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: 8397758
• 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 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8397758
• 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. PUBLIC HEALTH RELEVANCE: Cross-modal reorganization of sensory cortex determines the success rate of neuroprosthetic treatments for individuals who are born without, or lose a sense. Given that neuroprosthetics (such as cochlear implants) are unsuccessful in those with extensive cross-modal reorganization, the mechanism behind this plasticity must be understood. By improving our understanding of this type of plasticity, we can explore the possibility of overcoming this obstacle in helping people re-gain sensory experience.

描述（由申请人提供）：一种感觉形态的丧失通常会导致其他感官功能的增强；这种现象被称为跨模态可塑性。特别是视力的丧失会导致盲人的触觉灵敏度、音高辨别能力和声音定位能力的提高。这种增强也可以很快发生，仅仅几天的蒙眼体验就可以改善视力正常的人的盲文阅读。这些跨模态变化与视觉皮层处理剩余感官的功能补充有关。虽然这对那些受影响的人是有益的，但它可能会阻碍恢复失去的感觉的治疗干预。例如，早期失聪患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够有效地处理听觉刺激。我们的实验室报告说，剥夺啮齿动物的视力会改变