Mechanical properties of perineuronal nets and their effect on synaptic plasticity

本研究旨在利用原子力显微镜（AFM）研究成年PNN神经元的力学性质（刚度、弹性），并探讨PNN神经元的力学性质是否影响与PNN神经元接触的突触数量。PNN是中枢神经系统（CNS）中包裹神经元的浓缩细胞外基质结构。它们出现在中枢神经系统的自然发育过程中，并终止中枢神经系统的幼年可塑性。PNN如何导致这种塑性限制仍在研究中。一种理论是PNN充当来自其他神经元的突触连接的机械屏障，从而降低突触可塑性。已知生腱蛋白-R和连接蛋白交联PNN的组分，因此可以赋予PNN刚性。我们将研究敲除这些蛋白质是否会影响PNN的机械性能。这些结果将使我们更好地了解中枢神经系统内突触可塑性的基本生物学过程，以及交联分子的表达对其的调节。理解突触可塑性涉及理解学习和记忆的分子基础，以及异常可塑性疾病，即成瘾，创伤后应激障碍。这是一个跨学科的项目，其中将开发AFM方法来研究神经元及其周围的PNN的机械生物学，这是以前没有实现的。

This project aims to use atomic force microscopy (AFM) to probe the mechanical properties (stiffness, elasticity) of adult PNN-bearing neurons and to investigate if mechanical properties of the PNNs affect number of synapses contacting the PNN-neuron.PNNs are condensed extracellular matrix structures that encase neurons in the central nervous system (CNS). THey appear during natural development and terminate periods of juvenile plasticity in the CNS. How the PNNs cause this restriction of plasticity is still being investigated. One theory is that the PNNs act as a mechanical barrier to synaptic connections from other neurons thus reducing synaptic plasticity. Tenascin-R and link proteins are known to cross-link components of the PNNs and thus may confer rigidity to PNNs. We shall investigate if knocking out these proteins would effect the mechanical properties of the PNN. The results will allow us a better understanding of the basic biological process of synaptic plasticity within the CNS, and its modulation by the expression of cross-linking molecules. Understanding synaptic plasticity relates to understanding the molecular basis for learning and memory, and also diseases of aberrant plasticity i.e. addiction, post-traumatic stress disorder. This is an interdisciplinary project in which AFM methods will be developed to study the mechanobiology of neurons and the PNNs surrounding them, which has not previously been achieved.