# The Role of Adult-born Dentate Granule Cells in Epileptogenesis

> **NIH NIH K08** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $201,735

## Abstract

PROJECT SUMMARY
 Nine percent of the population will experience a seizure at some point in their lifetime, but only a
fraction of these patients will develop epilepsy, a disease of recurrent unprovoked seizures. Understanding
why some patients have an increased propensity for seizures and how to reverse this tendency is essential.
More than a third of patients with epilepsy fail pharmacological therapy. Also while effective at decreasing
seizures, there is little evidence that these therapies have any effect on epileptogenesis. Moreover, current
diagnostic modalities lack the spatial resolution and specificity to accurately identify and treat brain areas
involved in epileptogenesis. Surgical treatments removing putative epileptic tissue can sometimes fail to
produce seizure freedom and can result in impairment of brain function. Thus, while significant progress has
been made in the treatment of epilepsy, limited knowledge regarding its pathogenesis has precluded the
development of more sophisticated therapies.
 Mesial temporal lobe epilepsy (mTLE) is the most common form of epilepsy in adults, and is
characterized by seizure activity and pathology within the medial temporal limbic regions, including the
hippocampal formation. Pathological changes in mTLE are particularly prominent in the dentate gyrus, a critical
node for controlling activity in the hippocampus, and one of only a two regions in the mammalian brain where
new neurons are born during adulthood. These newborn dentate granule cells make connections to other
neurons in the existing network, appear to be important for forming new memories, and undergo an number of
anatomical changes in mTLE. However, the function of newborn neurons and their role in hippocampal
function and epileptogenesis are not known.
 Studies in this grant will employ the use of novel deep two photon Ca2+ imaging techniques to explore
how newborn dentate granule cells recruit inhibitory neurons to quiet activity in the hippocampus, and how
seizures alter this process. These aims reflect my long-term career objectives to develop stem cell-based
therapies designed to quiet excitability and reverse epileptogenesis, as well as to engineer cells that express
optical reporters of neural activity in human epileptic patients. This mentored award will provide specific
advanced training in neural stem cells, experimental epilepsy models, and in vivo two-photon microscopy. This
training will be conducted under the direction of Dr. Fred Gage, a leader in neural stem cells and neurogenesis.
Drs. Tuszynski, Iragui, and Barba will provide additional mentoring in translational neuroscience and epilepsy,
and ensure that I remain on track for career advancement. Together we have formulated a detailed career
development plan providing training through regular mentor meetings, carefully selected coursework,
seminars, and hands-on research experience. The proposed research and career development plan will
benefit greatly from the intell...

## Key facts

- **NIH application ID:** 9960593
- **Project number:** 5K08NS093130-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Matthew Shtrahman
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $201,735
- **Award type:** 5
- **Project period:** 2016-07-15 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9960593

## Citation

> US National Institutes of Health, RePORTER application 9960593, The Role of Adult-born Dentate Granule Cells in Epileptogenesis (5K08NS093130-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9960593. Licensed CC0.

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