Global Synaptic Plasticity Mechanisms in Visual Cortex

项目摘要 众所周知，经验依赖的皮层可塑性在生命的早期最为突出，特别是在老年人中。 初级感觉皮层然而，成年人大脑皮层中的不同回路成分保留了它们的能力， 经历可塑性。例如，初级感觉皮层表层的突触在大脑中保持可塑性。 成年人，这与有限的可塑性丘脑皮质输入。确定先天性 成人感觉皮层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，在成年人的初级视觉皮层（V1）选择 兴奋性突触经历可塑性变化，在感觉体验中具有相当短暂的改变。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， 层2/3（L2/3）神经元，而不改变来自层4（L4）的前馈输入的强度。二是 研究发现，耳聋的成年人产生丘脑皮层突触增强到L4神经元在V1内， 周这些发现表明，成人V1具有相当快的先天可塑性，以响应感觉的变化， 体验.在这项提议中，我们的目标是了解成人V1的L2/3的特定输入如何适应视力丧失 (Aim 1），以及其随后恢复的机制（目标2）。此外，我们将确定 成年V1在短暂的耳聋后引起丘脑皮层突触可塑性的机制， 以及是否能增强眼优势可塑性（ODP）（目的3）。我们的工作成果将 了解V1如何适应生命后期感官体验的变化。此外，我们的研究结果将提供 成人V1可塑性的机制的理解，并产生分子工具，以增强或防止这种 以特定的方式改变电路。这些发展最终将使我们能够操纵先天的 可塑性机制存在于成人V1，以促进视力的功能恢复。

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.