Long-term plasticity expressed in layer 2/3 cortical microcircuits

2/3 层皮质微电路表达的长期可塑性

• 批准号: 9223754
• 负责人: Hyungbae Kwon
• 金额: $ 47.75万
• 依托单位: MAX PLANCK FLORIDA CORPORATION
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-05-18 至 2020-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9223754
• 关键词: Action Potentials; Address; Animals; Area; Autistic Disorder; Brain; Brain Diseases; Brain Injuries; Cells; Characteristics; Code; Complex; Cortical Column; Development; Disease; Disinhibition; Electrophysiology (science); Elements; Epilepsy; Foundations; Functional disorder; Glutamates; Goals; Image; Individual; Laboratories; Lead; Learning; Mediating; Mental disorders; Methods; Modification; Molecular; Monitor; Morphology; Neurons; Optics; Pathogenesis; Pattern; Population; Process; Resolution; Rodent; Schizophrenia; Sensory; Somatosensory Cortex; Structure; Study models; Symptoms; Synapses; Techniques; Testing; Time; Training; Transgenic Animals; Vertebral column; Vibrissae; Work; awake; barrel cortex; cell type; design; excitatory neuron; hippocampal pyramidal neuron; improved functioning; in vivo; insight; nervous system disorder; neural circuit; neuronal excitability; neuropsychiatric disorder; novel; novel strategies; optogenetics; photolysis; public health relevance; relating to nervous system; restoration; sensory cortex; spatiotemporal; two-photon

 DESCRIPTION (provided by applicant): Normal brain function requires proper neuronal connections. Layer 2/3 cortical pyramidal neurons in a mammalian brain have similar morphological and functional characteristics, but they tend to form functionally distinct microcircuits by making specialized connections. The cellular and molecular mechanisms by which one neuron finds specific target neurons and eventually forms functional subnetworks are not fully understood. A growing body of evidence indicates that the functional microcircuit formation is largely influenced by the activity pattern arising in local circuits. Presumably, the exact timing of action potential firing, the degree of excitability, and the level of inhibition ar important, but how these factors are operated together and are expressed at the level of multiple neurons have not yet been precisely defined. We propose to address these questions by using electrophysiological and optical approaches to visualize and manipulate neuronal activities at individual cell level. In the Aim 1, we seek to determine how spikes generated in multiple neurons within a short time window influence circuit reorganization by varying three factors: spike timing and number, distance between neurons, and the number of neurons. In Aim 2, cellular mechanisms such as neuronal excitability and the involvement of disinhibition will be examined. Lastly, Aim 3 is designed to test whether circuit assembly can be manipulated in awake behaving animals. Completion of the proposed work will provide mechanistic insight during cortical circuit plasticity and would establish experimental evidence for non-random features of neural connectivity in the mammalian brain. Abnormal neuronal connectivity has been implicated in various neuropsychiatric diseases such as schizophrenia, epilepsy, and autism spectrum diseases, and can directly influence the symptoms of other brain disorders or injuries. Thus, understanding cellular mechanisms of activity-dependent redistribution of local circuits could also help inform the development of novel strategies for circuit dysfunction.

 描述（由申请人提供）：正常的大脑功能需要适当的神经元连接。哺乳动物大脑中的第 2/3 层皮质锥体神经元具有相似的形态和功能特征，但它们倾向于通过建立专门的连接来形成功能不同的微电路。一个神经元找到特定目标神经元并最终形成功能子网络的细胞和分子机制尚不完全清楚。越来越多的证据表明，功能性微电路的形成在很大程度上受到局部电路中出现的活动模式的影响。据推测，动作电位放电的确切时间、兴奋程度和抑制水平很重要，但这些因素如何一起运作并在多个神经元水平上表达尚未得到精确定义。我们建议通过使用电生理学和光学方法在个体细胞水平上可视化和操纵神经元活动来解决这些问题。在目标 1 中，我们试图通过改变三个因素来确定短时间窗口内多个神经元产生的尖峰如何影响电路重组：尖峰时间和数量、神经元之间的距离以及神经元的数量。在目标 2 中，将检查神经元兴奋性和去抑制的参与等细胞机制。最后，Aim 3 旨在测试电路组件是否可以在清醒的动物身上进行操作。完成拟议的工作将为皮层回路可塑性提供机制见解，并为哺乳动物大脑中神经连接的非随机特征建立实验证据。神经元连接异常与各种神经精神疾病有关，例如精神分裂症、癫痫和自闭症谱系疾病，并且可以直接影响其他脑部疾病或损伤的症状。因此，了解局部回路活动依赖性重新分布的细胞机制也有助于为回路功能障碍的新策略的开发提供信息。