# Novel optogenetic tool for noninvasive neuronal inhibition

> **NIH NIH R21** · UNIVERSITY OF WYOMING · 2022 · $180,625

## Abstract

PROJECT SUMMARY/ ABSTRACT
This exploratory bioengineering project is aimed at designing, building and testing a light-activated glutamate
decarboxylase (GAD) as a novel optogenetic tool for noninvasive inhibition of neuronal activity. GAD produces
gamma-aminoburyric acid, GABA, a central neurotransmitter involved in reducing neuronal excitability. Enzy-
matic activity of the engineered enzyme will be controlled by light in the near-infrared window (NIRW) of the
spectrum (670-900 nm) that penetrates through the skull and brain tissue much better than visible light. We
expect the NIRW light-activated GAD (NIRW-GAD) expressed in specific brain regions to be activated via ex-
tracorporeal light (e.g., transcranially). NIRW-GAD will represent a unique optogenetic research tool for nonin-
vasive, spatiotemporally controlled long-term inhibition of neuronal activity in deep or surface brain regions. In
the future, it may be developed into a gene therapy for neurological and psychiatric disorders involving hyper-
active brain, such as epilepsy, schizophrenia, anxiety and autism spectrum disorder. The NIRW-GAD protein
will be engineered using the homodimeric bacteriophytochrome engineering approach, where bacteriophyto-
chromes are a class of photoreceptors that sense light within the NIRW spectrum. In Aim 1, the NIRW-GAD
prototypes will be designed and screened for light-inducible GAD activity in yeast. The dynamic range and back-
ground activity of the enzyme will be optimized using mutagenesis. In Aim 2, we will examine the NIRW-GAD
expression and the effects of NIRW treatment in the somatosensory cortex neurons of mice. We will also quantify
the effect of NIRW-GAD on GABAergic synapses and GABA quantal content in cortical neurons in vitro. Upon
completion of this project, we expect to have engineered and tested a unique optogenetic tool for noninvasive
control of the major inhibitory neurotransmitter in silencing of neuronal activity in mammals.
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## Key facts

- **NIH application ID:** 10353090
- **Project number:** 1R21EB032609-01
- **Recipient organization:** UNIVERSITY OF WYOMING
- **Principal Investigator:** Mark Gomelsky
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $180,625
- **Award type:** 1
- **Project period:** 2022-09-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10353090

## Citation

> US National Institutes of Health, RePORTER application 10353090, Novel optogenetic tool for noninvasive neuronal inhibition (1R21EB032609-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10353090. Licensed CC0.

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