From Rapid Place Learning to Behavioral Performance: A Key Role for the Intermediate Hippocampus

Tobias Bast,Iain A Wilson,Richard G M Morris,Menno P Witter,Mick D Rugg

doi:10.1371/journal.pbio.1000089

Abstract

Rapid place encoding by hippocampal neurons, as reflected by place-related firing, has been intensely studied, whereas the substrates that translate hippocampal place codes into behavior have received little attention. A key point relevant to this translation is that hippocampal organization is characterized by functional–anatomical gradients along the septotemporal axis: Whereas the ability of hippocampal neurons to encode accurate place information declines from the septal to temporal end, hippocampal connectivity to prefrontal and subcortical sites that might relate such place information to behavioral-control processes shows an opposite gradient. We examined in rats the impact of selective lesions to relevant parts of the hippocampus on behavioral tests requiring place learning (watermaze procedures) and on in vivo electrophysiological models of hippocampal encoding (long-term potentiation [LTP], place cells). We found that the intermediate hippocampus is necessary and largely sufficient for behavioral performance based on rapid place learning. In contrast, a residual septal pole of the hippocampus, although displaying intact electrophysiological indices of rapid information encoding (LTP, precise place-related firing, and rapid remapping), failed to sustain watermaze performance based on rapid place learning. These data highlight the important distinction between hippocampal encoding and the behavioral performance based on such encoding, and suggest that the intermediate hippocampus, where substrates of rapid accurate place encoding converge with links to behavioral control, is critical to translate rapid (one-trial) place learning into navigational performance.

Highlights

A classical distinction in animal learning theory is that between ‘‘learning’’ and ‘‘performance’’ [1,2]
We examined the impact of selective lesions to distinct parts of the hippocampus on behavior requiring rapid place learning and on in vivo electrophysiological models of hippocampal learning such as place-related neuronal activity
We showed that translation of rapid place learning into efficient search behavior requires the ‘‘intermediate’’ region of the hippocampus, a region that likely combines anatomical links to visuospatial information processed by the neocortex with links to behavioral control through prefrontal cortex and subcortical sites

Summary

Introduction

A classical distinction in animal learning theory is that between ‘‘learning’’ and ‘‘performance’’ [1,2]. Recent research has focused on how neocortical visuospatial inputs, entering the hippocampus from the entorhinal cortex [15,16,17,18], are processed by different subregions along the transverse and longitudinal axes of the hippocampus to mediate place representations. This work has revealed that different subregions along the hippocampal transverse axis (dentate gyrus, CA3, and CA1) make distinct computational contributions, including rapid encoding and pattern completion (CA3) [19,20,21,22], pattern separation (dentate gyrus and CA3) [23,24], and the comparison of new and stored information (CA1) [25,26,27]. With respect to the precision of visuospatial encoding, it is critical that the septal to intermediate hippocampus exhibit strong connectivity to the dorsolateral domain of the entorhinal cortex, which receives strong visuospatial neocortical inputs and where neurons, so-called grid cells, represent visuospatial informa-

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Discussion

Conclusion