# Normal and Pathological Function of the Dentate Gyrus

> **NIH NIH R01** · CHILDREN'S HOSP OF PHILADELPHIA · 2020 · $367,500

## Abstract

The dentate gyrus serves as a critical regulatory entry point to the hippocampus, translating the
highly active coding language of medial entorhinal cortical neurons to the distinct, sparse
encoding that is characteristic of hippocampal function. This dentate gyrus-mediated translation
is vital to many aspects of information processing in the CNS. The underlying circuit
mechanisms responsible for this activity level transformation within the dentate gyrus are largely
unknown, but local circuit inhibitory neurons are hypothesized to play an important role. The
dentate gyrus also functions to regulate pathological activation of the limbic system, restricting
relay of aberrant activity from the entorhinal cortex to the hippocampus. Loss of this filter or
gating function could contribute to the generation of seizures, the hallmark of epilepsy. In this
proposal, we will utilize state of the art imaging, patch clamp, chemogenetic, and transgenic
techniques to test the hypotheses that that the sparse firing properties characteristic of dentate
granule cells are generated within the local circuit, and that degradation in these mechanisms
contributes both to seizure predisposition and cognitive comorbidities characterizing epilepsy.
We propose to determine the cellular properties that mediate dentate granule cell activation,
learn the identity of interneurons responsible for the control of dentate granule cell activation,
study the mechanisms responsible for degradation in granule cell sparse firing in epileptic
animals, and finally, restore normal cognitive function in animals with epilepsy using
chemogenetic manipulation of granule cell firing levels. We know little about the mechanisms
mediating the firing properties of neurons in the hippocampal dentate gyrus responsible for
information coding, and even less about how epilepsy may erode this critical aspect of the
cognitive functions emerging from the hippocampus. In addition to seizures, patients with
epilepsy exhibit severe deficits in learning and memory. Understanding how epilepsy
development alters circuit properties within the limbic system may be important not only in
targeting new therapies for seizure amelioration, but also in developing new treatments to
reduce comorbid conditions accompanying epilepsy development.

## Key facts

- **NIH application ID:** 9922994
- **Project number:** 5R01NS082046-09
- **Recipient organization:** CHILDREN'S HOSP OF PHILADELPHIA
- **Principal Investigator:** DOUGLAS A COULTER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $367,500
- **Award type:** 5
- **Project period:** 2012-09-01 → 2022-04-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9922994

## Citation

> US National Institutes of Health, RePORTER application 9922994, Normal and Pathological Function of the Dentate Gyrus (5R01NS082046-09). Retrieved via AI Analytics 2026-06-05 from https://api.ai-analytics.org/grant/nih/9922994. Licensed CC0.

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