Extracellular matrix regulation of neuronal structure, function, and plasticity

在接下来的五年里，我的研究小组将研究包围大脑细胞的组织基质是如何调节大脑活动的。我们将专注于细胞外基质成分，称为神经周围网络（PNNs），以确定它们对皮层区域局部神经元网络活动的影响，这些区域对认知行为（思维过程、注意力、记忆）和感觉知觉很重要。值得注意的是，pnn调节大脑在发育过程中适当连接自身的能力。我们实验室最近的研究表明，在局灶性损伤后，pnn在正在自我修复的皮层中减少，这表明pnn的减少可能有助于大脑的重新连接。然而，pnn也保护神经元免受损伤，死后研究表明，精神分裂症患者的皮层中pnn减少。我们最近证明，在精神分裂症模型中，pnn的丢失发生在大鼠的皮质中。此外，我们已经直接证明了皮层中pnn的消化会导致认知障碍。因此，PNN的完整性与皮层的功能之间存在明确的关系，但对于PNN的变化如何影响神经元的活动知之甚少。有趣的是，皮层中的大多数pnn与“抑制性”神经元有关，这对降低大脑兴奋性很重要。

Over the next five years, my research group will investigate how the tissue matrix that surrounds the cells of the brain regulate its activity. We will focus on extracellular matrix components called perineuronal nets (PNNs) to determine their influence on the activity of local neuronal networks in regions of the cortex important for cognitive behaviours (thought processes, attention, memory) and sensory perception. Notably, PNNs regulate the ability of the brain to appropriately wire itself during development. Recent work from our lab suggests that PNNs are reduced in cortex that is repairing itself after a focal injury, suggesting a reduction of PNNs may help the brain rewire. However, PNNs also protect neurons from damage and postmortem studies have shown that they are reduced in the cortex of individuals with schizophrenia. We have recently demonstrated that a loss of PNNs occurs in the cortex of rats in a model of schizophrenia. Moreover, we have directly shown that digestions of PNNs in the cortex leads to cognitive impairment. As such, there is a clear relationship between PNN integrity and the function of the cortex, but little is known about how changes in PNNs affect the activity of neurons. Interestingly, the majority of PNNs in the cortex are associated with “inhibitory” neurons important for reducing brain excitability.