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

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

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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.

抽象的感觉剥夺对皮质循环产生深远影响，从而影响生物从鼠标到人的功能。传统研究的重点是神经元如何反应在开发过程中的感觉体验的变化。最近注意到了非神经元元素，例如小胶质细胞和神经元网（神经元特异性形式）细胞外基质）。小胶质细胞，大脑免疫核素，改变了其形态晶须修剪诱发的感觉剥夺，其躯体扩大和过程缩回，其激活状态的标志。与此一致，会内神经元网减少优先围绕白蛋白阳性GABA能中间神经元。生理学研究表明这些神经元在调节皮质刺激和关注方面起着关键作用会阴网络消化我们发现它们的内在物理特性已改变（峰值的概率较低，输入电阻较低）。我们的总体假设是感官剥夺会激活小胶质细胞，从而塑造了周围神经元网。我们将调查此事修剪动物的胡须和评估时，通过耗尽小胶质细胞来耗尽小胶质细胞来因果关系会内神经元网。这种关系的功能后果将使用丘脑皮质切片中的全细胞斑块夹记录，最后是行为分支将使用基于纹理的新对象范式分配。