Axonal myelination of interneurons in cortex: functional significance and plasticity

皮质中间神经元轴突髓鞘形成的功能意义和可塑性 有髓纤维中脉冲传导的速度和效率显然是组成 人类神经系统的密度和功能。也有越来越多的证据表明， 髓鞘形成可以对局部大脑回路的功能产生深远的影响，包括神经元的同步性。 神经振荡器的活动和相互作用。髓磷脂最常被认为与 长轴突投射神经元的突起。但最近，我们发现，局部投射， 相对较短的轴突抑制中间神经元是皮质灰质内有髓轴突的主要来源， 与白质中几乎完全在长距离投射的轴突上形成的髓鞘形成对比 兴奋性神经元。特别是，神经元间髓鞘似乎仅限于含有 蛋白质小白蛋白。 突触抑制是神经元网络的中心特征。在大脑皮层，多种类型的抑制性物质 中间神经元参与调节兴奋性/抑制性平衡，参与神经元同步化和皮质 节奏的产生，以及与经验和学习相关的可塑性。即使轴突髓鞘形成 定义了神经元传递的关键属性，但尚未在皮质中间神经元中进行专门研究。 此外，皮质抑制回路和髓鞘的病理都与许多 神经和精神障碍，包括多发性硬化症、精神分裂症和自闭症。我们的现在 关于皮质灰质的髓鞘形成，特别是抑制轴突的髓鞘形成的知识， 如果我们要克服这种破坏性的疾病，就必须加以加强。 这项建议是基于电生理学和阵列断层扫描的新组合，它提供了 单个神经元或成对突触连接神经元的功能、结构和分子数据。这个 该项目将首先研究小白蛋白阳性篮子细胞的有髓轴突，并将它们之间的相互关系 结构组成和分子组成及其作用的电生理性质 电位放电和由此产生的突触传递到目标锥体神经元。一旦这样的基线 已经证实，小白蛋白中间神经元的轴突髓鞘形成对神经元的可塑性有贡献。 神经元回路将以桶状皮质感觉剥夺为模型进行评估。该项目将结束 对多发性硬化症小鼠模型神经元间髓鞘形成的病理变化进行了研究。 这项提议将提供关于皮质中间神经元髓鞘组织的急需数据 这个组织的功能后果和可塑性，以及它在多发性硬化症中的潜在作用。

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.