Cross-modal changes in auditory cortex circuitry after visual deprivation

视觉剥夺后听觉皮层电路的跨模式变化

• 批准号: 8489138
• 负责人: Emily Rose Petrus
• 金额: $ 4.22万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-06-01 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8489138
• 关键词: Affect; Area; Auditory; Auditory area; Blindness; Brain; Brain Injuries; Cochlear Implants; Complement; Cytoskeletal Proteins; Data; Discrimination; Equilibrium; Event; Excitatory Synapse; Hearing Impaired Persons; Individual; Inhibitory Synapse; Interneurons; Lead; Measures; Mediating; Modality; Molecular; Mus; Nerve Degeneration; Neurons; Parvalbumins; Play; Process; Proteins; Reading; Recruitment Activity; Regulation; Reporting; Rhodopsin; Rodent; Role; Sensory; Sensory Process; Side; Site; Somatosensory Cortex; Sound Localization; Stimulus; Stroke; Synapses; Synaptic Transmission; Synaptic plasticity; System; Tactile; Testing; Therapeutic Intervention; Transcranial magnetic stimulation; Transgenic Mice; Vision; Visual; Visual Cortex; Visually Impaired Persons; Wild Type Mouse; Work; auditory stimulus; barrel cortex; braille; experience; extrastriate visual cortex; hippocampal pyramidal neuron; improved; inhibitory neuron; mouse model; neural circuit; neural prosthesis; neurotropic; novel; postsynaptic; relating to nervous system; response; sensory cortex; somatosensory; success; visual deprivation

DESCRIPTION (provided by applicant): The loss of one sensory modality often results in functional enhancement of the remaining senses; this phenomenon is called cross-modal plasticity. The loss of vision specifically can result in better tactile acuity, pitch discriminatin and sound localization in blind individuals. This enhancement can also happen quite quickly, only a few days of blindfold experience can lead to improved Braille reading in normally sighted individuals. These cross-modal changes are correlated with functional recruitment of the visual cortex for processing the remaining senses. While this is beneficial to those affected, it may hinder therapeutic interventions to recover the lost sense. For example, the success of cochlear implants for early deaf people is quite low because extensive cortical reorganization no longer can effectively process auditory stimuli. Our lab reported that depriving rodents of vision alters excitatory synaptic transmission in barrel and auditory cortices. However, regulation of excitatory synaptic transmission represents only half the story of how plasticity mechanisms enhance the remaining senses following visual deprivation. The balance of excitation and inhibition are crucial for normal function in any neuronal circuit. For this reason we hypothesize that changes in excitatory synaptic transmission should also be complemented by inhibitory changes. In addition, this study aims to delineate the molecular mechanisms behind excitatory and inhibitory cross-modal plasticity. By using transgenic mouse models targeting specific activity-regulated gene products (i.e. Arc/Arg3.1 KO and BDNF-KIV KI), which show altered plasticity mechanisms and specifically target excitatory and inhibitory synapses, we can identify if these molecules are important for cross-modal reorganization of neural circuits. Finally, using channel rhodopsin activated parvalbumin neurons, we will investigate the role of this set of inhibitory neurons in cross-modal plasticity. Results from this work will directly impact our understanding of how spared sensory modalities become enhanced following the loss of one sense.

描述（由申请人提供）：一种感觉模态的丧失通常会导致其余感觉的功能增强;这种现象称为跨模态可塑性。视力的丧失特别能导致盲人更好的触觉敏锐度、音高辨别力和声音定位。这种增强也可以发生得相当快，只有几天的蒙眼经验可以导致改善盲文阅读在正常视力的个人。这些跨模态的变化与视觉皮层的功能招聘有关，用于处理其余的感觉。虽然这对受影响的人有益，但它可能会阻碍恢复失去的感觉的治疗干预。例如，早期失聪者的人工耳蜗植入成功率很低，因为广泛的皮层重组不再能有效地处理听觉刺激。 我们的实验室报告说，剥夺啮齿动物的视觉， 兴奋性突触传递在桶和听觉皮层。然而，兴奋性突触传递的调节只是可塑性机制如何增强视觉剥夺后剩余感觉的故事的一半。兴奋和抑制的平衡对于任何神经元回路的正常功能都是至关重要的。基于这个原因，我们假设兴奋性突触传递的变化也应该由抑制性变化来补充。此外，本研究旨在阐明兴奋性和抑制性跨模态可塑性背后的分子机制。通过使用转基因小鼠模型针对特定的活性调节的基因产物（即弧/Arg3.1 KO和BDNF-KIV KI），这表明改变可塑性机制，并特别针对兴奋性和抑制性突触，我们可以确定这些分子是否是重要的跨模态重组的神经回路。最后，使用通道视紫红质激活的小清蛋白神经元，我们将调查这组抑制性神经元在跨模态可塑性中的作用。这项工作的结果将直接影响我们对一种感觉丧失后备用感觉方式如何增强的理解。