Recovering plasticity in adult ferret V1 by cross-modal deprivation

通过跨模式剥夺恢复成年雪貂 V1 的可塑性

• 批准号: 9050034
• 负责人: Hey-Kyoung Lee
• 金额: $ 24.46万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-30 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9050034
• 关键词: Adult; Age; Amblyopia; Animal Model; Biological Models; Blindness; Chemosensitization; Chronic; Clinical; Development; Early Intervention; Evoked Potentials; Excision; Eye; Ferrets; Human; Intervention; Lateral Geniculate Body; Life; Long-Term Depression; Measures; Methods; Modality; Mus; Neurons; Ocular Dominance; Ocular dominance columns; Primates; Process; Proteinase 3; Recovery; Reporting; Resistance; Rodent; Sensory; Sensory Deprivation; Site; Study models; Synapses; Testing; Time; Ursidae Family; V1 neuron; Vision; Visual; Visual Acuity; area striata; base; congenital cataract; critical period; deprivation; experience; genetic manipulation; interest; intervention effect; monocular; monocular deprivation; optogenetics; orientation selectivity; postnatal; public health relevance; relating to nervous system; response; sensory cortex; tool; visual deprivation; visual plasticity

 DESCRIPTION (provided by applicant): Long-term monocular deprivation (MD) initiated before any visual experience leads to permanent loss of vision through the occluded eye, and is much more resistant to recovery later in life compared to MD initiated after a period of normal vision. At a functional and anatomical level, it is known that long-term MD leads to a shift in ocular dominance (OD) in the primary visual cortex (V1). In particular, V1 neurons lose responses from the deprived eye, which are thought to result from mechanisms resembling long-term depression (LTD). While recent studies have reported recovery from long-term MD using either genetic manipulations or invasive pharmacological interventions, these cases have been limited to long-term MD after about a week of normal vision during early development. Studies have shown that MD initiated before eye opening in diverse animal models is much more resilient to recovery, and is thought to involve changes in thalamocortical (TC) inputs to V1. Hence methods to recover plasticity at TC synapses would benefit recovery from chronic long-term MD without initial vision. We recently found that deafening adult mice for a brief duration leads to potentiation of TC synapses in layer 4 (L4) of V1. Here we propose to examine whether deafening adult ferrets for a brief duration would allow cross-modal potentiation of TC synapses in V1 to promote recovery from chronic long-term MD initiated before eye opening. Ferret V1 is organized similar to humans with OD columns and orientation pinwheels, which overcomes the limits of mouse V1 lacking such modular organization. To test our hypothesis that deafening promotes TC plasticity in adult ferret V1, we will utilize channelrhodopsin based optogenetic tools to quantitatively measure the strength of TC synapses in L4 of V1 with or without deafening (Aim 1). In addition, intracortical synaptic strength in L4 will be quantified. T investigate whether cross-modal potentiation of TC synapses promotes recovery from chronic long-term MD, we will compare V1 neuronal functions, including OD and visual acuity, using multi-site laminar recording probes (Aim 2). The results from our study will determine whether cross-modal sensory deprivation in adults would promote recovery from chronic long-term MD by restoring TC plasticity. Our results could be generalized to promote recovery from sensory loss in other modalities, and pave a way to develop non-invasive means to recover from deprivation amblyopia in adults.

 描述（由申请人提供）：在任何视觉体验之前开始的长期单眼剥夺（MD）会导致闭塞眼视力永久丧失，并且与正常一段时间后开始的单眼剥夺相比，在以后的生活中更难以恢复。在功能和解剖水平上，众所周知，长期的 MD 会导致初级视觉皮层 (V1) 的眼优势 (OD) 发生变化，特别是 V1 神经元会失去被剥夺的眼睛的反应。人们认为这是由类似于长期抑郁症 (LTD) 的机制引起的，虽然最近的研究报告使用基因操作或侵入性药物干预从长期 MD 中恢复，但这些病例仅限于大约一周后的长期 MD。研究表明，在不同的动物模型中，在睁眼之前开始的 MD 的恢复能力要强得多，并且被认为涉及丘脑皮质 (TC) 对 V1 的输入的变化，因此需要恢复 TC 突触的可塑性。我们最近发现，使成年小鼠短暂耳聋会导致 V1 第 4 层 (L4) 的 TC 突触增强。短暂的持续时间将允许 V1 中的 TC 突触的跨模式增强，以促进从睁眼之前开始的慢性长期 MD 的恢复，Ferret V1 的组织方式类似于具有 OD 柱和定向风车的人类，它克服了小鼠 V1 缺乏这种模块化组织的限制，为了检验我们的假设，即震耳欲聋会促进成年雪貂 V1 的 TC 可塑性，我们将利用基于视紫红质的光遗传学工具来定量测量有或没有震耳欲聋的 V1 的 L4 中 TC 突触的强度。目标 1) 此外，将量化 L4 的皮质内突触强度，以研究 TC 突触的跨模式增强是否会促进。为了从慢性长期 MD 中恢复，我们将使用多位点层流记录探针比较 V1 神经元功能，包括 OD 和视力（目标 2）。我们的研究结果将确定成人的跨模式感觉剥夺是否会促进。通过恢复 TC 可塑性从慢性长期 MD 中恢复我们的结果可以推广到其他方式中促进感觉丧失的恢复，并为开发非侵入性手段从剥夺中恢复铺平道路。成人弱视。