# Development of Light Triggered Molecular Tools Critical for Understanding the Brain's Network

> **NIH NIH R15** · FLORIDA INSTITUTE OF TECHNOLOGY · 2020 · $411,630

## Abstract

Development of Light Triggered Molecular Tools
 Critical for Understanding the Brain's Network
 PI: Nasri Nesnas, PhD
 PROJECT SUMMARY
Brain disorders, such as dementia, epilepsy, and depression, continue to be a major challenge in
medicine. This is not surprising considering the enormous complexity of the brain's network of
neurons. An average human brain incorporates nearly 86 billion neurons intertwined with as many as
10,000 synaptic connections. Such complexity is far more colossal than any computer processor or
even the entire worlds' road maps. Therefore, brain-mapping efforts have become of apparent
urgency to enable a better understanding of this complex maze.
Making substantial advances in this area certainly requires collaboration of multiple disciplines. Light
responsive molecular tools have become indispensible to neuroscientists as they provide means to
manipulate specific neuronal connections with precise timing. We established collaborations with
several neuroscientists, including Attila Losonczy of Columbia University and James Schummers of
Florida International University (FIU), to design and use these critical tools. Recent advances in
neuroscience led to the development of genetically engineered GPCR and LGIC receptors (DREADD
and PSAM, respectively), which can be introduced into a select population of neurons. These
receptors can be controlled with high specificity by loyal (inactive to other receptors) synthetic drugs
to enable studying animal behavior in vivo. However, there are currently no means to precisely
control the timing of delivery of these drugs as they are injected or administered orally.
Photocleavable protecting groups, also known as cages, enable the release of active agonists with
light. The principal advantage of this technique is the unparalleled precision of activation in location
as well as timing, otherwise referred to as spatio-temporal control. We have prepared several of
these cages, and we aim to design more efficient ones that can also respond in visible and near IR
wavelengths to avoid photo toxicities associated with UV light traditionally used. We also aim to use
these longer wavelength chromophores to cage DREADD and PSAM molecules to enable their
activation with precise timing. This would present a technique that incorporates advantages of both
optogenetics as well as chemogenetics. Preparation of effective photoactive molecular tools will
directly benefit the larger neuroscience community in studying the brain with the level of detail
essential to treating elusive brain disorders.
I will continue to actively engage undergraduate students in these endeavors, and particularly
emphasize the diversity of educational and cultural backgrounds of the members in my research lab.
I have been successful at maintaining a larger percentage of female students than our university's
average and I will continue to do so as well as encouraging minority students to engage in research.

## Key facts

- **NIH application ID:** 9964106
- **Project number:** 2R15GM112119-02
- **Recipient organization:** FLORIDA INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Nasri Nesnas
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $411,630
- **Award type:** 2
- **Project period:** 2015-09-22 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9964106

## Citation

> US National Institutes of Health, RePORTER application 9964106, Development of Light Triggered Molecular Tools Critical for Understanding the Brain's Network (2R15GM112119-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9964106. Licensed CC0.

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