Global Synaptic Plasticity Mechanisms in Visual Cortex

项目摘要 众所周知，依赖经验的皮质可塑性在生命早期最为突出，尤其是在 初级感觉皮质。然而，成人大脑皮质中不同的回路组件保留了它们的能力 经历可塑性。例如，大脑初级感觉皮质表层的突触仍然是可塑性的。 这将丘脑皮质的输入与有限的可塑性进行了对比。先天机制的确定 成人感觉皮质中存在的可塑性将使我们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，在成人初级视皮层(V1)中， 兴奋性突触经历了可塑性变化，感觉体验也发生了相当短暂的变化。首先，我们发现 视觉体验的短暂变化优先改变外侧皮质内突触的强度 层2/3(L2/3)神经元，不改变来自层4(L4)的前馈输入强度。第二，我们 研究发现，耳聋的成年人在一周内产生丘脑皮质突触对V1中L4神经元的增强作用 星期。这些发现表明，成年V1对感觉变化有相当快的先天可塑性 经验。在这项建议中，我们的目标是了解成人V1的L2/3的特定输入如何适应失明 (目标1)，以及随后恢复的机制(目标2)。此外，我们将确定 短暂耳聋后成人V1区丘脑皮质突触可塑性的机制 是否能增强眼优势可塑性(ODP)(目标3)。我们的工作成果将会消失。 关于V1如何适应生命后期感官体验的变化。此外，我们的结果将提供 从机制上理解成人V1的可塑性，并产生分子工具来增强或防止这种情况 以特定于电路的方式改变。这些发展最终将允许我们操纵先天 成人V1中存在促进视力功能恢复的可塑性机制。

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.