DEVELOPMENT OF SYNAPTIC PLASTICITY IN THE VISUAL CORTEX

大脑皮层突触改变其信号效率的动态能力被认为是学习和经验依赖性修改的许多方面的基础。调节依赖活动的突触可塑性的细胞和分子过程，包括视皮层。这种视皮层突触信号的活动依赖性变化，无论是暂时性的还是持续性的，也被认为有助于视觉输入的动态皮层处理，从而导致视觉知觉、认知表现、技能学习和发育重组以及功能性视觉皮质突触网络的完善。然而，这些形式的突触可塑性的发育调节却较少受到关注。在视皮层，环境养育条件、外周感觉缺陷如视网膜损伤、斜视或形觉障碍等的严重后果已在神经元结构、功能和行为水平上得到证实。我们利用一个新皮质突触可塑性模型(DCM模型)来描述在成熟和新生动物的视觉新皮质中负责一种功能性突触可塑性的细胞过程。我们以前已经发现，这种形式的突触可塑性，或协方差诱导增强(CIP)，发生在成人视皮层的单个锥体神经元中，它是由N-甲基-D-天冬氨酸(NMDA)谷氨酸受体的激活和突触后细胞内钙的升高触发的。与成熟的视皮层相比，CIP在新生儿中的诱导要强得多。然而，触发突触潜力的细胞机制经历了戏剧性的发育转变。触发机制从NMDA受体独立的过程切换到NMDA受体依赖的过程。我们假设，代谢性谷氨酸受体和电压门控钙通道的电压检测之间的耦合机制分别发生了发育受控的变化。我们将通过将电生理技术与高分辨率钙成像相结合来识别这种发育调节可塑性的分子符合探测器和信号级联。

The dynamic capacity for synapses in the cerebral cortex to change their signaling efficiency is thought to underlie many aspects of learning and experience-dependent modification. The cellular and molecular processes that mediate activity-dependent synaptic plasticity including the visual cortex. Such activity-dependent changes in synaptic signaling in the visual cortex, whether of a transient or sustained nature also have been suggested to contribute to dynamic cortical processing of visual input with consequences for visual perception, cognitive performance, skill- learning and developmental re-organization and refinement of functional visual cortical synaptic networks. However, the developmental regulation of these forms of synaptic plasticity has received less attention. In the visual cortex, dramatic consequences of environmental rearing conditions, peripheral sensory deficits such as retinal lesions, strabismus or form vision disturbances have been demonstrated at the level of neuronal structure, function and behavior. We utilize a model of neocortical synaptic plasticity (the DCM model) to characterize the cellular processes that are responsible for a type of functional synaptic plasticity in the visual neo-cortex of mature and neonatal animals. We have previously found that this form of synaptic plasticity, or covariance-induced- potentiation (CIP), occurs in individual pyramidal neurons of the adult visual cortex and it is triggered by activation of the N-methyl-D aspartate (NMDA) glutamate receptors and a rise in postsynaptic intracellular calcium. The induction of CIP is considerably more robust in the neonatal versus the mature visual cortex. However, the cellular mechanism for triggering the synaptic potential undergoes a dramatic developmental switch. The triggering mechanism switches from an NMDA-receptor independent to an NMDA-receptor dependent process. We have posited a developmentally controlled alteration in the coupling mechanism between voltage detection by metabotropic glutamate receptors and voltage-gated calcium channels, respectively. We will identify the molecular coincidence detector and signaling cascade for this type of developmentally regulated plasticity by combining electrophysiological techniques with high-resolution calcium imaging.