Cross-modal plasticity after the loss of vision at two early developmental ages in the posterior parietal cortex: Adult connections, cortical function and behavior.

哺乳动物的新大脑皮层在一生中具有非凡的改变能力，特别是在早期 发展。大脑皮层、感觉场的发育和它们之间的联系依赖于 从外围感官感受器传入的感官输入。这种早期的、自发的感觉 输入，与来自环境的感觉体验一起塑造新皮质，以产生最佳的 行为。我们从对人类和啮齿动物的研究中得知，早期失明会导致大量 大脑的变化；正常情况下视觉和顶叶后皮质区域包含 仅对躯体感觉和听觉刺激有反应的神经元。重组后的枕叶皮质 从丘脑核团和与躯体感觉相关的皮质区接受异位输入 听觉处理。目前的提案解决了以下几个基本问题 以前的发现：1)失明的发病年龄如何不同地影响大脑皮质的连通性 顶叶后皮质的内侧部和侧部(PPCL和PPCM)？2)什么是 PPCM和PPCL的单神经元反应特性以及失明发病年龄是否有影响 这些特性？3)功能和解剖变化与PPCL和PPCL PPCM和备用感觉系统介导的代偿行为？在这些 高品位短尾负鼠双眼摘除实验研究 将在两个发育里程碑进行：1)在视网膜开始自发活动之前， 在视网膜膝状轴突到达丘脑之前，在丘脑皮质轴突神经支配之前 新皮质；2)当视网膜中的自发活动正在进行并生成视网膜时， 丘脑皮质轴突已经支配了它们的目标。在摘除眼球后，动物将在 两个时间点，使我们能够直接评估失明对重要发育的影响 里程碑。这些数据可以指导治疗干预，以补偿视力的丧失 目标是更高级的皮质功能。

The mammalian neocortex has a remarkable ability to change over a lifetime, particularly during early development. The development of the cortex, sensory fields and their connections are dependent on the incoming sensory inputs from the sensory receptors in the periphery. This early, spontaneous sensory input, together with sensory experience from the environment shapes the neocortex to generate optimal behavior. We know from studies in humans and rodents that early loss of vision leads to massive changes in the brain; what would normally be visual and posterior parietal cortical areas contains neurons that respond only to somatosensory and auditory stimulation. This reorganized occipital cortex receives ectopic input from thalamic nuclei and cortical fields associated with somatosensory and auditory processing. The current proposal addresses several fundamental questions raised by these previous findings: 1) How does the age of onset of blindness differentially impact cortical connectivity of the medial and lateral divisions of the posterior parietal cortex (PPCL and PPCM)? 2) What are the single-neuron response properties in PPCM and PPCL, and does the age of blindness onset impact these properties? 3) What is the relationship between functional and anatomical changes PPCL and PPCM and the compensatory behaviors mediated by the spared sensory systems? In these experiments, bilateral enucleations in the highly altricial short-tailed opossum (Monodelphis domestica) will be made at two developmental milestones: 1) Prior to the onset of spontaneous activity in the retina, before retinal geniculate axons reach the thalamus, and before thalamocortical axons have innervated the neocortex; 2) When spontaneous activity in the retina is ongoing and retinogeniculate and thalamocortical axons have innervated their targets. Following enucleations, animals will be assessed at two time points allowing us to directly assess the impacts of blindness at important developmental milestones. These data can direct therapeutic interventions to compensate for the loss of vision that targets higher-order cortical function.