# Noninvasive low-intensity focused ultrasound-enabled sonogenetic method to induce plasticity in adult visual cortex.

> **NIH NIH R21** · JOHNS HOPKINS UNIVERSITY · 2020 · $395,731

## Abstract

PROJECT SUMMARY
 Development of non-invasive tools for activating deep brain structures is critical for causally
manipulating neural function in humans. Furthermore, such method, if able to elicit long-term plastic changes in
neural circuits, will aid in functional recovery of neural function. One of the promising non-invasive neural
modulation technique that has a potential to activate deep brain structures in a focal manner is ultrasound.
Several groups have demonstrated that ultrasound can lead to neural activation, alter sensory responses, or
cause behavioral outcomes. In this proposal, we aim to fill a gap in knowledge as to whether focal stimulation
of deep brain structures using Low Intensity Focused Ultrasound (LIFU) leads to long-term changes in neural
function relevant for functional recovery, especially in the adult brain with limited capacity for plasticity. It is
known that the developmental loss of thalamocortical (TC) plasticity precedes the closure of the critical period
for cortical plasticity in sensory cortices, which suggests that recovery of TC plasticity may be needed to
restore plasticity in the adult brain. In line with this idea, several studies have reported that recovery of adult
cortical plasticity is often accompanied by restoration of TC plasticity. A previous study demonstrated that
patterned electrical stimulation of the visual thalamus (dLGN) produces long-term potentiation (LTP) of TC
inputs to the primary visual cortex (V1) in adult rats. Here we will investigate whether non-invasive LIFU
stimulation of dLGN can produce TC plasticity in adult V1. In Aim 1, we will determine whether LIFU stimulation
leads to long-term plastic changes of dLGN inputs to layer 4 (L4) of adult V1. To do this, we will use a LIFU
stimulation device developed by the Applied Physics Laboratory (APL) at Johns Hopkins University, and
combine this with genetic tools to express exogenous genes specifically in activated dLGN neurons.
Specifically, we will use genetic methods that can drive the expression of optogenetic tools (i.e.
channelrhodopsin-2) selectively to LIFU-stimulated neurons to functionally assess long-term synaptic plasticity,
and test the utility of a novel sonogenetic tool that can provide cell-type specificity to LIFU stimulation. In Aim 2,
we will investigate whether LIFU stimulation can alter neural response properties of V1 L4 neurons using in
vivo 2-photon Ca2+ imaging. Results from our study will determine whether LIFU stimulation can produce long-
term plasticity of neural circuits in the adult brain, which can be relevant for designing non-invasive methods for
functional recovery. At the very least, our study will provide genetic methodologies that can drive exogenous
gene expression in deep brain structures using LIFU stimulation, and will provide information on whether
sonogenetics can produce cell-type specific activation of deep brain structures.

## Key facts

- **NIH application ID:** 9924788
- **Project number:** 1R21EY031265-01
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Grace M Hwang
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $395,731
- **Award type:** 1
- **Project period:** 2020-05-01 → 2022-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9924788

## Citation

> US National Institutes of Health, RePORTER application 9924788, Noninvasive low-intensity focused ultrasound-enabled sonogenetic method to induce plasticity in adult visual cortex. (1R21EY031265-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/9924788. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*