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Microglial interactions with the Perineuronal Net

小胶质细胞与神经周围网络的相互作用

基本信息

批准号：
10634512
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
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-05-01 至 2025-10-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10634512
关键词：
Acute Adopted Adult Anatomy Animals Attention Behavior Behavioral Biological Assay Brain Cells Characteristics Communication Coupled Cytoprotection Development Digestion Discrimination Elements Environment Excision Excitatory Postsynaptic Potentials Extracellular Matrix Frequencies Functional disorder Image Analysis Immune Immunohistochemistry Inflammatory Response Injections Interneurons Kinetics Lipopolysaccharides Macrophage Colony-Stimulating Factor Microglia Minocycline Morphology Mus Neuroglia Neurons Organism Parvalbumins Performance Physiological Play Probability Process Property Public Health Research Resistance Role Sensory Sensory Deprivation Shapes Slice Somatosensory Cortex Stress Structure Synapses Texture Thalamic structure Training Vibrissae Work density experience experimental study inhibitor man mouse development nervous system disorder neural neural circuit neurological pathology novel oxidation patch clamp pharmacologic preservation receptive field response sensory input whisker discrimination

项目摘要

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.

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内在生理特性发生改变 (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。