Developmental Neuroscience Program, Saban Research Institute, Children's Hospital Los Angeles, Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA 90027, USA.
Department of Anatomical Sciences and Neurobiology, School of Medicine, University of Louisville, Louisville, KY 40202, USA.
Curr Biol. 2020 Aug 3;30(15):2962-2973.e5. doi: 10.1016/j.cub.2020.05.067. Epub 2020 Jun 25.
Disrupting binocular vision during a developmental critical period can yield enduring changes to ocular dominance (OD) in primary visual cortex (V1). Here we investigated how this experience-dependent plasticity is coordinated within the laminar circuitry of V1 by deleting separately in each cortical layer (L) a gene required to close the critical period, nogo-66 receptor (ngr1). Deleting ngr1 in excitatory neurons in L4, but not in L2/3, L5, or L6, prevented closure of the critical period, and adult mice remained sensitive to brief monocular deprivation. Intracortical disinhibition, but not thalamocortical disinhibition, accompanied this OD plasticity. Both juvenile wild-type mice and adult mice lacking ngr1 in L4 displayed OD plasticity that advanced more rapidly L4 than L2/3 or L5. Interestingly, blocking OD plasticity in L2/3 with the drug AM-251 did not impair OD plasticity in L5. We propose that L4 restricts disinhibition and gates OD plasticity independent of a canonical cortical microcircuit.
在发育关键期扰乱双眼视觉会导致初级视觉皮层 (V1) 中的眼优势 (OD) 产生持久变化。在这里，我们通过在每个皮层层 (L) 中分别删除关闭关键期所需的基因，即神经生长抑制因子-66 受体 (ngr1)，来研究这种经验依赖性可塑性如何在 V1 的层状电路中协调。在 L4 中的兴奋性神经元中删除 ngr1，但不在 L2/3、L5 或 L6 中删除，可防止关键期的关闭，并且成年小鼠仍然对短暂的单眼剥夺敏感。伴随这种 OD 可塑性的是皮层内抑制的解除，而不是丘脑皮质抑制的解除。幼年野生型小鼠和 L4 中缺乏 ngr1 的成年小鼠均表现出 OD 可塑性，L4 的 OD 可塑性比 L2/3 或 L5 更快地进展。有趣的是，用药物 AM-251 阻断 L2/3 中的 OD 可塑性不会损害 L5 中的 OD 可塑性。我们提出 L4 限制了去抑制并独立于经典皮层微电路来控制 OD 可塑性。
