# Interrogation of dopaminergic activity using non-invasive ultrasound

> **NIH NIH R21** · STANFORD UNIVERSITY · 2022 · $237,964

## Abstract

Dysfunction of dopaminergic signaling is a common denominator of substance abuse disorders. Based
on this premise, specific modulation of mesocorticolimbic dopaminergic neurons in the ventral
tegmental area (VTA) has been at the focus of interventions to treat substance abuse. However, a non-
invasive, precise and reliable method that targets dopaminergic neurons has not been developed yet
as an alternative to pharmacological treatment. Focused ultrasound is emerging as an alternative non-
invasive method to transcranial magnetic stimulation and deep brain stimulation. Ultrasound is able to
penetrate the skull and transducers may be designed to steer sound waves to any area of the brain.
However, a major limitation of focused ultrasound has been the inability to determine the effect of
pressure waves on the activity of specific cell types in behaving animals. We have developed a new
device that combines a lightweight piezoelectric ring transducer that can be mounted on the mouse’s
skull, and an optical fiber to monitor neuronal activity by means of fluorescent signals from a calcium
biosensor (e.g. GCamp7). Preliminary studies in the hippocampus and in the VTA indicate that there
are combinations of parameters of ultrasound (i.e. intensity, carrier frequency, pulse frequency and
duration) that result in differential stimulation or inhibition of excitatory and inhibitory neurons. Here we
plan to use this new device to interrogate the effect of ultrasound on dopaminergic neuronal activity in
the VTA. We will determine an optimal set of parameters that differentially stimulate dopaminergic VTA
neurons compared to adjacent GABA neurons. In parallel, we will validate conditions that result in
ultrasound-elicited conditioned place preference or aversion. The result of these experiments will
dramatically advance our understanding of the effect of ultrasound on brain reward circuits, and may
lead the path for intervention of the dopaminergic system in patients suffering from substance abuse
disorders.

## Key facts

- **NIH application ID:** 10467409
- **Project number:** 1R21DA055056-01A1
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Luis De Lecea
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $237,964
- **Award type:** 1
- **Project period:** 2022-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10467409

## Citation

> US National Institutes of Health, RePORTER application 10467409, Interrogation of dopaminergic activity using non-invasive ultrasound (1R21DA055056-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10467409. Licensed CC0.

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