Three-dimensional atlas framework for mapping of projections from the entorhinal cortex to the hippocampal formation in rat

Precise maps of the complex neural networks connecting different parts of the hippocampal formation and parahippocampus are needed to advance our understanding of mechanisms underlying memory and learning processes. The entorhinal cortex provides an interface between the hippocampal formation and the neocortex, and is considered to have a pivotal role in memory formation by gating signals to the hippocampus. Numerous investigations of the axonal connections between the entorhinal cortex and the hippocampal formation have provided an overwhelming amount of data describing laminar and topological patterns of organization. It is, however, challenging to appreciate both the subtle details as well as the overall organizational principles of these complex networks. To this end we have established a three-dimensional (3-D) atlas of the entorhinal projections to the hippocampal formation in rat. The atlas contains data from five experiments, in which an anterograde axonal tracer was injected at different locations in the entorhinal cortex. Images of histological sections showing the detailed trajectory of labelled axons are organized in a 3-D spatial framework, and image analysis tools are used to derive simplified representations of labelled axonal terminals. We demonstrate and compare regional and subregional topographical organization in the hippocampal formation. We conclude that this neuroinformatics based approach provides a powerful framework for gaining an overview of hippocampal neural networks, while simultaneously maintaining access to morphological details present in the original histological data.