Influence of Perineuronal nets on cortical neurons

神经周围网对皮质神经元的影响

• 批准号: 9897604
• 负责人: JOSHUA Craig BRUMBERG
• 金额: $ 11.55万
• 依托单位: QUEENS COLLEGE
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-05-01 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9897604
• 关键词: Action Potentials; Alteplase; Asses; Behavior; Biochemical; Biological Assay; Brain; Cell surface; Cells; Cytoskeleton; Data; Development; Environment; Enzymes; Extracellular Matrix; Human; Immunochemistry; In Vitro; Incubators; Interneurons; Laboratories; Lead; Link; Mediating; Membrane Potentials; Microglia; Mus; Neonatal; Neuroglia; Neurons; Parvalbumins; Pharmacology; Physiological; Physiology; Play; Process; Property; Public Health; Resistance; Rest; Role; Sensory; Sensory Deprivation; Slice; Somatosensory Cortex; Structure; Synapses; Synaptic plasticity; Techniques; Testing; Thalamic structure; Time; Tissues; Vibrissae; Visual system structure; Whole-Cell Recordings; barrel cortex; cognitive process; critical developmental period; deprivation; excitatory neuron; experience; inhibitory neuron; insight; knockout animal; man; mouse model; neocortical; neural circuit; neuron development; novel; patch clamp; preservation; receptive field; relating to nervous system

Abstract Sensory deprivation from mice to man has been shown to have profound impacts on neuronal physiology, behavior and cognitive processes. Underling these changes are alterations in neuronal and non-neuronal structures. Our preliminary data shows that following one month of whisker trimming induced sensory deprivation the perineuronal net (PN), a neuron specific form of the extra cellular matrix, is significantly reduced in the barrel cortex of mice. The loss of the PN is most prominent around fast-spiking parvalbumin positive GABAergic interneurons. Converging evidence has shown that fast-spiking interneurons play a pivotal role in the closure of the developmental critical period in the visual system and their proper functioning is necessary for the proper physiological functioning of the cortex. Coincident with deprivation induced decreases in the PN we observed increases in the enzyme tissue plasminogen activator (tPA) which dissolves the PN. Under the same conditions microglia become activated, thus we propose that sensory deprivation induces microglia activation which release tPA and thus decrease the PN. In Aim 1 we will demonstrate a causal link between sensory deprivation, microglia activation and tPA release resulting in PN decreases using immunocytochemical techniques in conjunction with stereology. In Aim 2 we will focus on the physiological roll PNs have in modifying the intrinsic and synaptic properties of fast-spiking interneurons. We will employ our novel small volume incubator which allows for time dependent degradation of the PN in conjunction with dual whole-cell recordings.

抽象的 已经证明，从小鼠到人的感觉剥夺对神经元有深远的影响 生理，行为和认知过程。这些变化的基础是改变 神经元和非神经元结构。我们的初步数据表明，在一个月之后 晶须修剪诱导的感觉剥夺是神经元网（PN），一种神经元特异性形式 在小鼠的枪管皮层中，额外的细胞基质的量显着降低。损失 PN在快速刺激性的白蛋白阳性GABA能中间神经元中最突出。 融合的证据表明，快速加快的中间神经元在闭合中起关键作用 视觉系统中的发育关键时期及其适当的功能是 对于皮质的适当生理功能所必需的。与剥夺一致 诱导的PN降低，我们观察到酶组织的增加 溶解PN的激活剂（TPA）。在相同条件下，小胶质细胞被激活， 因此，我们提出感觉剥夺会诱导小胶质细胞激活，从而释放TPA和 因此减少了PN。在AIM 1中，我们将展示感觉剥夺之间的因果关系， 小胶质细胞激活和TPA释放，导致PN使用免疫细胞化学降低 技术与立体学结合。在AIM 2中，我们将专注于生理卷PN 在修改快速刺激性中间神经元的固有和突触特性时具有。我们将 采用我们新颖的小体积孵化器，允许时间依赖于时间的降解 PN与双重全细胞记录结合使用。