Global synaptic plasticity mechanisms in visual cortex

描述（申请人提供）：视觉体验对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后延迟摘除白内障会导致受累眼睛的功能性失明。动物研究表明，这种功能性脱节是由视觉皮层连通性的变化造成的。因此，理解视觉经验依赖的可塑性需要阐明突触修饰的皮质机制。

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.