Microglial interactions with the Perineuronal Net

摘要 感觉剥夺深刻地影响皮质回路，进而影响生物体 从老鼠到人的功能。传统上，研究的重点是神经元如何响应 发育过程中感觉体验的变化。最近，人们注意到了非 神经元成分，如小胶质细胞和神经周围神经网络(神经元特有的形式 细胞外基质)。小胶质细胞，大脑免疫细胞，改变其形态以响应 修剪胡须会引起感觉丧失，它们的体节增大，突起收缩， 它们处于激活状态的特征。与此相一致的是，神经周神经网络减少。 优先分布在副白蛋白阳性的GABA能中间神经元周围。生理学研究已经 研究表明，这些神经元在调节皮质兴奋性和随之而来的 神经周围神经网络消化后发现其固有的生理特性发生改变 (尖峰概率越低，输入电阻越低)。我们最重要的假设是感官 剥夺激活了小胶质细胞，而小胶质细胞又形成了神经周网络。我们将对此进行调查 动物修剪胡须时耗尽小胶质细胞的因果关系和评估 周围神经网。这种关系的功能后果将用以下方法研究 丘脑皮质脑片全细胞膜片钳记录 将使用基于纹理的新对象范例来分析分支。

Abstract Sensory Deprivation profoundly impacts cortical circuits which in turn impact organismal functioning from mouse to man. Traditionally research has focused on how neurons respond to changes in sensory experience during development. Recently attention has been drawn to non- neuronal elements such as microglia and the perineuronal net (neuron specific form of the extracellular matrix). Microglia, the brains immune cells, alter their morphology in response to whisker trimming evoked sensory deprivation, their somata enlarge and their process retract, hallmarks of their activated state. Coincident with this, the perineuronal net is reduced preferentially around parvalbumin positive GABAergic interneurons. Physiological studies have shown that these neurons play a key role in regulating cortical excitability and following perineuronal net digestion we found their intrinsic physiological properties become altered (lower probability of spiking, lower input resistance). Our overarching hypothesis is that sensory deprivation activates microglia which in turn shape the perineuronal net. We will investigate this causal relationship by depleting microglia while trimming the animal’s whiskers and evaluating the perineuronal net. The functional consequences of this relationship will be studied using whole-cell patch clamp recordings in the thalamocortical slice and finally the behavioral ramifications will be assayed using a texture based novel object paradigm.