Previous studies have suggested that mossy cells are lost from the neuronal circuit of the dentate gyrus after various epiletogenic insults, and has given rise to the widely accepted, although often questioned, so called """"""""dormant basket cell"""""""" hypothesis of epileptogenesis. In the previous award made to Dr. Soltesz he has set out to comprehensive challenge and explore at a cellular and synaptic level each element of the dentate-gyrus-hippocampal circuit to explore what elements are directly and indirectly impacted in a model of fluid percussion head trauma. This competitive renewal turns the focus of the study to the principal hilar neuron the """"""""mossy cell"""""""" and proposes a rather straightforward set of experiments to disprove the """"""""dormant basket cell hypothesis"""""""" and demonstrate that instead of being lost in models of epileptogenesis, significant numbers of mossy cells persist following percussive head trauma and contribute to an increased hyperexcitability by entering into a increased recurrent excitation of dentate gyrus granule cells which in turn feedback to both inhibitory interneurons and hilar mossy cells to increase hippocampal excitability and the resultant epileptogenic activity.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS035915-07
Application #
6621871
Study Section
Special Emphasis Panel (ZRG1-BDCN-3 (02))
Program Officer
Fureman, Brandy E
Project Start
1997-06-01
Project End
2005-05-31
Budget Start
2003-06-01
Budget End
2004-05-31
Support Year
7
Fiscal Year
2003
Total Cost
$285,760
Indirect Cost
Name
University of California Irvine
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
046705849
City
Irvine
State
CA
Country
United States
Zip Code
92697
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Szabo, Gergely G; Du, Xi; Oijala, Mikko et al. (2017) Extended Interneuronal Network of the Dentate Gyrus. Cell Rep 20:1262-1268
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Bui, Anh D; Alexander, Allyson; Soltesz, Ivan (2017) Seizing Control: From Current Treatments to Optogenetic Interventions in Epilepsy. Neuroscientist 23:68-81
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Bezaire, Marianne J; Raikov, Ivan; Burk, Kelly et al. (2016) Interneuronal mechanisms of hippocampal theta oscillations in a full-scale model of the rodent CA1 circuit. Elife 5:
Krook-Magnuson, Esther; Soltesz, Ivan (2015) Beyond the hammer and the scalpel: selective circuit control for the epilepsies. Nat Neurosci 18:331-8
Lee, Sang-Hun; Ledri, Marco; Tóth, Blanka et al. (2015) Multiple Forms of Endocannabinoid and Endovanilloid Signaling Regulate the Tonic Control of GABA Release. J Neurosci 35:10039-57
Bui, Anh; Kim, Hannah K; Maroso, Mattia et al. (2015) Microcircuits in Epilepsy: Heterogeneity and Hub Cells in Network Synchronization. Cold Spring Harb Perspect Med 5:

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