A hippocampal mechanism for considering possibilities

描述（由申请人提供）：海马体在灵活的学习任务中起关键作用，特别是在空间导航、逆转、情景记忆任务和需要计划和决策的任务中。在具有空间成分的任务中，海马体细胞表现出强烈的空间放电相关（称为“位置场”）。由于可以从海马体中记录大型神经集合，并且由于位置场集通常覆盖整个环境，因此可以从海马体神经集合中重建位置。在空间决策任务中，非空间信息（情景记忆、要做的决定等）被投射到空间域。这意味着位置细胞的空间调节为研究决策任务中海马体表征的动态提供了杠杆作用。利用新的重构方法，我们可以在非常快（例如几十毫秒）的时间尺度上解释神经集合的空间位置表征，我们最近观察到一个可靠的、可重复的现象，每当大鼠在迷宫的决策点暂停时：在大多数行为中，由神经集合重建的位置准确地表示了大鼠在迷宫中的位置。然而，在决策点，重建的位置扫过老鼠的前方，首先沿着一条可能的路径，然后沿着另一条路径。在前后交替500- 1000毫秒后，表征返回到动物的位置，大鼠又开始跑步。这些非局部重建可靠地延伸到动物的前方，而不是动物的后方。我们的工作假设是，这种现象反映了一种选择考虑、路径或目标规划过程。这项提议的目的是验证这一假设，并进一步了解这些观察结果背后的机制。我们的研究计划是记录提示选择任务中的神经系统集合，并确定这些现象发生时的行为情况。当这些现象发生时，我们将确定老鼠的位置（例如，这是否只发生在选择时？）以及重建的位置（例如，它是否一路扫向目标？）然后，我们将通过与传入结构的详细比较，以及对海马局部场电位、中间神经元和锥体细胞放电模式及其相互作用的详细分析，来描述海马对这种现象的贡献。这里提出的工作将增加我们对海马体在空间导航、情景记忆和决策中的作用的理解。利用应用于神经集合记录的新分析技术，我们最近观察到，当大鼠在决策点暂停时，海马体集合会瞬间编码可用的选择。本提案的目的是了解这种新现象背后的机制，这可能反映了一个选择-考虑过程。了解正常决策过程的机制将对那些决策过程已经崩溃的患者产生影响，如焦虑症或其他认知障碍，如阿尔茨海默病和精神分裂症。

DESCRIPTION (provided by applicant): The hippocampus is critically involved in flexible learning tasks, particularly in spatial navigation, reversal, and episodic-memory tasks and tasks that require planning and decision-making. In tasks with a spatial component, hippocampal cells show a strong spatial firing correlate (termed "place fields"). Because it is possible to record large neural ensembles from hippocampus, and because the set of place fields generally cover the entire environment, it is possible to reconstruct location from hippocampal neural ensembles. In spatial decision tasks, non-spatial information (episodic memory, decisions to be made, etc.) is projected onto the spatial domain. This means that the spatial tuning of place cells provides leverage with which to examine the dynamics of hippocampal representations on decision tasks. Using new reconstruction methods that enable the interpretation of representation of spatial location from neural ensembles at very fast (e.g. tens of ms) timescales, we have recently observed a reliable, repeatable phenomenon whenever rats paused at a decision point on a maze: During most behaviors, location reconstructed from the ensemble was an accurate representation of the rat's location within the maze. However, at decision points, the reconstructed location swept ahead of the rat, first down one potential path, and then down the other. After alternating back and forth for 500- 1000 ms, the representation returned to the location of the animal and the rat began running again. These non-local reconstructions reliably stretched forward of the animal rather than behind the animal. Our working hypothesis is that this phenomenon reflects a choice-consideration, path-, or goal-planning process. The objective of this proposal is to test this hypothesis and further our understanding of the mechanisms underlying these observations. Our plan of attack is to record neural ensembles in a cued-choice task and to determine the behavioral situations in which these phenomena occur. We will identify the location of the rat when these phenomena occur (e.g. does this only occur at choices?) and the locations which get reconstructed to (e.g. does it sweep all the way to the goal?). We will then characterize the hippocampal contribution to the phenomena through detailed comparison with afferent structures and a detailed analysis of hippocampal local field potentials, interneuron and pyramidal cell firing patterns, and the interaction between them. The work proposed here will increase our understanding of the role of the hippocampus in spatial navigation, episodic memory, and decision-making. PUBLIC HEALTH RELEVANCE Using novel analysis techniques applied to neural ensemble recordings, we have recently observed that hippocampal ensembles transiently encode the available choices when rats pause at decision-points. This objective of this proposal is to understand the mechanisms underlying this novel phenomenon, which may reflect a choice-consideration process. Understanding the mechanisms of the normal decision-making process will have implications for patients in which that process has broken down such as in anxiety disorders or other cognitive disorders such as Alzheimer's disease and Schizophrenia.