The dentate gyrus as a filter or gate: a look back and a look ahead

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Abstract

The idea of the dentate gyrus as a gate or filter at the entrance to the hippocampus, blocking or filtering incoming excitation from the entorhinal cortex, has been an intriguing one. Here we review the historical development of the idea, and discuss whether it may be possible to be more specific in defining this gate. We propose that dentate function can be understood within a context of Hebbian association and competition: hilar mossy cells help the dentate granule cells to recognize incoming entorhinal patterns of activity (Hebbian association), after which patterns that are consistently and repetitively presented to the dentate gyrus are passed through, while random, more transient patterns are blocked (non-associative Hebbian competition). Translamellar inhibition as well as translamellar potentiation can be understood in this context. The dentate-hilar complex thus plays the role of a “pattern excluder”, not a pattern completer. The unique role of pattern exclusion may explain the peculiar qualities of dentate granule cells and hilar mossy cells.

Introduction

The dentate gyrus, sitting between the entorhinal cortex and area CA3, is both anatomically well positioned and physiologically predisposed to play the role of a gate, blocking or filtering excitatory activity from the entorhinal cortex and controlling the amount of excitation that gets through to the hippocampus. Normal adult granule cells rarely generate action potentials. In part this is because there is little direct interconnectivity between dentate granule cells under normal conditions (reviewed in Chapter 1 of this volume). In addition, granule cells have a high resting membrane potential (Fricke and Prince, 1984; Scharfman, 1992; Staley et al., 1992; Williamson et al., 1993), and strong GABA receptor-mediated inhibition (Mody et al., 1992; Coulter, 1999; Nusser and Mody, 2002; Stell and Mody, 2002; Cohen et al., 2003; Mody, 2005).

Section snippets

History of the idea

Data that the dentate gyrus may serve as a gate appeared in at least as early as 1966 in work by Andersen et al. (1966). In these experiments, the hippocampal formation of adult rabbits was exposed by removal of the overlying neocortex and corpus callosum. Stimulating electrodes were placed into entorhinal cortex or in the perforant pathway. Extracellular as well as intracellular recordings were made from electrodes placed in the transverse plane of the hippocampus, piercing CA1 and both blades

The idea of dentate gate vs. filter

In summary, there is now a series of studies, which suggest that activity in the entorhinal cortex is often halted, delayed, or diminished at the dentate gyrus. The decreased excitability appears to be related at least in part to the strong, prolonged dentate granule cell IPSP first described by Andersen et al. (1966). Further, as also found in that study, repetitive perforant pathway stimulation for a prolonged period of time (a few seconds or longer) results in facilitation of succeeding

Dentate-hilar filtering function: a hypothesis

Various ways in which mossy cells can help the dentate gyrus function as a filter have been proposed. Buckmaster and Schwartzkroin (1994) have suggested a granule cell association hypothesis, wherein the mossy cells help to link subpopulations of granule cells. They suggested that the dentate-hilar role is one of pattern recognition, where the role of the mossy cells is to fill in missing components of perforant pathway input. For example, if the dentate-hilar complex learns to recognize a

A look ahead

Our conjecture for dentate-hilar function is speculative, but testable. The simplest type of experiment would be to monitor all EPSPs from the dentate granular layer in one lamella, and to calculate the initial slope of each EPSP, denoted E in units of volts per second. One would also keep track of which E's result in population spikes. Then a distribution function can be constructed, G(E), giving the probability of observing each value of E (Fig. 2, filled squares). One can also determine the

Acknowledgments

I am grateful to Drs. Helen Scharfman and Thomas Sutula for helpful advice and for the opportunity to write this chapter. I also thank the American Epilepsy Society for support, and the National Institutes of Health and National Center for Research Resources K12 Roadmap, Project number 8K12RR023268-02.

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