Grid, border and head-direction circuits in the rodent Presubiculum.

神经元对外部环境（动物的位置）的明确属性做出反应的发现，为高端皮质中的神经编码提供了突破性的途径，复杂的认知和行为功能最有可能实现。位置细胞、网格细胞、头部方向细胞和边界细胞的发现，以及它们在行为过程中的动态相互作用，无疑是理解大脑内部计算的一个里程碑。然而，尽管在过去的几十年里取得了巨大的进步，我们仍然远离空间表征的机械理解。由于方法的限制，我们仍然知道很少的主要细胞多样性与空间编码;在高端皮质，空间表征（如网格，边界和头部方向）的细胞身份和电路仍然在很大程度上没有得到解决。在这里，我提出了一个新的研究议程来解决这个问题，并直接连接神经元的功能特性（在体内行为过程中评估）的细胞身份和电路。我们将重点放在前下托（PreS）-一个高端的皮质区域，这是一个主要的输入内侧内嗅皮层（MEC），其中大多数网格细胞已被发现。作为第一步，我们将系统地描述主要神经元在大鼠PreS结合在体外电生理逆行神经元示踪，分子分析和在体内标记的神经元的形态重建。为了解决不同细胞类型的空间放电相关性，我们将通过使用创新的神经细胞程序记录和标记自由行为动物中的单个PreS神经元。特别重点将致力于MEC投射神经元：通过长距离轴突填充，结合定量解剖分析，我们的目标是提供第一个功能布线图之间的PreS和MEC在亚细胞（singlge-bouton）分辨率。初步的数据表明，所提出的方法的可行性，并提供强有力的指示内PreS电路的结构-功能关系。总之，这种方法学上独特的单细胞方法（从功能到结构）将阐明解剖学上识别的细胞和电路如何有助于空间编码，从而为哺乳动物大脑中空间表征的细胞基础提供前所未有的见解。

The discovery of neurons which respond to a clear property of the external environment (the animal`s location) has provided groundbreaking access to neural coding in high-end cortices, where complex cognitive and behavioral functions are most likely to be implemented. The discovery of place cells, grid cells, head-direction cells and border cells, and their dynamic interactions during behavior, undoubtedly represents a milestone towards understanding internal brain computations. Yet, despite the immense progress over the past decades, we are still far from a mechanistic understanding of spatial representations. Due to methodological limitations, we still know very little about how principal cell diversity relates to spatial coding; in high end-cortices, the cell identity and circuits of spatial representations (e.g. grid, border and head-direction) have remained largely unresolved. Here I propose a novel research agenda to address this problem, and directly link neuronal functional properties (assessed in-vivo during behavior) to cell identity and circuits. We will focus on the Presubiculum (PreS) - a high-end cortical region which contributes a major input to Medial Entorhinal Cortex (MEC), where most grid cells have been found. As a first step, we will systematically characterize principal neurons in the rat PreS by combining in-vitro electrophysiology with retrograde neuronal tracing, molecular analysis and morphological reconstructions of in-vivo labeled neurons. To resolve the spatial firing correlates of the different cell types, we will record and label individual PreS neurons in freely behaving animals by using innovative juxtacellular procedures. Particular focus will be devoted to MEC-projecting neurons: by means of long-range axonal filling, in combination with quantitative anatomical analysis, we aim at providing the first functional wiring diagram between PreS and MEC at subcellular (sinlge-bouton) resolution. Preliminary data demonstrate the feasibility of the proposed approach, and provide strong indications for structure-function relationships within PreS circuits. In summary, this methodologically-unique single-cell approach (from function to structure) will elucidate how anatomically-identified cells and circuits contribute to spatial coding, and thus provide unprecedented insights into the cellular basis of space representations in the mammalian brain.