Trends in Neurosciences
OpinionMossy cells in epilepsy: rigor mortis or vigor mortis?
Section snippets
Mossy cells: a case of neurons living dangerously?
A caricature of mossy cells is that they are so vulnerable they behave like fuses, and that their rapid death breaks the circuit after a dangerous surge in electrical activity in the network [21]. What are the mossy cell properties that could enable these cells to blow so easily and serve as self-sacrificing neuronal fuses? First and foremost, mossy cells give and receive excitatory synapses to and from granule cells, an arrangement that provides a positive feedback circuit 23, 24, 25, 26.
Mossy cells lost and found
Owing to the lack of mossy cell-specific neuronal markers, most of the data upon which the ideas of selective vulnerability and widespread loss of mossy cells rested are based on indirect evidence, such as equating hilar cell loss from Nissl stains with mossy cell loss or studying changes in the number of cells that lack expression for glutamate decarboxylase (GAD65/67), the synthesizing enzyme for the inhibitory neurotransmitter GABA. However, inferences based on such indirect approaches are
Can both loss and survival of mossy cells be pro-convulsive?
As far as the long-term decrease in threshold for seizures is concerned, is it the lost or the surviving mossy cells that are truly important? While the answer to this question remains to be determined, it is instructive to compare the predictions of three theories.
The first of these is essentially the ‘mossy cell loss causes mossy fiber sprouting’ hypothesis (Fig. 3a). As mossy fibers (the axons of granule cells) heavily innervate mossy cells, it has generally been believed that the loss of
Is the hilus half full or half empty in epilepsy?
Seizures beget seizures [58]; mossy fiber activity triggers mossy cell loss that triggers mossy fiber sprouting [45]; interneurons hyper-synchronize principal cells [59]; interneuronal heterogeneity regulates excitability [60]; increased inhibition 61, 62, 63, 64, 65, 66, 67, 68, 69 becomes converted to hyperexcitability [70]: these are just some of the challenging ideas that have arisen from recent results in epilepsy research. These possibilities vividly illustrate the web-like complexity and
Acknowledgements
This work was supported by the NIH (grant NS35915 to I.S.).
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