Optogenetic Stimulation in a Model of the Auditory Brainstem Implant

听觉脑干植入模型中的光遗传学刺激

• 批准号: 9077050
• 负责人: Ariel Edward Hight
• 金额: $ 3.11万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9077050
• 关键词: Acoustic Stimulation; Acoustics; Acute; Address; Auditory; Auditory Brain Stem Implants; Behavior; Behavioral; Brain Stem; Bypass; Cell Nucleus; Cells; Characteristics; Chronic; Cochlea; Cochlear Implants; Cochlear nucleus; Collimator; Comprehension; Cues; Detection; Devices; Electric Stimulation; Electricity; Electrodes; Esthesia; Frequencies; Gene Transfer; Goals; Hearing; Hearing Impaired Persons; Implant; Individual; Lasers; Light; Location; Maps; Measures; Modeling; Modification; Morphology; Mus; Nerve Fibers; Neurons; Optics; Ouabain; Outcome; Pathway interactions; Patients; Pattern; Perception; Performance; Pharmaceutical Preparations; Photophobia; Physiologic pulse; Physiological; Population; Positioning Attribute; Preparation; Process; Prosthesis; Pulse Rates; Resolution; Role; Source; Speech; Stimulus; Structure; Surface; Techniques; Testing; Tissues; Training; Transgenic Organisms; Translating; Width; auditory pathway; awake; base; behavioral response; cell type; deafness; design; excitatory neuron; implantable device; improved; indexing; inhibitory neuron; neuroprosthesis; new technology; optical fiber; optogenetics; prevent; public health relevance; relating to nervous system; research study; response; round window; sound; spiral ganglion; success

 DESCRIPTION (provided by applicant): The auditory brainstem implant (ABI) is a neuroprosthesis that restores hearing sensations for deaf people who cannot benefit from a cochlear implant (CI). This implantable device exists of a paddle-style electrode array with electrode contacts along its surface and is placed on the smooth cochlear nucleus (CN) surface of the auditory brainstem. Individual electrodes stimulate the CN to provide frequency/spectral cues and temporal cues to convey multiple features of speech. ABI users typically have speech comprehension performance that is poorer than normal hearing individuals and poorer than users of the cochlear implant, another auditory prosthesis that stimulates the nerve fibers of the cochlea. Two types of information provided in limited degrees by the ABI that are correlated with hearing outcomes are spectral cues and temporal cues. Furthermore, the ABI has the added challenge of delivering these cues to the CN, which contains a number of excitatory and inhibitory neurons that are stimulated indiscriminately by the device. To address the limited success of electrical stimulation in the ABI, we propose an alternative mode of stimulation, one that was recently discovered (Boyden 2005) and is now being used by neuroscientists around the world: optogenetics. Compared to electrical stimulation, optogenetic stimulation uses light to stimulate neurons that have been specifically targeted via gene transfer. As light may be more focused than electrical stimulation, optogenetic stimulation may improve spectral and temporal cues. Additionally, as sensitivity to light may be specifically targeted in a select group of cell types, optogenetic stimulation provides a clear means for dealing with the cellular complexity of stimulated tissue in an ABI model. In this proposed project, we apply optogenetic stimulation in a model for ABI that we have recently established in the mouse. Using acute experiments that record the evoked neural activity, we will determine whether optogenetics improves spectral and temporal cues (Aim 1), and provides a means to bypass the cellular complexity of the CN (Aim 2). Furthermore, since ultimately we want to test whether optogenetic stimulation can provide the same or better information than electrical stimulation, we will compare optogenetic stimulation with electrical and the acoustic stimulation used in natural hearing. While acute studies can address fundamental questions of neurostimulation, it remains elusive whether specific patterns of evoked neural activity translate to perceptual advantages. We will apply the studies of Aims 1 and 2 to direct a behavior experiment measuring the perceptual saliency of optical stimulation (Aim 3). These experiments will determine whether mice are able to hear different stimulations provided by optical stimulation and to compare that with perceptions provided by electrical or acoustic stimulation.

 描述（由适用提供）：听觉的脑干植入物（ABI）是一种神经假体，可恢复无法从人工耳蜗（CI）中受益的聋哑人的听力感觉。该植入器设备存在于桨式电极阵列沿其表面，并放置在听觉脑干的平滑耳蜗核（CN）表面上。单个电极刺激CN，以提供频率/光谱提示和临时提示，以传达多个语音特征。 ABI用户通常的语音理解性能比正常的听力个体差，并且比耳蜗植入物的用户差，这是另一个刺激耳蜗神经纤维的听觉假体。与听力结果相关的ABI以有限程度提供的两种类型的信息是光谱提示和临时提示。此外，ABI还有将这些线索传递到CN的额外挑战，其中包含许多兴奋和抑制性神经元，这些神经元被设备不分青睐。为了解决ABI中电刺激成功的有限成功，我们提出了一种替代的刺激方式，该模式最近被发现（Boyden 2005），现在正在世界各地的神经科学家使用：光遗传学。与电刺激相比，光遗传学刺激使用光刺激通过基因转移特异性靶向的神经元。由于光线可能比电刺激更集中，因此光遗传刺激可以改善光谱和临时提示。此外，由于对光的敏感性可能是针对一组细胞类型的特异性靶向的，因此光遗传学刺激为处理ABI模型中刺激组织的细胞复杂性提供了一种清晰的手段。在这个提出的项目中，我们在记录诱发神经活动的急性实验中应用光遗传刺激，我们将确定光遗传学是否改善了光谱和临时提示（AIM 1），并提供了绕过CN的细胞复杂性的手段（AIM 2）。此外，由于最终我们要测试光遗传刺激是否可以提供比电刺激相同或更好的信息，因此我们将将光遗传学刺激与自然听力中使用的电气刺激和声刺激进行比较。尽管急性研究可以解决神经刺激的基本问题，但仍然难以捉摸的神经活动的特定模式转化为感知优势。我们将应用目标1和2的研究来指导一项行为实验，以测量光学刺激的感知显着性（AIM 3）。这些实验将确定小鼠是否能够听到光学刺激提供的不同刺激，并将其与电或声刺激所提供的感知进行比较。