Regulation of Synaptic Plasticity in Visual Cortex

描述（由申请人提供）：长期以来，人们一直认为，早期关键时期的视觉体验对于视觉皮层的正常成熟至关重要。对在不同环境中饲养的动物的研究已经确定，在这个关键时期，视觉皮层连接可以以活动依赖的方式进行修改。这些研究还表明，视觉皮层的可塑性取决于神经调制系统和皮层内抑制的强度。本项目的长期目标是阐明年龄、神经调质和突触抑制控制视皮层突触修饰的细胞机制。该提案的重点是两种形式的突触修饰的调节，被认为是参与自然发生的可塑性：长时程增强（LTP）和长时程抑制（LTD）。这些研究的目的是测试两个假设，关于神经调节剂和突触抑制如何调节这些形式的可塑性的诱导。第一个假设指出，特定的神经调质是必不可少的选择性门控或启动诱导的LTP和LTD。第二个假设指出，发展增加突触抑制的强度减少或防止诱导的LTP和LTD。实验将在切片中进行从不同年龄的大鼠和小鼠的视觉皮层，并提出在不同的环境。LTP和LTD的变化将与自然发生的突触修饰的变化进行比较。了解LTP和LTD是如何调节的，将有助于深入了解关键期的机制，并将提供对皮质可塑性整合方面的细胞理解。除了这种神经可塑性与视觉能力的发展明显相关之外，类似的过程似乎可能构成成人大脑中某些形式的学习和记忆的基础。

DESCRIPTION (provided by applicant): It has long been appreciated that visual experience during an early critical period is essential for the normal maturation of visual cortex. Studies on animals reared in different environments have established that during this critical period, visual cortical connections can be modified in an activity dependent manner. Those studies have also shown that visual cortical plasticity depends on neuromodulary systems and on the strength of intracortical inhibition. The long-term goal of this project is to elucidate the cellular mechanisms by which age, neuromodulators and synaptic inhibition control synaptic modification in visual cortex. This proposal focuses on the regulation of two forms of synaptic modification that are believed to be involved in natural occurring plasticity: long-term potentiation (LTP) and long-term depression (LTD). The studies are aimed to test two hypotheses concerning how neuromodulators and synaptic inhibition might regulate the induction of these forms of plasticity. The first hypothesis states that specific neuromodulators are essential to selectively gate or prime the induction of LTP and LTD. The second hypothesis states that developmental increases in the strength of synaptic inhibition reduces or prevents the induction of LTP and LTD. The experiments will be performed in slices made from the visual cortex of rats and mice of different ages and raised in different environments. Changes in LTP and LTD will be compared with reported changes in naturally-occurring synaptic modifications. Understanding how LTP and LTD are regulated will yield insights into the mechanisms underlying the critical period and will provide a cellular understanding of the integrative aspects of cortical plasticity. Besides the obvious relevance of this neural plasticity to the development of visual capabilities, it seems likely that similar processes may form the basis for some forms of learning and memory in the adult brain.