# Microphysiological System for the Human Hippocampal Dentate Gyrus-CA3 Circuit

> **NIH NIH R21** · JOHNS HOPKINS UNIVERSITY · 2020 · $230,963

## Abstract

Project Summary
To reduce the burden of neurological disease, induced pluripotent stem cell-derived human brain cells offer
the potential for unprecedented insight. But the capabilities of the nervous system arise from the interactions
of its cells, so to use them as a model of brain pathology, they must be investigated in a context where they
can reciprocally influence one another as they do in vivo. The field is in need of facsimiles with architectural
arrangements that recapitulate brain circuits.
To study the dentate gyrus-hippocampal CA3 circuit that is critical for memory and often altered in diseases
such as epilepsy, this project will place neuronal and glial precursor cells at precise locations. The project
consists of two aims. First, we will create a matrix suitable for capture of fluid droplets containing individual
glial and neuronal cells. This surface must be soft enough to minimize cell trauma during deposition and
must encourage the growth of these cells and extension of their processes. A porous scaffold constructed of
the brain extracellular component hyaluronic acid is the starting point for development of this capture
substrate. Embedding of signaling molecules will help specify cell identities and encourage cell growth, and
regional modulation of matrix properties will help guide cell organization.
Secondly, adapting methods from cell-sorting technology, we will develop a microfluidic system for optical
cell identification. When the droplet containing the cell is released, a charge is applied. As the droplet falls
through a voltage field, this charge determines its position. In this way cells will be deposited in precise
patterns.
The resulting array of neurons and glial cells will yield a robust, reproducible model -- composed of human
brain cells -- of neural circuit function and pathology. Given the great toll of neurologic diseases involving
hippocampus such as epilepsy, depression, and dementia, improved means of investigating these conditions
and possible treatments could benefit millions of individuals and families. Indeed, this project will provide a
framework for construction of a microphysiological system to model any brain circuit. This has potential to
yield significant value to public health.

## Key facts

- **NIH application ID:** 10057728
- **Project number:** 1R21NS114503-01A1
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** David W Nauen
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $230,963
- **Award type:** 1
- **Project period:** 2020-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10057728

## Citation

> US National Institutes of Health, RePORTER application 10057728, Microphysiological System for the Human Hippocampal Dentate Gyrus-CA3 Circuit (1R21NS114503-01A1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10057728. Licensed CC0.

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