Global synaptic plasticity mechanisms in visual cortex

视觉皮层的整体突触可塑性机制

• 批准号: 7037401
• 负责人: Hey-Kyoung Lee
• 金额: $ 29万
• 依托单位: UNIV OF MARYLAND, COLLEGE PARK
• 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 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7037401
• 关键词: AMPA receptors; brain electrical activity; electrophysiology; genetically modified animals; immunocytochemistry; laboratory mouse; light adaptations; long term potentiation; neural plasticity; neural transmission; neuroanatomy; neurogenesis; neuroregulation; phosphorylation; protein structure function; receptor expression; synapses; visual cortex; visual deprivation; visual stimulus

DESCRIPTION (provided by applicant): Visual experience is critical for proper development and function of the visual cortex. For example, delayed removal of cataracts beyond a critical period in childhood results in functional blindness of the affected eye. Animal studies have shown that this functional disconnection results from changes in connectivity of the visual cortex. Therefore, understanding visual experience-dependent plasticity requires elucidation of cortical mechanisms of synaptic modification. There are two identified mechanisms of synaptic modification in the visual cortex. One type of mechanism is by altering connectivity at specific synapses, such as long-term potentiation (LTP) and long-term depression (LTD). The other affects synaptic strengths globally within a cell. This type of global plasticity occurs on a slower time scale, and has been implicated in acting as a negative feedback mechanism that stabilizes neural networks. The cellular mechanisms that underlie synapse-specific plasticity have received much attention. However, relatively little is known regarding the mechanisms of global plasticity. We found that rearing animals in the dark increases the size of AMPA receptor-mediated synaptic responses, similar to the results from a recent visual deprivation study. These results indicate that chronic visual deprivation can globally up-regulate excitatory synaptic strength in vivo. In addition, we found that dark rearing increases phosphorylation of AMPA receptors at specific sites. In this proposal, we intend to investigate the involvement of AMPA receptor phosphorylation in global synaptic plasticity. The results from the proposed study will provide insights into how visual experience acts globally to change synaptic strength at a molecular level. The knowledge gained from our work can be generalized to further our understanding of how neural circuits are sculpted by activity during development and by experience.

描述（由申请人提供）：视觉体验对于视觉皮层的正常发育和功能至关重要。例如，在儿童时期的关键时期之后延迟去除白内障会导致受影响的眼睛功能性失明。动物研究表明，这种功能性脱节是由于视觉皮层连接性的变化造成的。因此，理解视觉体验依赖性可塑性需要阐明突触修饰的皮质机制。 视觉皮层中存在两种已确定的突触修饰机制。一种机制是通过改变特定突触的连接性，例如长期增强（LTP）和长期抑制（LTD）。另一个影响细胞内全局的突触强度。这种类型的全局可塑性发生在较慢的时间尺度上，并且与稳定神经网络的负反馈机制有关。突触特异性可塑性背后的细胞机制受到了广泛关注。然而，人们对整体可塑性的机制知之甚少。我们发现，在黑暗中饲养动物会增加 AMPA 受体介导的突触反应的大小，这与最近的视觉剥夺研究的结果相似。这些结果表明，慢性视觉剥夺可以全面上调体内兴奋性突触强度。此外，我们发现黑暗饲养会增加特定位点 AMPA 受体的磷酸化。在本提案中，我们打算研究 AMPA 受体磷酸化在整体突触可塑性中的参与。拟议研究的结果将深入了解视觉体验如何在全球范围内发挥作用，从而在分子水平上改变突触强度。从我们的工作中获得的知识可以推广到进一步我们对神经回路如何通过发育过程中的活动和经验进行塑造的理解。