Mossy cells in epilepsy: rigor mortis or vigor mortis?

Ratzliff, Anna; Santhakumar, Vijayalakshmi; Howard, Allyson; Soltész, Iván

doi:10.1016/s0166-2236(00)02122-6

Cited by 146 publications

(143 citation statements)

References 68 publications

Supporting

Mentioning

129

Contrasting

Unclassified

Order By: Relevance

“…These data do not confirm the predictions of the dormant basket cell hypothesis (Sloviter, 1991(Sloviter, , 1994. However, these results are in agreement with alternative mechanistic roles for mossy cells during epileptogenesis (Ratzliff et al, 2002).…”

Section: Mossy Cell Loss and Epileptogenesiscontrasting

confidence: 82%

“…The methods used to obtain these data had several advantages. First, prelabeled mossy cells could be identified in living slices without the laborintensive post hoc identification that is normally required to differentiate mossy cells from hilar interneurons (Santhakumar et al, 2000;Ratzliff et al, 2002). Second, the rapid ablation of mossy cells was critical, because the several-day time period needed for the in vivo genetic-or toxin-mediated cell-specific ablation techniques (Shah and Jay, 1993) could have allowed for concurrent confounding changes in protein expression or connectivity, such as mossy fiber sprouting, to occur (Sutula et al, 1988;BrooksKayal et al, 1998).…”

Section: Rapid and Spatially Selective Nature Of The Ablation Techniquementioning

confidence: 99%

“…The loss of neurons from the hilus is frequently associated with dentate hyperexcitability (Lowenstein et al, 1992;Toth et al, 1997;Santhakumar et al, 2001), but the precise nature of the relationship between the loss of hilar cells and the development of hyperexcitability in the dentate gyrus is not well understood (Ratzliff et al, 2002). A central question is whether it is the insult-induced functional removal of hilar cells from the neuronal circuit or the reactive changes subsequent to the hilar cell loss (e.g., mossy fiber sprouting, gliosis, and altered gene expression patterns) that lead directly to epileptogenesis.…”

Section: Introductionmentioning

confidence: 99%

“…A central question is whether it is the insult-induced functional removal of hilar cells from the neuronal circuit or the reactive changes subsequent to the hilar cell loss (e.g., mossy fiber sprouting, gliosis, and altered gene expression patterns) that lead directly to epileptogenesis. Although insults often lead to reductions in the number of both the glutamatergic mossy cells and the GABAergic hilar interneurons, it is the loss of mossy cells that has been thought to be the key event that results in dentate hyperexcitability, presumably because of the reportedly extreme vulnerability and long associative and commissural connections of mossy cells (for review, see Ratzliff et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

Ratzliff¹,

Howard²,

Santhakumar³

et al. 2004

J. Neurosci.

108

View full text Add to dashboard Cite

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.

show abstract

Section: Mossy Cell Loss and Epileptogenesiscontrasting

confidence: 82%

Section: Rapid and Spatially Selective Nature Of The Ablation Techniquementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Ratzliff¹,

Howard²,

Santhakumar³

et al. 2004

J. Neurosci.

108

View full text Add to dashboard Cite

show abstract

“…However, very little is known about eCB signaling in this area and what potential role it may play. eCBs may have a significant functional impact on this system since, intriguingly, mossy cells excite, and are excited by, dentate granule cells (Buckmaster et al, 1992;Ratzliff et al, 2002;Scharfman, 1995). This positive feedback loop may predispose these cells to excitotoxic cell death.…”

Section: Introductionmentioning

confidence: 99%

Input-specific plasticity at excitatory synapses mediated by endocannabinoids in the dentate gyrus

Chiu

Castillo

2008

Neuropharmacology

View full text Add to dashboard Cite

SummaryEndocannabinoids (eCBs) mediate transient and long-lasting synaptic plasticity in several brain structures. In the dentate gyrus, activation of the type 1 cannabinoid receptor (CB1R) by exogenous ligands reportedly depresses excitatory synaptic transmission. However, direct evidence of eCB signaling at excitatory synapses in this region has been lacking. Here, we demonstrate that eCB release can be induced by a brief postsynaptic depolarization of dentate granule cells (DGCs), which potently and transiently suppresses glutamatergic inputs from mossy cell interneurons (MCs) but not from entorhinal cortex via the lateral and medial perforant paths. This input-specific depolarizationinduced suppression of excitation (DSE) is calcium-dependent and can be modulated by agonists of cholinergic and group I metabotropic glutamate receptors. Inhibiting the synthesis of 2-arachidonoyl glycerol (2-AG), one of the most abundant eCBs in the brain, by diacyglycerol lipase (DGL) does not abolish DSE. Moreover, preventing the breakdown of anandamide, the other main eCB, does not potentiate DSE. Thus, eCB signaling underlying DSE in the dentate does not require DGL activity and is unlikely to be mediated by anandamide. Finally, we find that manipulations known to induce eCB-LTD at other central synapses do not trigger LTD at MCF-DGC synapses.

show abstract

“Dormant basket cell” hypothesis revisited: Relative vulnerabilities of dentate gyrus mossy cells and inhibitory interneurons after hippocampal status epilepticus in the rat

Sloviter

Zappone

Harvey

et al. 2003

J of Comparative Neurology

216

175

View full text Add to dashboard Cite

The "dormant basket cell" hypothesis suggests that postinjury hippocampal network hyperexcitability results from the loss of vulnerable neurons that normally excite insult-resistant inhibitory basket cells. We have reexamined the experimental basis of this hypothesis in light of reports that excitatory hilar mossy cells are not consistently vulnerable and inhibitory basket cells are not consistently seizure resistant. Prolonged afferent stimulation that reliably evoked granule cell discharges always produced extensive hilar neuron degeneration and immediate granule cell disinhibition. Conversely, kainic acid-induced status epilepticus in chronically implanted animals produced similarly extensive hilar cell loss and immediate granule cell disinhibition, but only when granule cells discharged continuously during status epilepticus. In both preparations, electron microscopy revealed degeneration of presynaptic terminals forming asymmetrical synapses in the mossy cell target zone, including some terminating on gamma-aminobutyric acid-immunoreactive elements, but no evidence of axosomatic or axoaxonic degeneration in the adjacent granule cell layer. Although parvalbumin immunocytochemistry and in situ hybridization revealed decreased staining, this apparently was due to altered parvalbumin expression rather than basket cell death, because substance P receptor-positive interneurons, some of which contained residual parvalbumin immunoreactivity, survived. These results confirm the inherent vulnerability of dendritically projecting hilar mossy cells and interneurons and the relative resistance of dentate inhibitory basket and chandelier cells that target granule cell somata. The variability of hippocampal cell loss after status epilepticus suggests that altered hippocampal structure and function cannot be assumed to cause the spontaneous seizures that develop in these animals and highlights the importance of confirming hippocampal pathology and pathophysiology in vivo in each case.

show abstract

Mossy cells in epilepsy: rigor mortis or vigor mortis?

Cited by 146 publications

References 68 publications

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

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

Input-specific plasticity at excitatory synapses mediated by endocannabinoids in the dentate gyrus

“Dormant basket cell” hypothesis revisited: Relative vulnerabilities of dentate gyrus mossy cells and inhibitory interneurons after hippocampal status epilepticus in the rat

Contact Info

Product

Resources

About