Mesh electronics for understanding space encoding in the amphibian brain

项目总结/摘要 许多动物依靠空间认知来进行日常生存，以便识别熟悉的地方和处理动作 通过或在位置之间。海马中的各种空间编码细胞对空间行为非常重要 在哺乳动物中。然而，空间的神经编码在其他脊椎动物类群中仍然没有特征，包括 两栖动物，其简单的大脑结构表明编码空间的替代机制。在我们的严重差距 对简单的两栖动物大脑功能的理解，部分源于记录神经活动的困难。 两栖动物的大脑比其他脊椎动物在头骨内表现出更大程度的运动， 涉及使用常规可植入神经探针在运动动物中进行电生理学记录的不稳定性。 最近，我们的实验室开发了1）一种新形式的电子产品，具有组织般的灵活性和可拉伸性， 长期稳定的神经记录与单神经元分辨率，和2）甘蔗蟾蜍作为模型，以研究神经 两栖动物空间行为的基础。我们建议开发可拉伸网状电子神经探针， 内侧软腭单个神经元的电生理记录， 海马体，在自由移动的蟾蜍中。我们假设内侧软腭包含的神经元， 特异性，类似于哺乳动物海马中的定位细胞或头部方向细胞，但分辨率较低， 与特定环境特征的高度相关性（例如，边界）。我们预测，一些细胞的单细胞活性 在自由移动的蟾蜍中，通过网状电子设备测量的内侧腭中的神经元将与 在行为竞技场内的空间位置，而从另一个区域记录的神经元则不会。在记录之前 从内侧腭板，我们将建立网状记录在视顶盖，一个地区很容易达到的背 这是以前电生理学研究的目标。我们将验证结果， 神经记录数据与脑切片免疫组织学成像的严格统计分析和比较。 了解两栖动物如何学习和编码空间信息将揭示另一种机制， 空间经验的学习和编码，或者哪种范式是脊椎动物大脑功能的祖先特征 以及空间编码的神经生物学原理如何在脊椎动物分类群中推广。重要的是，我们的方法 这将导致在头骨大幅度运动的大脑中开发长期稳定的记录技术。 这一进展将是一个有价值的研究工具，扩大电生理学研究的范围和可能性， 其他动物。该项目的成功完成将使我们能够获得原理证明数据， 神经解剖学与神经功能相关的基本问题，这对R 01未来的应用至关重要。 此外，在甘蔗蟾蜍中建立一个记录协议将允许神经功能的其他方面， 两栖动物，一个研究领域，迄今为止一直受到限制，由于技术的限制。综上所述，我们的建议 这项研究将有助于阐明相对简单的两栖动物大脑中的核心编码原则，并揭示这些编码原则是如何在大脑中产生的。 空间编码的原理可能在脊椎动物分类群中普遍适用。

PROJECT SUMMARY/ABSTRACT Many animals rely on spatial cognition for daily survival in order to recognize familiar places and process movements through or between locations. A variety of space-encoding cells in the hippocampus are important for spatial behaviors in mammals. However, neural encoding of space remains uncharacterized in other vertebrate taxa, including amphibians, whose simpler brain structure suggests alternative mechanisms of encoding space. The severe gap in our understanding of how the simple amphibian brain functions stems, in part, from difficulty in recording neural activity. The amphibian brain exhibits a greater degree of movement within the skull than other vertebrates, which could lead to an instability of electrophysiology recordings in moving animals using conventional implantable neural probes. Recently our labs have developed 1) a new form of electronics with tissue-like flexibility and stretchability for chronically stable neural recording with single-neuron resolution, and 2) cane toads as a model to study the neural basis of amphibian spatial behaviors. We propose to develop stretchable mesh electronic neural probes for in vivo electrophysiological recording of single neurons in the medial pallium, the proposed homolog of the mammalian hippocampus, in freely moving toads. We hypothesize that the medial pallium contains neurons that fire with spatial specificity, similar to place cells or head direction cells in the mammalian hippocampus, but with lower resolution and high correlation with specific environmental features (e.g., borders). We predict that single-cell activity of some neurons in the medial pallium, which is measured by mesh electronics in freely moving toads, will be correlated with spatial position within a behavioral arena, while neurons recorded from another region will not. Prior to recording from the medial pallium, we will establish mesh recordings in the optic tectum, a region easily accessible on the dorsal side of the brain which has been a target for previous electrophysiology studies. We will validate the results with rigorous statistical analyses and comparison of neural recording data with immunohistological imaging of brain slices. Understanding how amphibians learn and encode spatial information will reveal either alternative mechanisms for learning and encoding of spatial experiences or which paradigms are ancestral features of vertebrate brain function and how neurobiological principles of space coding might generalize across vertebrate taxa. Importantly, our approach will result in the development of chronically stable recording techniques in brains with large movements in the skull. This advance will be a valuable research tool for expanding the scope and possibility of electrophysiology studies in other animals. Successful completion of this project will allow us to obtain proof-of-principle data elucidating fundamental questions relating neuroanatomy to neuronal functions, which is crucial for future R01 applications. Furthermore, establishing a recording protocol in cane toads will allow for other aspects of neural function in amphibians, a research area that has thus far been limited due to technological constraints. In summary, our proposed research will help elucidate the core coding principles in the relatively simple amphibian brain and reveal how these principles for spatial encoding might generalize across vertebrate taxa.