# Circuit reconstruction of functionally-identified neurons in deep brain regions: application to grid cells

> **NIH NIH F99** · PRINCETON UNIVERSITY · 2020 · $46,520

## Abstract

Project Abstract
Specialized synaptic wiring motifs have been suspected to be essential building blocks of cognition since the
birth of modern neuroscience. However the technology to test these ideas has been historically unavailable.
The grid cell system in medial entorhinal cortex (MEC), a deep brain area, is an exemplar of this problem. Grid
cells are essential for memory and navigation. They are thought to be key in the development of Alzheimer’s
disease. Yet the fundamental mechanisms underlying grid cell activity are not understood, owing to technical
barriers in assessing grid cells’ wiring patterns. Here I propose to overcome these barriers, by developing a
pipeline for circuit reconstruction of functionally-characterized neurons in deep brain areas. My dissertation
work thus far (Aim 1) has involved co-development of such a pipeline for surface brain areas, then adaptation
of this procedure for deep brain areas, using a combination of implantable optics, multiphoton calcium imaging
during behavior, electron microscopy, and multimodal techniques to register both functional and anatomical
data. During the independent phase (F99, Aim 2), I will apply this pipeline to grid cells in MEC, enabling
definitive refutation or confirmation of the wiring patterns predicted by current theories of grid cell function. I
then provide a postdoctoral plan (K00, Aim 3) for the creation of next-generation multiphoton imaging and
rodent behavioral technology. This postdoctoral training at the interface of optical design and engineering
methods aims to expand current capabilities for monitoring neural activity, reconstructing neural circuits, and
testing theories of brain function. Overall this proposal will enable me to develop skills in circuit reconstruction
and methods development for neuroscience, enhancing the probability of a career as an independent
investigator in academia. Finally, I anticipate that the proposed studies will advance technical capabilities for
neuroscience, and provide fundamental insight into the circuit architectures underlying memory and cognition
in a brain circuit highly relevant to pressing health needs.

## Key facts

- **NIH application ID:** 10009296
- **Project number:** 5F99NS115338-02
- **Recipient organization:** PRINCETON UNIVERSITY
- **Principal Investigator:** Alexander Riordan
- **Activity code:** F99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $46,520
- **Award type:** 5
- **Project period:** 2019-09-30 → 2021-09-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10009296

## Citation

> US National Institutes of Health, RePORTER application 10009296, Circuit reconstruction of functionally-identified neurons in deep brain regions: application to grid cells (5F99NS115338-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10009296. Licensed CC0.

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