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The anatomy of memory: an interactive overview of the parahippocampal–hippocampal network

Key Points

  • Comprehensive knowledge of the architecture of neuronal networks lies at the basis of understanding their functions. Although the anatomical connections between and within the hippocampal formation (HF) and the parahippocampal region (PHR) have been and still are being investigated extensively, for several reasons some of the PHR–HF network connections have become underexposed and this probably results in biased functional concepts.

  • We present a comprehensive interactive knowledge base of all anatomically established PHR–HF connections in the rat. Using this knowledge base, the PHR–HF circuitry is discussed and special attention is paid to underexposed connections.

  • The role of some of these underexposed connections is discussed in relation to three topics that are strongly associated with the PHR–HF network: memory formation, navigation and temporal dynamics.

  • Generally it is thought that only the HF is involved in memory formation, through associating different types of information. Based on the connections observed in the interactive diagram of the knowledge base, we pose that the entorhinal cortex associates information prehippocampally at a more generic level than the HF.

  • The CA3 recurrent network is the most prominent auto-associative network in the hippocampus and is implicated in pattern-separation and pattern-completion tasks that are relevant for memory. However, there are also recurrent networks in the hilus of the dentate gyrus, CA1 and the subiculum. They might also serve a unique role in memory, but they receive little attention.

  • Detailed anatomical knowledge lies at the basis of the discovery of grid cells that are important for navigation. Based on details of the entorhinal–hippocampal connections, we propose that there will be differences in the modulation of firing patterns along the transverse axis in CA1 and the subiculum. The proximal part of CA1 and the distal subiculum will preferentially process spatial information, whereas the distal part of CA1 and the proximal subiculum will process non-spatial information.

  • Although most track-tracing studies do not reveal whether a connection is excitatory or inhibitory, we suggest that some of the known connections between regions of the network are likely to be identified as inhibitory interneuron projections, based on their layer of origin. These long-range GABA (γ-aminobutyric acid)-ergic connections probably mediate interregional binding.

  • Sources of detailed knowledge, such as that presented in this Review and the accompanying interactive diagram, will prevent the loss of valuable knowledge and hopefully inspire creative minds to come up with new solutions for outstanding problems in the field.

Abstract

Converging evidence suggests that each parahippocampal and hippocampal subregion contributes uniquely to the encoding, consolidation and retrieval of declarative memories, but their precise roles remain elusive. Current functional thinking does not fully incorporate the intricately connected networks that link these subregions, owing to their organizational complexity; however, such detailed anatomical knowledge is of pivotal importance for comprehending the unique functional contribution of each subregion. We have therefore developed an interactive diagram with the aim to display all of the currently known anatomical connections of the rat parahippocampal–hippocampal network. In this Review, we integrate the existing anatomical knowledge into a concise description of this network and discuss the functional implications of some relatively underexposed connections.

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Figure 1: Representations of the hippocampal formation and the parahippocampal region in the rat brain.
Figure 2: Interactive diagram.
Figure 3: The standard view of parahippocampal–hippocampal circuitry.

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Acknowledgements

The authors would like to thank E. Moser and L. Colgin for providing helpful comments on an earlier version of this article. N.L.M.C. acknowledges a personal grant from the Netherlands Organization for scientific research (NWO) — grant number 903-47-074.

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Glossary

Temporal dynamics

Properties of neurons in a network, such as precise spike times and firing rates, that facilitate information transfer.

Convergence

When inputs from different brain regions congregate on to single cells or on to a local network in another region.

Reciprocal connections

Bidirectional, equivalent connections between two areas, networks or neurons.

Perforant pathway

Axons that originate in the superficial layers of the EC and are distributed to all fields of the hippocampus.

Divergence

When one brain region sends projections to several different brain regions.

Mossy fibres

The main projection of DG granular cells to CA3; characterized by high concentrations of zinc.

Schaffer collaterals

The axon collaterals of the CA3 pyramidal cells that project to CA1.

Auto-associative network

A network of neurons with axon collaterals that terminate on dendrites of the parent cell.

Place cells

Principal neurons in the hippocampus and parahippocampus that fire whenever an animal is in a specific location in an environment (corresponding to the cell's 'place field').

Grid cells

Neurons in the entorhinal cortex that fire strongly when an animal is at one of several specific locations in an environment and that are organized in a grid-like fashion.

Head-direction cells

Neurons that fire only when the animal's head points in a specific direction in an environment.

Mammillary bodies

A pair of nuclei in the hypothalamus, strongly connected to the HF and the anterior complex of the thalamus, that are involved in recognition memory.

Theta oscillations

Rhythmical changes at 5–12 Hz in network activity, as observed in the electroencephalogram, characteristic of the hippocampal network communicating with various cortical and subcortical networks in the brain.

Gamma oscillations

Rhythmical oscillations of 25–70 Hz observed in the electroencephalogram.

Ripple oscillations

Short-lasting bursts of field oscillations (140–200 Hz) in the mammalian hippocampus and parahippocampus that occur during rest or slow-wave sleep.

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van Strien, N., Cappaert, N. & Witter, M. The anatomy of memory: an interactive overview of the parahippocampal–hippocampal network. Nat Rev Neurosci 10, 272–282 (2009). https://doi.org/10.1038/nrn2614

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