Alignment of visual features in binocular cortical circuits through experience dependent synaptic plasticity

通过经验依赖的突触可塑性调整双眼皮层回路中的视觉特征

• 批准号: 10534839
• 负责人: Katherine Rachel Tsimring
• 金额: $ 4.68万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-30 至 2025-12-29
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10534839
• 关键词: AMPA Receptors; Address; Amblyopia; Binocular Vision; Brain; Calcium; Chemosensitization; Chronic; Computer Models; Contralateral; Dendritic Spines; Development; Excision; Exhibits; Eye; Functional Imaging; Functional disorder; Future; Glutamates; Guanosine Triphosphate Phosphohydrolases; Image; Impairment; Individual; Ipsilateral; Lead; Link; Maps; Measures; Mediating; Modification; Molecular; Molecular Analysis; Mus; Nature; Neurodevelopmental Disorder; Neurons; Ocular Dominance; Physiological; Property; Proteins; Proteome; Research; Resolution; Scaffolding Protein; Schizophrenia; Sensory; Sensory Process; Shapes; Structure; Synapses; Synaptic plasticity; Techniques; Technology; Testing; Tissue Expansion; Tissues; Vertebral column; Visual; Visual Cortex; Visual impairment; Visual system structure; Work; area striata; autism spectrum disorder; awake; base; critical developmental period; critical period; deprivation; experience; experimental study; in vivo; in vivo calcium imaging; insight; monocular deprivation; neural circuit; neuron development; neuronal cell body; novel; orientation selectivity; postnatal development; postsynaptic; postsynaptic neurons; prevent; response; two-photon; visual information; visual tracking

Summary Experience with the external world is essential for fine-tuning immature sensory circuits during critical periods in development. In visual systems, experience regulates the alignment of visual information from the ipsilateral and contralateral eye onto neurons in the binocular primary visual cortex (bV1). At the onset of the critical period for binocular vision, bV1 neurons respond to distinct orientation preferences to each eye. With visual experience, synaptic inputs from each eye get modified, and bV1 neurons develop matching orientation preferences. Disrupting visual experience during this critical period, however, can elicit severe impairments in binocular vision, causing amblyopia. It remains unclear how synaptic inputs are modified to regulate the development of orientation matching in bV1 neurons. Hebbian and heterosynaptic plasticity are mechanisms of experience- dependent plasticity that modify synaptic inputs based on the correlation of pre- and postsynaptic neuronal responses and on the activity of neighboring synapses, respectively. Together, these two mechanisms can shape the selectivity of neuronal responses by strengthening synapses that are correlated with the postsynaptic neuron or with synaptic neighbors, and by weakening those that are uncorrelated. I hypothesize that Hebbian and heterosynaptic mechanisms regulate the alignment and plasticity of eye-specific inputs onto bV1 neurons over the critical period. To test this hypothesis, I will chronically image the visual responses of the neuronal soma and of dendritic spines using in vivo two-photon calcium imaging to track eye-specific inputs on L2/3 bV1 neurons. I will then map the synaptic composition of the physiologically identified dendritic spines post hoc by implementing a novel tissue expansion technology called Magnified Analysis of the Proteome (MAP) that allows for super-resolution imaging of intact tissue. I will combine these cutting-edge technologies in my two aims to delineate how the alignment of somatic orientation preference arises through synaptic remodeling of eye-specific inputs. In Aim 1, I will characterize the functional, structural, and molecular properties of eye-specific inputs across development to determine whether Hebbian and heterosynaptic plasticity is taking place during somatic orientation matching. In Aim 2, I will deprive the contralateral eye of visual experience using monocular deprivation (MD) to determine how disruptions in binocular vision impact eye-specific inputs on bV1 neurons. Together, these experiments will answer fundamental questions on the nature of experience-dependent plasticity in the binocular visual cortex. Furthermore, these studies will provide critical insight into the synaptic basis of amblyopia, as well as neurodevelopmental disorders that are induced by synaptic dysfunction.

总结 与外部世界的经验是必不可少的微调不成熟的感觉电路在关键时期， 发展在视觉系统中，经验调节来自同侧的视觉信息的对齐， 对侧眼对双眼初级视觉皮层（bV 1）中的神经元的影响。在关键时期开始时， 双眼视觉，bV 1神经元对每只眼睛的不同方向偏好做出反应。有了视觉体验， 来自每只眼睛的突触输入被修改，bV 1神经元发展出匹配的方向偏好。 然而，在这个关键时期中断视觉体验会导致双眼视觉严重受损， 导致弱视。目前尚不清楚突触输入是如何被修饰以调节神经元的发育的。 bV 1神经元的方向匹配。赫布可塑性和异突触可塑性是经验的机制- 依赖性可塑性，根据突触前和突触后神经元的相关性来修改突触输入 反应和相邻突触的活动，分别。这两种机制结合起来， 通过加强与突触后神经元相关的突触来塑造神经元反应的选择性。 神经元或突触邻居，并通过削弱那些不相关的。我假设赫比安 异突触机制调节bV 1上眼特异性输入的排列和可塑性 关键时期的神经元。为了验证这一假设，我将长期想象的视觉反应， 神经元索马和树突棘使用体内双光子钙成像跟踪眼睛特异性输入 L2/3bV 1神经元。然后我将绘制生理上鉴定的树突棘的突触组成， 通过实施一种称为蛋白质组的磁共振分析（MAP）的新型组织扩张技术， 允许对完整组织进行超分辨率成像。我将联合收割机这些尖端技术结合在我的两个 旨在描述躯体方向偏好的排列如何通过突触重塑产生 眼睛特定的输入。在目标1中，我将描述眼睛特异性的功能，结构和分子特性。 输入，以确定Hebbian和异突触可塑性是否发生在发育过程中， 躯体方向匹配在目标2中，我将使用单眼剥夺对侧眼睛的视觉体验， 剥夺（MD），以确定双眼视觉的破坏如何影响bV 1神经元上的眼睛特异性输入。 这些实验将共同回答有关经验依赖性可塑性本质的基本问题 在双眼视觉皮层。此外，这些研究将提供关键的洞察突触的基础， 弱视以及由突触功能障碍引起的神经发育障碍。