Mesh electronics for understanding space encoding in the amphibian brain

项目摘要/摘要 许多动物的日常生存依赖于空间认知，以便识别熟悉的位置和处理运动 穿过或在不同地点之间。海马体中的各种空间编码细胞对空间行为很重要 在哺乳动物身上。然而，在其他脊椎动物分类中，空间的神经编码仍然没有特征，包括 两栖动物，其更简单的大脑结构暗示了编码空间的另一种机制。我们之间的严重差距 理解简单的两栖动物大脑是如何运作的，部分原因是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的运动程度，这可能会导致 与使用传统可植入神经探头的运动动物的电生理学记录的不稳定性有关。 最近，我们的实验室开发了一种新形式的电子产品，具有组织一样的柔韧性和伸缩性 用单神经元分辨率进行长期稳定的神经记录；2)以甘蔗蟾蜍为模型研究神经 两栖动物空间行为的基础。我们建议开发可伸展的网状电子神经探针，用于活体 电生理记录大脑皮层内侧的单个神经元，这是哺乳动物的同源物 自由活动的蟾蜍体内的海马体。我们假设内侧大脑皮层含有在空间上放电的神经元。 特异性，类似于哺乳动物海马区的放置细胞或头部定向细胞，但分辨率和 与特定环境特征(例如边界)高度相关。我们预测某些细胞的单细胞活性 内侧大脑皮层的神经元，这是用网状电子学在自由活动的蟾蜍身上测量的，将与 在行为领域内的空间位置，而从另一个区域记录的神经元不会。在录制之前 从大脑皮层内侧，我们将在视顶盖建立网状记录，这是一个在背部很容易到达的区域。 大脑的一侧，这是以前电生理学研究的目标。我们将通过以下方式验证结果 神经记录数据与脑片免疫组织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 空间经验的学习和编码，或者哪些范例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类别中推广。重要的是，我们的方法 这将导致在颅骨有较大运动的大脑中开发出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，以扩大电生理研究的范围和可能性 其他动物。这个项目的成功完成将使我们能够获得原则证明数据，以阐明 与神经解剖学和神经元功能相关的基本问题，这对未来R01的应用至关重要。 此外，在甘蔗蟾蜍中建立记录协议将允许神经功能的其他方面 两栖动物，这是一个研究领域，到目前为止由于技术限制而受到限制。总而言之，我们的建议 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 空间编码的原理可能适用于脊椎动物类群。

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.