A hippocampal mechanism for considering possibilities

描述(申请人提供)：海马体主要参与灵活的学习任务，特别是在空间导航、反转和情景记忆任务以及需要计划和决策的任务中。在具有空间成分的任务中，海马细胞表现出很强的空间放电关联(称为“位置场”)。因为可以从海马区记录大的神经群，并且因为位置场集合通常覆盖整个环境，所以从海马区神经群重建位置是可能的。在空间决策任务中，非空间信息(情节记忆、要做出的决定等)投射到空间域上。这意味着，位置细胞的空间调谐提供了杠杆，用来检查决策任务中海马体表征的动态。 使用新的重建方法，能够在非常快的(例如，几十毫秒)的时间尺度上解释来自神经集合的空间位置表示，我们最近观察到了一个可靠的、可重复的现象：在大多数行为中，从集合重建的位置是老鼠在迷宫中的位置的准确表示。然而，在决策点，重建的位置扫在老鼠的前面，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，表征返回到动物所在的位置，老鼠再次开始奔跑。这些非局部重建可靠地延伸到动物的前方，而不是动物的后面。我们的工作假设是，这种现象反映了一个选择-考虑、路径-或目标-规划过程。这项提议的目的是检验这一假设，并进一步了解这些观察的基础机制。 我们的攻击计划是在提示选择任务中记录神经集合，并确定这些现象发生的行为情景。当这些现象发生时，我们将确定老鼠的位置(例如，这种情况是否只发生在选择？)以及重建到的位置(例如，它是否一直扫描到目标？)。然后，我们将通过与传入结构的详细比较和对海马局部场电位、中间神经元和锥体细胞的放电模式以及它们之间的相互作用的详细分析，来表征海马对这一现象的贡献。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。使用新的分析技术应用于神经系综录像，我们有 最近观察到，海马区的集合瞬间编码了可用的选择 当老鼠在决策点停下来的时候。这项建议的目的是理解 这种新现象背后的机制，这可能反映了一种选择- 考虑过程。理解正常决策的机制 这一过程将对患者产生影响，在这些患者中，该过程已经破坏了 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. 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.