NEURAL BASIS OF INTERNAL REPRESENTATION OF PLACE

描述(改编自申请人的摘要)：本提案意在 进一步加深对海马区信息内部动力学的理解 可帮助有效存储和检索序列的处理 信息。在其他方面，海马体结构对于 具有时间维度的某些类型的存储器，例如用于 情节、参观地点的顺序、通往目标的路线以及关联 弥合时间鸿沟的条件反射。几种理论表明， 海马体的解剖和生理组织可能是 特别适合于序列数据的编码和存储 事件之间的关系，我们已经获得了存储和 海马神经元整体活动序列的检索。一个序列 A-B-C可以通过选择性地加强从A到B的突触来学习，因此 第四，然而，有两个主要制约因素。其一是神经 要按顺序关联的模式必须相对于 联合机制的时间常数(例如，NMDA受体)。否则 网络被困在一个州。例如，序列A-A-B-B0-C-C 可能会卡住，但A-B0C不会。另一个限制是，如果 重复输入序列，然后是顺序(时间)上下文信息 必须进行编码，否则对下一项的预测将变得不明确。因此，在 序列A-B-C-B-D，如果C和D要进行编码，则两个B必须不同地编码 被正确地取回。海马神经系综的动力学研究 表示法显示了两个可用于克服这些问题的属性 约束条件。首先，当一只动物通过一个给定的 锥体(‘Place’)细胞，该细胞在theta节律周期中较晚开始放电 随着大鼠穿过 场(一种称为“位相进动”的现象)。这意味着一次滑动 位场的全局序列的窗口以压缩的方式复制 在每个周期内形成，从而使系综码在开始和结束处 基本不相关的塞塔循环。这可以解决第一个问题 约束，即代码的快速更改。对起源的更好理解 位相进动效应与信息流动力学的关系 然而，为了验证这一假设，必须达到这一点。第二， 海马体的特性是能够产生完全不同的代码 对于相同的空间位置，取决于行为和其他上下文 变量。因此，它还能够正交化位置表示，该位置表示 作为序列的歧义元素出现，从而解决了歧义 顺序问题；但这一点需要确定。此外，要了解 海马体在空间和一般情节记忆中的作用，它是 有必要更好地理解支配 海马神经元活动的空间和时间尺度。这些实验 本提案中描述的解决这些问题。

DESCRIPTION (Adapted from Applicant's abstract): This proposal is intended to further our understanding of the internal dynamics of hippocampal information processing that may assist in the efficient storage and retrieval of sequence information. Among other things, the hippocampal formation is necessary for certain kinds of memory that have a temporal dimension, such as memory for episodes, serial order of places visited, routes to goals, and associative conditioning that bridges temporal gaps. Several theories suggest that the anatomical and physiological organization of the hippocampus may be particularly well suited to the encoding and storage of sequential relationships among events, and we have obtained evidence for the storage and retrieval of sequences of hippocampal neuronal ensemble activity. A sequence A-B-C can be learned by selectively strengthening synapses from A to B, and so forth; however there are two principal constraints. One is that the neural patterns to be sequentially associated must change rapidly relative to the time-constant of the associative mechanism (e.g., the NMDA receptor). Otherwise the network gets trapped in one state. For example, the sequence A-A-B-B0-C-C might get stuck but A-B0C would not. The other constraint is that, if items of the input sequence are repeated, then sequential (temporal) context information must be encoded or the prediction of the next item becomes ambiguous. Thus, in a sequence A-B-C-B-D, the two Bs must be encoded differently if C and D are to be retrieved correctly. The dynamics of hippocampal neural ensemble representations exhibit two properties that may serve to overcome these constraints. First, when an animal passes through the "place field" of a given pyramidal ('place') cell, the cell begins firing late in the theta rhythm cycle and the firing phase shifts progressively earlier as the rat runs through the field (a phenomenon known as "phase precession"). This means that a sliding window of the global sequence of place fields is replicated in a compressed form within each cycle, thus making the ensemble codes at the beginning and end of the theta cycle essentially uncorrelated. This could solve the first constraint i.e., rapid change of the code. A better understanding of the origin of the phase precession effect and the dynamics of information flow in relation to it must be reached, however, in order to verify this hypothesis. Second, the hippocampus has the property of being able to create completely different codes for the same spatial location, depending on behavioral and other contextual variables. It may thus also be able to orthogonalize place representations that occur as ambiguous elements of sequences, thereby solving the ambiguous sequence problem; but this needs to be determined. In addition, to understand the role of the hippocampus in both spatial and general episodic memory, it is necessary to achieve a better understanding of the factors that govern the spatial and temporal scales of hippocampal neuronal activity. The experiments described in this proposal address these issues.