Hilar mossy cell circuitry controlling dentate granule cell excitability
Open Access
- 1 January 2013
- journal article
- review article
- Published by Frontiers Media SA in Frontiers in Neural Circuits
- Vol. 7, 14
- https://doi.org/10.3389/fncir.2013.00014
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
This publication has 86 references indexed in Scilit:
- Mnemonic representations of transient stimuli and temporal sequences in the rodent hippocampus in vitroNature Neuroscience, 2012
- Pattern Separation: A Common Function for New Neurons in Hippocampus and Olfactory BulbNeuron, 2011
- Resolving New Memories: A Critical Look at the Dentate Gyrus, Adult Neurogenesis, and Pattern SeparationNeuron, 2011
- A role for hilar cells in pattern separation in the dentate gyrus: A computational approachHippocampus, 2008
- Minimal latency to hippocampal epileptogenesis and clinical epilepsy after perforant pathway stimulation‐induced status epilepticus in awake ratsJournal of Comparative Neurology, 2008
- The CA3 “backprojection” to the dentate gyrusProgress in Brain Research, 2007
- The dentate gyrus: fundamental neuroanatomical organization (dentate gyrus for dummies)Progress in Brain Research, 2007
- Stereological analysis of GluR2-immunoreactive hilar neurons in the pilocarpine model of temporal lobe epilepsy: Correlation of cell loss with mossy fiber sproutingExperimental Neurology, 2007
- The Hippocampus, Memory, and Place Cells: Is It Spatial Memory or a Memory Space?Neuron, 1999
- Relating Hippocampal Circuitry to Function: Recall of Memory Sequences by Reciprocal Dentate–CA3 InteractionsNeuron, 1999