Mesh electronics for understanding space encoding in the amphibian brain

项目概要/摘要 许多动物依靠空间认知来维持日常生存，以识别熟悉的地方并处理运动 通过地点或地点之间。海马体中的各种空间编码细胞对于空间行为很重要 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，其更简单的大脑结构表明了编码空间的替代机制。我们的严重差距 对简单两栖动物大脑功能的理解部分源于记录神经活动的困难。 与其他脊椎动物相比，两栖动物的大脑在头骨内表现出更大程度的运动，这可能导致 使用传统的植入式神经探针移动动物时电生理学记录的不稳定性。 最近，我们的实验室开发了 1) 一种新型电子产品，具有组织般的灵活性和可拉伸性，可用于 具有单神经元分辨率的长期稳定的神经记录，2）甘蔗蟾蜍作为研究神经元的模型 两栖动物空间行为的基础。我们建议开发用于体内的可拉伸网状电子神经探针 内侧大脑皮层中单个神经元的电生理记录，被认为是哺乳动物的同源物 海马体，在自由移动的蟾蜍身上。我们假设内侧大脑皮层包含与空间相关的神经元 特异性，类似于哺乳动物海马中的位置细胞或头部方向细胞，但分辨率较低， 与特定环境特征（例如边界）高度相关。我们预测一些单细胞活性 内侧大脑皮层中的神经元是通过自由移动的蟾蜍中的网状电子设备测量的，将与 行为领域内的空间位置，而从另一个区域记录的神经元则不会。录音前 从内侧大脑皮层，我们将在视顶盖中建立网状记录，该区域在背侧很容易到达 大脑的一侧，这一直是先前电生理学研究的目标。我们将验证结果 严格的统计分析以及神经记录数据与脑切片免疫组织学成像的比较。 了解两栖动物如何学习和编码空间信息将揭示以下两种替代机制： 空间体验的学习和编码，或者哪些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 将导致在颅骨发生较大运动的大脑中长期稳定的记录技术的发展。 这一进展将成为扩大电生理学研究范围和可能性的宝贵研究工具。 其他动物。该项目的成功完成将使我们能够获得阐明原理的验证数据 有关神经解剖学和神经元功能的基本问题，这对于未来的 R01 应用至关重要。 此外，在甘蔗蟾蜍中建立记录协议将允许在其他方面研究甘蔗蟾蜍的神经功能。 两栖动物，这一研究领域迄今为止由于技术限制而受到限制。综上所述，我们提出的 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理，并揭示这些原理如何 空间编码的原理可能适用于脊椎动物分类单元。

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.