocking the effects of endogenous neuregulin via inhibition of erbBs rescued ocular dominance plasticity in postcritical period adults, allowing recovery from amblyopia induced by chronic monocular deprivation. Thus, the strength of excitation onto FS INs is a key determinant of critical period plasticity and is maintained at high levels by NRG-erbB4 signaling to constrain plasticity in adulthood.