Rapid Deletion of Mossy Cells Does Not Result in a Hyperexcitable Dentate Gyrus: Implications for Epileptogenesis

By A. Ratzliff, Allyson L. Howard, V. Santhakumar, Imola Osapay, Ivan Soltesz. 2004

109 citations recorded by the source corpus.

Loss of cells from the hilus of the dentate gyrus is a major histological hallmark of human temporal lobe epilepsy. Hilar mossy cells, in particular, are thought to show dramatic numerical reductions in pathological conditions, and one prominent theory of epileptogenesis is based on the assumption that mossy cell loss directly results in granule cell hyperexcitability. However, whether it is the disappearance of hilar mossy cells from the dentate gyrus circuitry after various insults or the subsequent synaptic-cellular alterations (e.g., reactive axonal sprouting) that lead to dentate hyperexcitability has not been rigorously tested, because of the lack of available techniques to rapidly remove specific classes of nonprincipal cells from neuronal networks. We developed a fast, cell-specific ablation technique that allowed the targeted lesioning of either mossy cells or GABAergic interneurons in horizontal as well as axial (longitudinal) slices of the hippocampus. The results demonstrate that mossy cell deletion consistently decreased the excitability of granule cells to perforant path stimulation both within and outside of the lamella where the mossy cell ablation took place. In contrast, ablation of interneurons caused the expected increase in excitability, and control aspirations of the hilar neuropil or of interneurons in the presence of GABA receptor blockers caused no alteration in granule cell excitability. These data do not support the hypothesis that loss of mossy cells from the dentate hilus after seizures or traumatic brain injury directly results in hyperexcitability.

Subfields: Cellular and Molecular Neuroscience, Cognitive Neuroscience, Developmental Neuroscience

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cellular and Molecular Neuroscience

In Cognitive Neuroscience

In Developmental Neuroscience

Citations in the corpus

Re-evaluating circuit mechanisms underlying pattern separation (2019, neutral): “Mossy cell deletion studies have also found mixed effects on granule cell activity (Ratzliff et al., 2004; Jinde et al., 2012).”
Hilar Mossy Cell Degeneration Causes Transient Dentate Granule Cell Hyperexcitability and Impaired Pattern Separation (2012, unknown): “, 1983; Bilkey and Goddard, 1987), it has recently been suggested that under normal conditions, their net effect is excitatory (Ratzliff et al., 2004; Myers and Scharfman, 2009).”
In vivo imaging of dentate gyrus mossy cells in behaving mice (2017, background): “This strategy labeled hilar but not CA3 neurons (Figure 1B), and in agreement with previous reports (Ratzliff et al., 2004), the vast majority of retrogradely labeled hilar neurons”
Dendrites of dentate gyrus granule cells contribute to pattern separation by controlling sparsity (2016, result): “These findings are in line with the experimental data of (Ratzliff et al., 2004) where MC-loss did not lead to an over-excitation of GCs.”
Pattern Separation in the Dentate Gyrus: A Role for the CA3 Backprojection (2010, background): “cells or interneurons on granule cells activation (Ratzliff et al., 2004).”
A Role for Hilar Cells in Pattern Separation in the Dentate Gyrus: A Computational Approach (2009, methodology): “For example, Ratzliff et al. (2004) performed a specific ablation of a subset of hilar mossy cells or interneurons in hippocampal slices.”