Global Synaptic Plasticity Mechanisms in Visual Cortex

视觉皮层的整体突触可塑性机制

• 批准号: 9549159
• 负责人: Hey-Kyoung Lee
• 金额: $ 3.84万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9549159
• 关键词: Adolescent; Adult; Age; Brain; Chemosensitization; Darkness; Data; Depressed mood; Development; Excitatory Synapse; Genetic; Homer 1a; Lateral; Life; Light; Mediating; Mental Depression; Modality; Molecular; Mus; Nerve Degeneration; Neurons; Ocular Dominance; Plasticizers; Process; Recovery; Recovery of Function; Regulation; Reporting; Sensory; Sensory Deprivation; Signal Transduction; Source; Stroke; Synapses; Synaptic plasticity; Testing; Trauma; Vision; Visual; Visual Cortex; Work; area striata; base; critical period; experience; hippocampal pyramidal neuron; insight; metabotropic glutamate receptor 5; optogenetics; postnatal; prevent; response; sensory cortex; sensory input; tool; visual deprivation

Project Summary It is well established that experience-dependent cortical plasticity is most prominent early in life, especially in the primary sensory cortices. However, distinct circuit components in the adult cortex retain their ability to undergo plasticity. For example, synapses in the superficial layers of primary sensory cortices remain plastic in adults, which contrasts thalamocortical inputs with limited plasticity. Determining the mechanisms of innate plasticity present in the adult sensory cortices will allow us to understand how the adult brain adapts to changes in sensory experience. We recently found evidence that in adult primary visual cortex (V1) select excitatory synapses undergo plastic changes with rather brief alterations in sensory experience. First, we found that brief alterations in visual experience preferentially changes the strength of lateral intracortical synapses to layer 2/3 (L2/3) neurons without changes in the strength of feedforward inputs from layer 4 (L4). Second, we found that deafening adults produces potentiation of thalamocortical synapses onto L4 neurons in V1 within a week. These findings suggest that adult V1 has rather rapid innate plasticity in response to changes in sensory experience. In this proposal, we aim to understand how specific inputs to L2/3 of adult V1 adapt to losing vision (Aim 1), and the mechanisms underlying their subsequent recovery (Aim 2). In addition, we will determine the mechanisms of thalamocortical synaptic plasticity elicited in adult V1 following a brief duration of deafening, and whether it can enhance ocular dominance plasticity (ODP) (Aim 3). The results from our work will shed light on how V1 adapts to changes in sensory experience later in life. Furthermore, our results will provide mechanistic understanding of adult V1 plasticity, and generate molecular tools to enhance or prevent such changes in a circuit specific manner. These developments will ultimately allow us to manipulate innate plasticity mechanisms present in adult V1 to promote functional recovery of vision.

项目概要 众所周知，依赖于经验的皮质可塑性在生命早期最为突出，尤其是在 初级感觉皮层。然而，成人皮层中不同的电路组件保留了它们的能力 经历可塑性。例如，初级感觉皮层表层的突触在 成人，这将丘脑皮质​​输入与可塑性有限形成对比。确定先天机制 成人感觉皮层中存在的可塑性将使我们能够了解成人大脑如何适应 感官体验的变化。我们最近发现的证据表明，在成人初级视觉皮层（V1）中选择 兴奋性突触经历塑性变化，感觉体验发生相当短暂的改变。首先，我们发现 视觉体验的短暂改变优先改变外侧皮质内突触的强度 第 2/3 层 (L2/3) 神经元不改变第 4 层 (L4) 的前馈输入强度。第二，我们 发现震耳欲聋的成年人在 V1 的 L4 神经元上产生丘脑皮质突触的增强作用 星期。这些发现表明，成人 V1 对感官变化具有相当快的先天可塑性 经验。在本提案中，我们的目标是了解成人 V1 L2/3 的特定输入如何适应视力丧失 （目标 1），以及随后恢复的机制（目标 2）。此外，我们将确定 成人V1在短暂的震耳欲聋后引发丘脑皮质突触可塑性的机制， 以及是否可以增强眼部优势可塑性（ODP）（目标 3）。我们的工作成果将会流淌 阐明 V1 如何适应以后生活中感官体验的变化。此外，我们的结果将提供 对成人 V1 可塑性的机制理解，并生成分子工具来增强或防止这种情况 以电路特定方式改变。这些发展最终将使我们能够操纵先天 成人 V1 中存在促进视力功能恢复的可塑性机制。