Cross modal plasticity following loss of vision at different developmental stages: Cortical function, connections and compensatory behavior

不同发育阶段视力丧失后的跨模式可塑性：皮质功能、连接和补偿行为

• 批准号: 10504252
• 负责人: LEAH ANN KRUBITZER
• 金额: $ 37.18万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10504252
• 关键词: Acoustic Stimulation; Acute; Address; Adult; Affect; Age; Age of Onset; Anatomy; Animal Model; Animals; Area; Auditory; Axon; Behavior; Behavioral; Bilateral; Birth; Blindness; Body part; Brain; Cannulas; Child; Complex; Data; Development; Didelphidae; Discrimination; Electrophysiology (science); Embryo; Environment; Eye; Failure; Forelimb; Gene Targeting; Impairment; Implant; Injections; Laboratories; Life; Link; Mammals; Mediating; Microinjections; Modality; Monodelphis; Monodelphis Domestica; Movement; Mus; Muscimol; Neocortex; Nervous system structure; Neurons; Organ; Pathway interactions; Performance; Play; Property; Retina; Retinal Ganglion Cells; Role; Sensory; Shapes; Skin; Somatosensory Cortex; Stimulus; Tactile; Task Performances; Texture; Thalamic Nuclei; Therapeutic Intervention; Time; Tracer; Training; Vibrissae; Vision; Visual; Walking; area V1; area striata; auditory processing; auditory stimulus; base; behavior prediction; behavior test; behavioral outcome; blind; experimental study; extrastriate visual cortex; fluorophore; grasp; in utero; kinematics; machine learning algorithm; mature animal; multimodality; new growth; novel; premature; relating to nervous system; response; retina implantation; retinogeniculate; sensory input; sensory system; somatosensory; targeted treatment

A distinguishing feature of the mammalian neocortex is its remarkable ability to change over a lifetime, particularly during early development. The development of cortical fields and their connections is highly dependent on the incoming sensory inputs they receive from the various sensory organs, such as the eyes and the skin. This input, together with the unique combinations of sensory information available in the environment shapes the neocortex to generate optimal behavior. We know from previous studies in our own laboratory that very early loss of input from the eyes leads to massive changes in the brain, such that all of what would normally be the primary visual cortex (V1) contains neurons that respond to somatosensory and auditory stimulation. This reorganized V1 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? 2) What are single-neuron response properties in reorganized V1 and S1, and does age of blindness onset impact these properties? 3) What is the relationship between functional and anatomical changes in V1 and S1 and compensatory behaviors mediated by the spared sensory systems? Our animal model, the short-tailed opossum, is highly altricial at birth (equivalent to embryonic day 11 in the mouse), allowing ex utero manipulations to the nervous system at developmental time points that would be in utero in other mammals. In these experiments, bilateral enucleations will be made at specific developmental milestones: 1) Prior to the onset of spontaneous activity in the retina, before retinal ganglion cells have reached their subcortical targets, and before thalamocortical axons have innervated the neocortex; 2) When spontaneous activity in the retina is present and retinogeniculate and thalamocortical axons have innervated their targets; 3) Just after eye opening, when sensory driven activity in the retina is present and thalamocortical and corticocortical connections have formed. Following enucleations, animals will be assessed at several different time points. These studies are novel in scope in that they interrogate how the of age of vision loss affects the reorganization of brain circuits and behavior, and if functional and anatomical changes to the neocortex are linked to compensatory behavior. These data can direct therapeutic interventions (e.g. tactile training based behavior), and even allow predictions for behavioral outcomes following retinal implants or gene targeted therapies performed at different ages.

哺乳动物新皮层的一个显着特征是其一生中改变的显着能力， 特别是在早期发展期间。皮质领域及其连接的发展很高 取决于他们从各种感觉器官（例如眼睛）中收到的感官输入 皮肤。此输入以及环境中可用的感官信息的独特组合 塑造新皮层以产生最佳行为。我们从以前在我们自己的实验室的研究中知道 眼睛的早期输入丧失会导致大脑的巨大变化，从而使所有将会发生的一切 通常是主要视觉皮层（V1）包含对体感和听觉响应的神经元 刺激。该重组的V1接收来自丘脑核和皮质场的异位输入 体感和听觉处理。当前的提案解决了几个基本问​​题 这些先前的发现提出：1）盲目发作年龄如何差异影响皮质 连接？ 2）重组V1和S1中的单神经元响应属性是什么，并且年龄的年龄 失明发作会影响这些特性？ 3）功能和解剖学之间的关系是什么 V1和S1的变化以及由不幸的感觉系统介导的代偿行为？我们的动物 模型是短尾泥负鼠，出生时高度非常卑鄙（相当于小鼠的胚胎第11天）， 在发育时间点允许子宫内的神经系统操纵 其他哺乳动物。在这些实验中，将在特定的发育中进行双边摘除 里程碑：1）视网膜神经节细胞在视网膜自发活动发作之前 达到了皮层靶标，在丘脑皮层轴突已经支配了新皮层。 2）何时 视网膜中的自发活性存在，视网膜生成和丘脑皮层轴突已支配 他们的目标； 3）在开眼界之后，当存在视网膜中的感觉驱动活动并且丘脑皮层时 并形成了皮质皮层连接。摘除后，将在几个地方评估动物 不同的时间点。这些研究在范围上是新颖的，因为它们质疑视力丧失的年龄如何 影响脑电路和行为的重组，以及是否功能和解剖学变化 新皮层与补偿行为有关。这些数据可以指导治疗干预措施（例如触觉 基于训练的行为），甚至可以预测视网膜植入物或基因后的行为结果 靶向疗法在不同年龄进行。