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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：
10344171
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/10344171
关键词：
Acute Adopted Adult Anatomy Animals Attention Behavior Behavioral Biological Assay Brain Cells Characteristics Communication Coupled Development Digestion Discrimination Elements Environment Excision Excitatory Postsynaptic Potentials Extracellular Matrix Frequencies Functional disorder Image Analysis Immune Immunohistochemistry Inflammatory Response Injections Interneurons Kinetics Lead Lipopolysaccharides Macrophage Colony-Stimulating Factor Microglia Minocycline Morphology Mus Neuroglia Neurons Organism Parvalbumins Performance Pharmacology 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 base density experience experimental study inhibitor man mouse development nervous system disorder neural circuit neurological pathology neuronal cell body novel patch clamp preservation receptive field relating to nervous system 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