Axonal myelination of interneurons in cortex: functional significance and plasticity

皮质中间神经元的轴突髓鞘形成：功能意义和可塑性

基本信息

批准号：
9173829
负责人：
Vernon Daniel MADISON
金额：
$ 34.6万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-07-15 至 2021-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9173829
关键词：
4-Aminobutyrate aminotransferase Action Potentials Affect Anatomy Animals Area Array tomography Autistic Disorder Axon Brain Cerebral cortex Cerebrum Characteristics Cognitive Cortical Synchronization Data Demyelinating Diseases Developmental Course Disease Electrophysiology (science)Equilibrium Experimental Autoimmune Encephalomyelitis Fiber Generations Human Individual Interneurons Investigation Ion Channel Knowledge Learning Length Measurement Mental disorders Modeling Modification Molecular Multiple Sclerosis Mus Myelin Myoepithelial cell Nervous system structure Neurons Parvalbumins Pathology Pattern Pharmaceutical Preparations Pharmacotherapy Physiological Play Process Property Proteins Published Comment Role Schizophrenia Sensory Deprivation Source Speed Stimulus Synapses Synaptic Transmission Thick Time Vigabatrin barrel cortex base cell type density excitatory neuron experience gamma-Aminobutyric Acid gray matter hippocampal pyramidal neuron information processing inhibitor/antagonist mouse model myelination nervous system disorder neural circuit neuronal circuitry neurotransmission novel physical property postsynaptic neurons relating to nervous system response somatosensory synaptic inhibition white matter

项目摘要

Axonal myelination of interneurons in cortex: functional significance and plasticity The speed and efficiency of impulse conduction in myelinated fibers is clearly fundamental to component density and functional powers of the human nervous system. There is also growing evidence that changes in myelination can have profound effects on the function of local brain circuits, including synchrony of neuronal activity and the interaction of neural oscillators. Myelin is most often thought of in association with the processes of long-axon projection neurons. But recently, we have discovered that the locally-projecting, relatively short-axon inhibitory interneurons are a major source of myelinated axons within cortical gray matter, in contrast to the myelin in white matter that forms almost exclusively on the axons of long-distance projecting excitatory neurons. In particular, interneuronal myelin appears to be confined to interneurons containing the protein parvalbumin. Synaptic inhibition is a central feature of neuronal networks. In cortex, numerous types of inhibitory interneurons participate in regulating the excitatory/inhibitory balance, in neuronal synchronization and cortical rhythms generation, and in plasticity associated with experience and learning. Even though axonal myelination defines crucial properties of neuronal transmission, it has not been specifically studied in cortical interneurons. Furthermore, pathologies of both the cortical inhibitory circuitry and of myelin are associated with many neurological and mental disorders, including multiple sclerosis, schizophrenia, and autism. Our present knowledge of myelination in the cortical gray matter, and in particular the myelination of inhibitory axons, is limited and certainly must be augmented if we are to conquer such devastating disorders. This proposal is based on a novel combination of electrophysiology and array tomography that delivers functional, structural and molecular data on individual neurons or pairs of synaptically connected neurons. The project will begin by investigating myelinated axons of parvalbumin positive basket cells and correlating their structural organization and molecular composition with the electrophysiological properties of their action potential discharge and resulting synaptic transmission onto target pyramidal neurons. Once such a baseline has been established, the contribution of axonal myelination of parvalbumin interneurons to the plasticity of neuronal circuits will be assessed using barrel cortex sensory deprivation as a model. The project will conclude with a study of the pathological changes of interneuronal myelination in a mouse model of multiple sclerosis. This proposal will provide much needed data regarding the organization of myelin of cortical interneurons, the functional consequences and the plasticity of this organization, and its potential role in multiple sclerosis.

皮层中间神经元的轴突髓鞘化：功能意义和可塑性髓鞘纤维中脉冲传导的速度和效率显然是成分的基础人类神经系统的密度和功能能力。越来越多的证据表明髓鞘化可能会对局部脑电路的功能产生深远影响，包括神经元的同步活性和神经振荡器的相互作用。髓鞘最常被认为与长轴投影神经元的过程。但是最近，我们发现本地项目，相对较短的抑制性中间神经元是皮质灰质中髓鞘轴突的主要来源，与白质中的髓磷脂相反，几乎完全在长距离投影的轴突上形成兴奋性神经元。特别是，神经元髓磷脂似乎仅限于包含的中间神经元蛋白质白蛋白。突触抑制是神经元网络的主要特征。在皮层中，多种类型的抑制作用中间神经元参与调节兴奋性/抑制平衡，神经元同步和皮质节奏产生，以及与经验和学习相关的可塑性。即使轴突髓鞘定义了神经元传播的关键特性，在皮质中间神经元中尚未专门研究它。此外，皮质抑制回路和髓磷脂的病理学都与许多神经和精神障碍，包括多发性硬化症，精神分裂症和自闭症。我们的礼物对皮质灰质的髓鞘形成的了解，尤其是抑制性轴突的髓鞘形成是如果我们要征服这种毁灭性的疾病，则有限，当然必须增加。该建议基于电生理学和阵列断层扫描的新型组合在单个神经元或成对的突触连接神经元的功能，结构和分子数据。这项目将首先调查白蛋白蛋白阳性篮细胞的髓鞘轴突并将其关联其作用的电生理特性的结构组织和分子组成潜在的放电和导致的突触传播到靶锥体神经元。一旦这样的基线已经建立了白细胞蛋白中间神经元的轴突髓鞘形成对可塑性的贡献神经元电路将以桶状皮质感觉剥夺作为模型进行评估。该项目将得出结论通过研究多发性硬化症的小鼠模型中神经元髓鞘的病理变化。该建议将提供有关皮质中间神经元髓鞘组织的急需数据，功能后果和该组织的可塑性及其在多发性硬化症中的潜在作用。