Examining the integration of inputs by the subiculum during virtual navigation

描述（由申请人提供）：啮齿动物的空间导航是哺乳动物大脑认知、学习和记忆研究中广泛使用的范式。耻骨下是导航回路的重要输出结构，但很少有研究在行为动物中检查其生理学。本研究旨在确定单个枕下神经元在导航过程中如何从海马CA1区域的突触前输入中整合信息。CA1神经元形成对微小变化敏感的环境空间图；例如，从圆形腔室移动到方形腔室可以彻底改变CA1中的表示。另一方面，尽管从CA1接收了主要的输入，但下骨似乎形成了稳定的地图，在不同的环境中不会发生实质性的变化。下骨如何保持稳定的表征仍然是一个悬而未决的问题。为了在导航的背景下研究这些机制，Tank实验室最近开发了一种新的技术，用于钙成像和电生理记录，在虚拟环境中，在清醒的老鼠的大脑中进行导航。这项技术包括一个允许二维运动的球形跑步机，一个由球形跑步机上动物运动控制的虚拟现实环境，以及允许电生理记录或光学成像的可互换设备。与传统的导航研究方法相比，这种实验装置的一个主要优点是，动物的头部固定，但允许在虚拟环境中导航，为钙成像或全细胞记录提供稳定性。这也是一个优势，因为虚拟环境可以在导航任务中动态改变，提供对动物体验的完全控制。这个方案利用了这些新技术来理解下骨是如何形成环境地图的。在目的1中，钙活性的光学成像将用于描述什么样的环境变化改变了CA1的表现，但保留了骨下的地图。目的2将通过追踪单个枕骨下神经元的单突触输入来解决枕下电路的解剖组织。这些神经元包括来自CA1的输入和枕骨下的循环连接。在目标3中，这些技术将在单个动物中结合使用。将单个枕下神经元的空间表征与CA1和枕下单突触输入的表征进行比较。这一对比将阐明枕下神经元如何整合输入信号以形成稳定的表征。解开这个计算将有助于更普遍地理解海马体形成的作用。

DESCRIPTION (provided by applicant): Spatial navigation in rodents is a widely used paradigm for studies of cognition, learning, and memory in the mammalian brain. The subiculum is an important output structure for circuits that underlie navigation, yet few studies have examined its physiology in behaving animals. This proposal aims to identify how an individual subiculum neuron integrates information during navigation from its pre-synaptic inputs in the CA1 region of the hippocampus. CA1 neurons form a spatial map of the environment that is sensitive to small changes; for example, moving from a circular chamber to a square chamber can drastically alter the representation in CA1. The subiculum, on the other hand, seems to form stable maps that do not undergo substantial changes in different environments, despite receiving a major input from CA1. How the subiculum maintains a stable representation remains an open question. To investigate these mechanisms in the context of navigation, the Tank lab has recently developed new technology for calcium imaging and electrophysiological recordings to be performed in the brain of awake mice during navigation in a virtual environment. This technology consists of a spherical treadmill that allows for motion in two dimensions, a virtual reality environment controlled by the motion of the animal on the spherical treadmill, and interchangeable equipment allowing for either electrophysiological recordings or optical imaging. A major advantage of this experimental setup over conventional methods for studying navigation is that the animal is head-fixed, yet allowed to navigate within a virtual environment, providing stability for calcium imaging or whole cell recordings. It is also advantageous because the virtual environment can be dynamically altered during navigation tasks, providing complete control over the animal's experience. This proposal takes advantage of these new technologies in order to understand how the subiculum forms a map of the environment. In aim 1, optical imaging of calcium activity will be used to characterize what kinds of environmental alterations change the CA1 representation but preserve the map in the subiculum. Aim 2 will address the anatomical organization of subiculum circuitry by tracing mono-synaptic inputs to a single subiculum neuron. These neurons include inputs from CA1 and recurrent connections within the subiculum. In aim 3, these techniques will be combined in a single animal. The spatial representation in individual subiculum neurons will be compared to the representation of mono-synaptic inputs in CA1 and subiculum. This comparison will shed light on how subiculum neurons integrate incoming signals to form a stable representation. Unraveling this computation will help to understand the role of the hippocampal formation more generally.