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.

摘要 从小鼠到人类的感觉剥夺已经被证明对神经元有深远的影响。 生理、行为和认知过程。在这些变化的基础上， 神经元和非神经元结构。我们的初步数据显示，经过一个月的 胡须修剪诱导的感觉剥夺神经元特异性形式的神经元周围网（PN 在小鼠的桶状皮质中，细胞外基质的含量显著降低。的损失 PN是最突出的周围快速尖峰小白蛋白阳性GABA能中间神经元。 越来越多的证据表明，快速发放的中间神经元在闭合过程中起着关键作用。 视觉系统的发育关键期和它们的正常功能， 大脑皮层正常生理功能所必需的与剥夺相一致 我们观察到组织纤溶酶原的增加 活化剂（tPA），溶解PN。在同样的条件下，小胶质细胞被激活， 因此，我们提出感觉剥夺诱导小胶质细胞活化，其释放tPA， 从而降低PN。在目标1中，我们将证明感觉剥夺， 使用免疫细胞化学法检测小胶质细胞活化和tPA释放导致PN减少 技术与立体学相结合。在目标2中，我们将重点关注生理滚动PN 在改变快速尖峰中间神经元的内在和突触特性方面具有重要作用。我们将 采用我们的新型小体积培养箱，其允许时间依赖性降解的 PN结合双全细胞记录。