# Mossy cell control of adult neurogenesis in epilepsy

> **NIH NIH F32** · OREGON HEALTH & SCIENCE UNIVERSITY · 2020 · $65,310

## Abstract

Epilepsy results from an imbalance in neuronal excitation and inhibition within the brain. One of the most
common forms of epilepsy is temporal lobe epilepsy (TLE), and a large percentage of TLE patients are
refractory to medical treatment. TLE is associated with cell loss, gliosis, altered neurogenesis, axon sprouting,
and synaptic reorganization in both humans and animal models of TLE. These changes are best described in
the hippocampus, which becomes hyperexcitable in epilepsy and can serve as an initiating seizure focus in
TLE. In rodent models, there is increased proliferation of adult-born neurons in the hippocampus in TLE, and
these new neurons integrate abnormally into neuronal circuits and are believed to contribute to
epileptogenesis. Glutamatergic signaling and synapse formation are critical for the proper maturation, synaptic
integration, and survival of adult-born dentate granule cells (DGCs), and a recent study demonstrated that hilar
mossy cells serve as the first glutamatergic inputs to adult-born DGCs. Interestingly, these hippocampal mossy
cells are also highly susceptible to apoptosis after seizures. This suggests that the loss of mossy cells after
status epilepticus could alter the maturation and synapse formation by adult-born DGCs and thus the loss of
these cells may be a critical step in pathogenesis of epilepsy via its effect on post-seizure neurogenesis. This
proposal will investigate how mossy cells contribute to the normal maturation and network integration of adult-
born granule cells, and whether mossy cell loss contributes to the abnormal synaptic integration, maturation,
and survival of adult-born DGCs in epilepsy. In addition, we will directly test whether the rescue of mossy cell
loss prevents alterations in neurogenesis and the development of epilepsy. We will use a mossy cell specific
Cre driver mouse line to selectively modify mossy cell activity and survival using pharmacogenetics, diphtheria
toxin-mediated cell ablation, and inhibition of apoptosis, and assess changes in adult-born DGC synaptic
integration and survival. Additionally, we will combine these techniques with the well-established pilocarpine
model of TLE, to assess how mossy cell death affects adult-born DGC maturation and epileptogenesis. We
hypothesize that mossy cell activity is critical for proper integration, maturation, and survival of adult-born
granule cells and that a reduction in mossy cell loss will restore these features and reduce epileptogenesis
after status epilepticus in mice. This study will not only greatly improve our understanding of the role of mossy
cells in neurogenesis and epilepsy, but could lead to the development of new therapeutic strategies for many
types of refractory epilepsies.

## Key facts

- **NIH application ID:** 9912852
- **Project number:** 5F32NS106732-03
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** CORWIN BUTLER
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $65,310
- **Award type:** 5
- **Project period:** 2018-05-01 → 2021-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9912852

## Citation

> US National Institutes of Health, RePORTER application 9912852, Mossy cell control of adult neurogenesis in epilepsy (5F32NS106732-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9912852. Licensed CC0.

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