# Projection Specific Modulation of Neural Activity with A Non-genetic Method

> **NIH NIH K01** · UNIVERSITY OF TEXAS AT AUSTIN · 2020 · $68,916

## Abstract

Project Summary
In psychiatry and neurology, there are many debilitating disorders based on aberrant circuits for which we do
not have adequate treatment methods. Recent developments in optogenetics and viral technology have
demonstrated that modulating the neural activity of specific projections in the brain is capable of rescuing
behavioral deficits, including those relevant to depression, autism and anxiety. However, this approach
requires genetic modification of neurons via viral transduction, which introduces a significant barrier for clinical
applications due to safety concerns. Also, the current projection-targeted neural modulation methods all use
visible light, limiting both the light penetration depth and the number of independent channels neuroscientists
can use for recording and modulating neural activity. Here, I would like to propose a non-genetic method
for projection-specific modulation of neural activity in freely behaving mammals. This approach will use
gold nanorods, a near-infrared (NIR) absorber and heat generation for neural modulations. Our preliminary
results have demonstrated that gold nanorods are internalized by neuron soma or axon terminals, are
transported retrograde/anterograde through neural axons and are sufficient to modulate neural activity under
NIR light after axon transport in vitro. The aim of this work is to continue the development of this approach from
in vitro to in vivo, which will be crucial for its future clinical translation. In Aim 1, I will determine the
internalization and axon transport of gold nanorods in vivo by characterizing brain slices with fluorescence
microscopy and electron microscopy. CLARITY will be used to visualize the nanoparticles in the whole
projection. The in vivo toxicity of gold nanorods will also be studied. In Aim 2, I will determine the mechanism of
photothermal modulation of neural activity by patching clamp, particularly the types of ions and ion channels
involved during the modulation process. I will also verify the conductions for in vivo modulation of neural
activity using fiber photometry. In Aim 3, I will examine the effectiveness of projection-specific modulation of
rodent behaviors with our developed gold nanorod methods in model circuits related to reward and anxiety.
The completion of the aims will result in the first non-genetic method for projection-targeted modulation of
neural activity. This method will complement optogenetic neural modulation and calcium imaging with an
orthogonal NIR channel and will present a better opportunity for clinical therapeutic applications due to its non-
genetic and non-viral nature. The work will be accomplished under a team of advisory members consisting of a
good balance of neuroscientists and nanomaterial experts: Dr. Karl Deisseroth, Dr. Sam Gambhir, Dr. Hongjie
Dai, Dr. Fan Yang and Dr. Talia Lerner. After the completion of the project, I will become proficient in various in
vivo techniques, such as optogenetics, fiber photo...

## Key facts

- **NIH application ID:** 10296391
- **Project number:** 7K01MH117490-04
- **Recipient organization:** UNIVERSITY OF TEXAS AT AUSTIN
- **Principal Investigator:** Huiliang Wang
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $68,916
- **Award type:** 7
- **Project period:** 2021-01-14 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10296391

## Citation

> US National Institutes of Health, RePORTER application 10296391, Projection Specific Modulation of Neural Activity with A Non-genetic Method (7K01MH117490-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10296391. Licensed CC0.

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