Department of Pediatrics, University of California San Francisco, San Francisco, California 94143, USA.
J Neurosci. 2010 Jan 6;30(1):81-92. doi: 10.1523/JNEUROSCI.5656-08.2010.
Ocular dominance plasticity (ODP) following monocular deprivation (MD) is a model of activity-dependent neural plasticity that is restricted to an early critical period regulated by maturation of inhibition. Unique developmental plasticity mechanisms may improve outcomes following early brain injury. Our objective was to determine the effects of neonatal cerebral hypoxia-ischemia (HI) on ODP. The rationale extends from observations that neonatal HI results in death of subplate neurons, a transient population known to influence development of inhibition. In rodents subjected to neonatal HI and controls, maps of visual response were derived from optical imaging during the critical period for ODP and changes in the balance of eye-specific response following MD were measured. In controls, MD results in a shift of the ocular dominance index (ODI) from a baseline of 0.15 to -0.10 (p < 0.001). Neonatal HI with moderate cortical injury impairs this shift, ODI = 0.14 (p < 0.01). Plasticity was intact in animals with mild injury and in those exposed to hypoxia alone. Neonatal HI resulted in decreased parvalbumin expression in hemispheres receiving HI compared with hypoxia alone: 23.4 versus 35.0 cells/high-power field (p = 0.01), with no change in other markers of inhibitory or excitatory neurons. Despite abnormal inhibitory neuron phenotype, spontaneous activity of single units and development of orientation selective responses were intact following neonatal HI, while overall visual responses were reduced. Our data suggest that specific plasticity mechanisms are impaired following early brain injury and that the impairment is associated with altered inhibitory neuronal development and cortical activation.
单眼剥夺后眼部优势可塑性（ODP）是一种依赖于活动的神经可塑性模型，其仅局限于受抑制成熟调节的早期关键期。独特的发育可塑性机制可能会改善早期脑损伤后的结果。我们的目的是确定新生期脑缺氧缺血（HI）对 ODP 的影响。该原理源自以下观察结果：新生期 HI 会导致基板神经元死亡，而基板神经元是一种已知会影响抑制发育的短暂神经元群体。在经历新生期 HI 和对照的啮齿动物中，在 ODP 的关键期期间通过光学成像得出视觉反应图，并测量单眼剥夺后眼特异性反应平衡的变化。在对照组中，单眼剥夺导致眼部优势指数（ODI）从基线 0.15 变为-0.10（p < 0.001）。中度皮质损伤的新生期 HI 会损害这种转变，ODI = 0.14（p < 0.01）。轻度损伤的动物和仅暴露于缺氧的动物中，可塑性完好无损。与仅缺氧相比，接受 HI 的半球中的 parvalbumin 表达减少：23.4 比 35.0 个/高倍视野（p = 0.01），而抑制性或兴奋性神经元的其他标志物没有变化。尽管抑制性神经元表型异常，但新生期 HI 后单个单位的自发活动和定向选择性反应的发育仍然完整，而整体视觉反应减少。我们的数据表明，早期脑损伤后特定的可塑性机制受损，并且这种损伤与抑制性神经元发育和皮质激活改变有关。
