# High Resolution Analysis of Redox Regulation in Dendrites

> **NIH NIH R21** · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · 2020 · $198,250

## Abstract

The remarkable functional range of the human brain emerges from interactions of myriad neuronal
filopodia that generate specific patterns of connectivity. This neuronal wiring during brain development
is shaped by sub-cellular spatial heterogeneity, such as dendritic `hot-spots' and filopodia. Even
adjacent filopodia of developing dendrites encounter distinct local micro-environments that alter their
fate. Consequently, many disease origins, including altered cognition, can be attributed to aberrant
behavior(s) of filopodia during brain wiring. A fundamental, unsolved question is how the local
environment modulates developing dendrites and how these interactions control dendritic fate, in
normal differentiation and in disease. We hypothesize that local redox state provides crucial context,
shaping neurite responses to signals. In particular, there is an unmet need for probing local regulators
of filopodia during the sculpting of the dendritic arbor. This proposal addresses this need by integrating
our expertise in cell signaling, the neurobiology of redox dynamics, and high-resolution imaging in
living cells with our expertise in designing and fabricating nanoliter micro-environments for low density
neuronal cultures. We will use microfluidic device (μFD) environments and high-resolution imaging of
fluorescent intracellular redox reporters to probe changes in localization, activity, and function of redox
signaling in developing hippocampal dendrites. We will use this system to map and influence redox
dynamics 1) in isolated, dendritic segments during their development, and 2) in their response to
semaphorin 3A, which has a dual nature as an axon repulsion cue and a promoter of dendrite growth. We
will gain new insights on how local redox dynamics in early developmental stages and in response to
Sema3A stimulation contribute to filopodia/dendritic maturation. These novel studies will address the
need for high resolution localization, regulation, and function of redox dynamics in developing
dendrites, a topic that has received little attention. This approach will provide fresh insights on this
putative regulator, new tools for studying regulation of redox-dynamics during dendrogenesis, and
contribute to developing effective strategies for restoring defects in affective disorders, Alzheimer's,
schizophrenia, Fragile X syndrome, autism, and chronic stress.

## Key facts

- **NIH application ID:** 9873994
- **Project number:** 5R21MH117377-02
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
- **Principal Investigator:** Martha U Gillette
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $198,250
- **Award type:** 5
- **Project period:** 2019-02-15 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9873994

## Citation

> US National Institutes of Health, RePORTER application 9873994, High Resolution Analysis of Redox Regulation in Dendrites (5R21MH117377-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9873994. Licensed CC0.

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