# Cellular and Circuit Mechanisms of Temporal Lobe Epilepsy

> **NIH NIH R01** · DUKE UNIVERSITY · 2021 · $405,383

## Abstract

Epilepsy arising from the temporal lobes is particularly devastating because it is both common and commonly
resistant to symptomatic therapy with anticonvulsants. Preclinical and clinical studies support the idea that an
episode of status epilepticus followed by recovery contributes to development of temporal lobe epilepsy months
or years later. Insight into the mechanisms by which status epilepticus induces temporal lobe epilepsy may
facilitate developing preventive and/or disease modifying therapies. We recently discovered a molecular
signaling pathway by which status epilepticus induces temporal lobe epilepsy, namely activation of the brain-
derived neurotrophic factor receptor, TrkB. A major unresolved question, to be addressed in this application,
is how this signaling is transformed into the cellular and circuit modifications that underlie temporal lobe
epilepsy. The anatomic locale at which status epilepticus induced activation of TrkB provides a valuable clue
to the cellular consequences. The principal site was the synaptic boutons of the mossy fiber axons of
hippocampal dentate granule cells. The objective of this application is to test three facets of our unifying
hypothesis: a) that status epilepticus induces plasticities of mossy fiber synapses with both CA3 pyramidal
cells and inhibitory interneurons; b) that status epilepticus induction of these plasticities requires TrkB; and c)
that transmitter release from the mossy fibers underlies expression of temporal lobe epilepsy.

## Key facts

- **NIH application ID:** 10101695
- **Project number:** 5R01NS097717-05
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** James O. McNamara
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $405,383
- **Award type:** 5
- **Project period:** 2017-02-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10101695

## Citation

> US National Institutes of Health, RePORTER application 10101695, Cellular and Circuit Mechanisms of Temporal Lobe Epilepsy (5R01NS097717-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10101695. Licensed CC0.

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