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Hilar mossy cell circuitry controlling dentate granule cell excitability.

Jinde S, Zsiros V, Nakazawa K - Front Neural Circuits (2013)

Bottom Line: However, it remains controversial whether the net effect of mossy cell loss is granule cell excitation or inhibition.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.These unique local circuits in the dentate hilar region may be centrally involved in the functional organization of the dentate gyrus.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo Tokyo, Japan.

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.

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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.
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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.

Mentions: Furthermore, analysis of granule cell-rise time separated in these preparation raises a possibility that two distinct types of interneurons that provide IPSCs of, project to the same granule cells, in relation to the location of mossy cells activating them (Figure 2). One group of interneurons target granule cells with IPSCs of slow-rise time kinetics, and they are located close to the mossy cells, e.g., they receive excitation from those mossy cells in an intra-lamellar manner. Another group is the interneurons with fast-rise time kinetics, which are located translamellar to the mossy cells, again receiving excitatory projection from those mossy cells. Since slow-rise time kinetics interneurons compose of only 30% of inhibition, we think mossy cell feed-forward inhibition is largely translamellar, which was first demonstrated by Zappone and Sloviter (2004).


Hilar mossy cell circuitry controlling dentate granule cell excitability.

Jinde S, Zsiros V, Nakazawa K - Front Neural Circuits (2013)

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.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3569840&req=5

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.
Mentions: Furthermore, analysis of granule cell-rise time separated in these preparation raises a possibility that two distinct types of interneurons that provide IPSCs of, project to the same granule cells, in relation to the location of mossy cells activating them (Figure 2). One group of interneurons target granule cells with IPSCs of slow-rise time kinetics, and they are located close to the mossy cells, e.g., they receive excitation from those mossy cells in an intra-lamellar manner. Another group is the interneurons with fast-rise time kinetics, which are located translamellar to the mossy cells, again receiving excitatory projection from those mossy cells. Since slow-rise time kinetics interneurons compose of only 30% of inhibition, we think mossy cell feed-forward inhibition is largely translamellar, which was first demonstrated by Zappone and Sloviter (2004).

Bottom Line: However, it remains controversial whether the net effect of mossy cell loss is granule cell excitation or inhibition.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.These unique local circuits in the dentate hilar region may be centrally involved in the functional organization of the dentate gyrus.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo Tokyo, Japan.

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.

Show MeSH
Related in: MedlinePlus