pubmed.ncbi.nlm.nih.gov

Hilar mossy cell circuitry controlling dentate granule cell excitability - PubMed

  • ️Tue Jan 01 2013

Review

Hilar mossy cell circuitry controlling dentate granule cell excitability

Seiichiro Jinde et al. Front Neural Circuits. 2013.

Abstract

Glutamatergic hilar mossy cells of the dentate gyrus can either excite or inhibit distant granule cells, depending on whether their direct excitatory projections to granule cells or their projections to local inhibitory interneurons dominate. However, it remains controversial whether the net effect of mossy cell loss is granule cell excitation or inhibition. Clarifying this controversy has particular relevance to temporal lobe epilepsy, which is marked by dentate granule cell hyperexcitability and extensive loss of dentate hilar mossy cells. Two diametrically opposed hypotheses have been advanced to explain this granule cell hyperexcitability-the "dormant basket cell" and the "irritable mossy cell" hypotheses. The "dormant basket cell" hypothesis proposes that mossy cells normally exert a net inhibitory effect on granule cells and therefore their loss causes dentate granule cell hyperexcitability. The "irritable mossy cell" hypothesis takes the opposite view that mossy cells normally excite granule cells and that the surviving mossy cells in epilepsy increase their activity, causing granule cell excitation. The inability to eliminate mossy cells selectively has made it difficult to test these two opposing hypotheses. To this end, we developed a transgenic toxin-mediated, mossy cell-ablation mouse line. Using these mutants, we demonstrated that the extensive elimination of hilar mossy cells causes granule cell hyperexcitability, although the mossy cell loss observed appeared insufficient to cause clinical epilepsy. In this review, we focus on this topic and also suggest that different interneuron populations may mediate mossy cell-induced translamellar lateral inhibition and intralamellar recurrent inhibition. These unique local circuits in the dentate hilar region may be centrally involved in the functional organization of the dentate gyrus.

Keywords: epileptogenesis; excitability; granule cells; hippocampal mossy fibers; lateral inhibition; mossy cells; pattern separation; temporal lobe epilepsy.

PubMed Disclaimer

Figures

Figure 1
Figure 1

Schematic of the connectivity of hilar mossy cells and toxin-induced mossy cell degeneration. (A) Mossy fiber axon collaterals of dentate granule cells are the main input to the mossy cells at their proximal dendrites, called “thorny excrescences.” Mossy cells also receive strong excitatory inputs from semilunar granule cells at the relatively distal dendritic segments of mossy cells. A fraction of CA3 pyramidal cells “backproject” to mossy cells which also receive scarce input directly from the entorhinal cortex. Mossy cells also receive GABAergic inputs from hilar interneurons. Other inputs such as cholinergic and noradrenergic projections are known to modulate mossy cell activity. Mossy cell axons project to the dentate inner molecular layer (IML) along the septo-temporal axis and further contra-lateral hippocampus, where over 90% of asymmetric synaptic contacts are formed on granule cell proximal dendrites as well as semilunar granule cells. Mossy cells also send axon collaterals to dentate GABAergic interneurons in the different lamellae or in the contra-lateral hippocampus. Mutual connections between mossy cells are rare. For simplicity, not all the connections are shown. Ach, acetylcholine; EC, entorhinal cortex; GC, granule cell; GCL, granule cell layer; IN, interneuron; MC, mossy cell; NA, noradrenaline; PC, pyramidal cell; SGC, semilunar granule cell; 5-HT, serotonin. (B) Representative photographs of Nissl staining showing histological alterations in the hilar region in CA3c/mossy cell-cre/floxed-diphtheria toxin receptor mutant mouse (right) 4 weeks after diphtheria toxin (DT) administration. Compared to DT-treated control (left), mutant mouse showed the decreased cell number in the dentate hilus. Scale bar, 100 μm.

Figure 2
Figure 2

Two hypothetical modes for mossy cell-driven feed-forward inhibition of granule cells. Based on our findings, dentate granule cells appear to be inhibited by two distinct categories of interneurons in light of fast- or slow-rise kinetics of postsynaptic GABAA receptors. We propose that granule cells located in the same lamellae receive inhibition from interneurons (In A; interneuron A) which display slow-rise time kinetics of sIPSCs at the granule cell dendrites. Conversely, granule cells translamellar to the mossy cells may receive perisomatic inhibition from interneurons (In B; interneuron B) that display fast-rise time kinetics. While the nature of those interneurons is uncertain, we suspect interneurons translamellar to the mossy cells are basket cell-like cells. For simplicity, the dendrites of mossy cells and interneurons are omitted. GC, granule cell; GCL, granule cell layer; MC, mossy cell; ML, molecular layer; PL, polymorphic layer.

Similar articles

Cited by

References

    1. Aimone J. B., Deng W., Gage F. H. (2011). Resolving new memories: a critical look at the dentate gyrus, adult neurogenesis, and pattern separation. Neuron 70, 589–596 10.1016/j.neuron.2011.05.010 - DOI - PMC - PubMed
    1. Ali A. B., Thomson A. M. (2008). Synaptic α5 subunit–containing GABAA receptors mediate IPSPs elicited by dendrite-preferring cells in rat neocortex. Cereb. Cortex 18, 1260–1271 10.1093/cercor/bhm160 - DOI - PubMed
    1. Amaral D. G. (1978). A Golgi study of cell types in the hilar region of the hippocampus in the rat. J. Comp. Neurol. 182, 851–914 - PubMed
    1. Amaral D. G., Scharfman H. E., Lavenex P. (2007). The dentate gyrus: fundamental neuroanatomical organization (dentate gyrus for dummies). Prog. Brain Res. 163, 3–22 10.1016/S0079-6123(07)63001-5 - DOI - PMC - PubMed
    1. Amaral D. G., Witter M. P. (1989). The three-dimensional organization of the hippocampal formation: a review of anatomical data. Neuroscience 31, 571–591 10.1016/0306-4522(89)90424-7 - DOI - PubMed

Publication types

MeSH terms

LinkOut - more resources