DEVELOPMENT OF A 3-DIMENSIONAL ATLAS OF THE GERBIL BRAIN

沙鼠大脑三维图谱的开发

• 批准号: 8171613
• 负责人: DOUGLAS C FITZPATRICK
• 金额: $ 0.55万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8171613
• 关键词: 3-Dimensional; Address; Animals; Applications Grants; Area; Atlases; Auditory; Auditory area; Auditory system; Base of the Brain; Brain; Brain imaging; Cell Nucleus; Chiroptera; Cochlear Implants; Complex; Computer Retrieval of Information on Scientific Projects Database; Data; Development; Disease; Employee Strikes; Funding; Geniculate body structure; Gerbils; Grant; Hearing Impaired Persons; Image; Inferior Colliculus; Institution; Laboratories; Letters; Magnetic Resonance Imaging; Maintenance; Maps; Medial; Methods; Midbrain structure; National Institute on Deafness and Other Communication Disorders; Neuraxis; Output; Pathway interactions; Patients; Pattern; Physiological; Play; Property; Prosencephalon; Research; Research Personnel; Resolution; Resources; Role; Source; Speech; Stimulus; Structure; Surface; Techniques; Thalamic structure; Tinnitus; United States National Institutes of Health; Work; Writing; auditory pathway; base; design; receptor; reconstruction; response; sensory cortex; sensory system; 3-Dimensional; Address; Animals; Applications Grants; Area; Atlases; Auditory; Auditory area; Auditory system; Base of the Brain; Brain; Brain imaging; Cell Nucleus; Chiroptera; Cochlear Implants; Complex; Computer Retrieval of Information on Scientific Projects Database; Data; Development; Disease; Employee Strikes; Funding; Geniculate body structure; Gerbils; Grant; Hearing Impaired Persons; Image; Inferior Colliculus; Institution; Laboratories; Letters; Magnetic Resonance Imaging; Maintenance; Maps; Medial; Methods; Midbrain structure; National Institute on Deafness and Other Communication Disorders; Neuraxis; Output; Pathway interactions; Patients; Pattern; Physiological; Play; Property; Prosencephalon; Research; Research Personnel; Resolution; Resources; Role; Source; Speech; Stimulus; Structure; Surface; Techniques; Thalamic structure; Tinnitus; United States National Institutes of Health; Work; Writing; auditory pathway; base; design; receptor; reconstruction; response; sensory cortex; sensory system

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. GA Johnson wrote a letter of support for their proposal: We submitted an R01 grant application to the National Institute on Deafness and Other Communication Disorders. The project is an integral part of our three specific aims as follow: We propose three specific aims that are designed to address the functional organization of the auditory thalamus, the least understood of the auditory structures in the central nervous system. A fundamental organizing principle of mammalian sensory systems is that features of the stimulus are mapped systematically from the receptor surface to the sensory cortex. In the auditory system, striking transformations in the representations of the stimulus occur between the auditory midbrain (inferior colliculus) and the auditory cortex. One of the most obvious is a reorganization from a single tonotopic representation in the central nucleus of the inferior colliculus (ICc) to multiple tonotopic areas in the auditory cortex. Two general hypotheses suggest how this occurs: 1) There is maintenance of a single tonotopic representation in the auditory thalamus with subsequent multiplication of tonotopic areas in the auditory cortex, or 2) There is a creation of multiple tonotopic areas in the thalamus and maintenance or elaboration of this increase in the cortical projections. Presently, the perceived understanding seems to be that the multiplication of areas is a cortical rather than a thalamic feature, i.e., hypothesis 1 is favored (e.g., Winer and Schreiner, 2005). However, recent results from our laboratories (as well as some results from other laboratories) favor hypothesis 2. Studies in the Fitzpatrick laboratory demonstrated that the mustached bat auditory thalamus contains multiple tonotopically organized areas, similar to the cortical pattern. This complexity at the thalamic level arises from remixing the tonotopic outputs from the ICc. Studies in the gerbil in the Cant laboratory demonstrated at least two topographically organized pathways arising in the central nucleus of the inferior colliculus and terminating in different parts of the ventral division of the medial geniculate nucleus (Cant and Benson, 2006, 2007). Based on these results, the hypothesis guiding this proposal is that the auditory thalamus contains multiple tonotopic areas supported by complex inputs from the ICc. To address this hypothesis, we propose to combine physiological mapping techniques with both imaging and brain alignment techniques and also anatomical mapping of connections between the ICc, auditory thalamus and auditory cortex. Understanding the transformations that occur in auditory representations in the forebrain auditory pathways will be important for designs of speech processors and for selecting targets for direct brain stimulation in deaf patients who cannot use a cochlear prosthesis or in intractable disorders such as tinnitus. Specific Aim 1. To map physiological response properties in the auditory thalamus. The medial geniculate nucleus will be physiologically mapped at high resolution in the gerbil. The organization of the inferior colliculus in the gerbil follows the typical mammalian plan with the central nucleus containing what appears to be a single tonotopic representation of the stimulus. Multiple tonotopic areas are know to exist in the cortex of this species (Budinger et al., 2000). Our hypothesis is that the auditory thalamus also contains multiple tonotopic representations. Each representation would be expected to play a different functional role in audition. All data will be mapped into the three-dimensional MRI-based atlas developed in Specific Aim 3. Specific Aim 2. To use tracing methods to determine the neuroanatomical basis for multiple tonotopically organized areas in the thalamus. Our hypothesis is that it is complexity in the outputs from the ICc leads to creation of multiple tonotopic areas in the thalamus, and that this complexity is then maintained or amplified in projections to the cortical level. To address this hypothesis, we will perform anatomical tracing studies in the same animals used for physiological mapping, and combine the information across animals in the MRI-based brain atlas developed in Specific Aim 3. Specific Aim 3. To use magnetic resonance imaging and brain alignment techniques to develop a three-dimensional atlas of the gerbil midbrain and thalamus that can be used for mapping the physiological and neuroanatomical data. The auditory thalamus presents a special challenge for mapping due to its complex internal organization. Indeed, our working hypothesis is that the ventral division of the medial geniculate nucleus is considerably more complex than currently understood. To provide a convincing demonstration of this complexity, we propose to use high-resolution (80 um voxel size) MRI imaging of the gerbil brain to create a three-dimensional brain reconstruction in which all physiological and anatomical data can be plotted.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 Ga Johnson为他们的建议写了一封支持信： 我们向美国国家耳聋和其他沟通障碍提交了R01赠款申请。该项目是我们三个特定目的不可或缺的一部分，如下： 我们提出了三个旨在解决听觉丘脑功能组织的特定目标，这是对中枢神经系统中听觉结构的理解。哺乳动物感觉系统的基本组织原理是，刺激的特征是从受体表面系统地映射到感觉皮层的。 在听觉系统中，刺激表示中的惊人转换发生在听觉中脑（下丘）和听觉皮层之间。最明显的之一是从下丘中心核（ICC）中的单个吨位表示重组，再到听觉皮层的多个吨位区域。两个一般的假设表明了如何发生这种情况：1）在听觉丘脑中维持单个吨位表示，随后在听觉皮层中进行了吨位的吨位区域的乘法，或2）在丘脑中会产生多个吨位的区域，并在丘脑构图中增加或阐述这种皮质射击。目前，人们认为的理解似乎是区域的繁殖是一种皮质而不是丘脑特征，即假设1受到​​青睐（例如Winer and Schreiner，2005年）。但是，我们的实验室的最新结果（以及其他实验室的一些结果）赞成假设2。在菲茨帕特里克实验室中的研究表明，胡子蝙蝠听觉的丘脑包含多个构图组织的区域，类似于皮质模式。丘脑水平的这种复杂性是由于从ICC中重新混合了Tonotopic输出。在cant实验室中的沙鼠研究表明，在下丘中心核中至少出现了两个地形组织的途径，并终止于内侧基因核的腹侧分裂的不同部分（Cant and Benson，2006，2007）。基于这些结果，指导该建议的假设是听觉丘脑包含由ICC复杂输入支持的多个吨位区域。为了解决这一假设，我们建议将生理映射技术与成像和大脑对齐技术以及ICC，听觉丘脑和听觉皮层之间连接的解剖图相结合。了解前脑听觉途径中听觉表示中发生的转化对于语音处理器的设计以及选择无法使用人工耳蜗假体或棘手疾病（例如耳鸣）的聋患者的直接脑刺激目标很重要。 特定目的1。绘制听觉丘脑中的生理反应特性。内侧基因核将在生理上以高分辨率在Gerbil的高分辨率上进行映射。沙鼠中下丘的组织遵循典型的哺乳动物计划，中央核包含刺激的单个吨位表示。知道该物种的皮质中存在多个吨位区域（Budinger等，2000）。我们的假设是听觉丘脑还包含多个吨位表示。预计每个表示在试镜中都起着不同的功能作用。所有数据将映射到特定目标3中开发的基于三维MRI的地图集。 具体目的2。使用示踪方法来确定丘脑中多个单位组织区域的神经解剖学基础。我们的假设是，从ICC的输出中，丘脑中产生了多个吨位的区域是复杂性，然后在投影到皮质水平的投影中保持或放大了这种复杂性。为了解决这一假设，我们将对用于生理映射的相同动物进行解剖学追踪研究，并将基于MRI的大脑大脑图集中动物的信息结合在一起，在特定目标3中开发。 特定目的3。使用磁共振成像和大脑对准技术来开发沙鼠中脑和丘脑的三维地图集，可用于绘制生理和神经解剖学数据。听觉丘脑由于其复杂的内部组织而提出了映射的特殊挑战。实际上，我们的工作假设是内侧基因核的腹侧分裂比目前所理解的要复杂得多。为了提供这种复杂性的令人信服的演示，我们建议使用沙鼠大脑的高分辨率（80 UM Voxel尺寸）MRI成像，以创建三维脑重建，其中所有生理和解剖学数据都可以绘制。