# Genetically-Encoded, Non-Invasive and Wireless Modulation of Calcium Dynamics in Astrocytes With Spatiotemporal Precision and Depth

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA BERKELEY · 2023 · $784,131

## Abstract

Abstract
Astrocytes are the most abundant cell types in the brain and have long been thought as primarily passive support
cells. Studies in the past two decades leveraging modern techniques have revealed crucial roles for astrocytes
in neuronal circuit assembly, synaptic function and behavior. Aberrant astrocytic function is implicated in
neuropsychiatric and neurodegenerative diseases, and astrocytes hold great promises as novel therapeutic
targets for improving treatment efficacy. Despite this progress, a deeper mechanistic understanding of
astrocytes' causative and correlative roles in operating neural circuitry and their contribution to behavior is still
lacking. This knowledge gap is largely due to the lack of technologies to effectively manipulate astrocyte activity
with cell-type and temporal precision. The physiological hallmark of astrocytes is their complex spatiotemporal
patterns of intracellular and intercellular calcium signaling crucial to their bidirectional interaction with neurons.
The objective of this project is to develop a non-invasive, wireless and genetically encoded actuator to modulate
astrocytic activity with cell-type and temporal precision in vivo. Our approach, named FeRIC (Ferritin iron
Redistribution to Ion Channels), combines the use of radiofrequency (RF) waves and ion channels to control
membrane ion permeability non-invasively and wirelessly. The FeRIC technique utilizes RF waves to activate
membrane proteins that are coupled to the endogenous cellular iron storage protein ferritin. Our preliminary
studies have demonstrated the feasibility of FeRIC-mediated RF stimulation to modulate calcium activities in
astrocytes and astrocytic networks that resembles those observed under physiological conditions. Further,
FeRIC-mediated RF stimulation of astrocytes has been able to elicit neurotransmitter release and evoke action
potentials in connected neurons. We aim to develop a set of molecular tools and characterize their abilities 1) to
modulate global calcium signaling in astrocytes, 2) to modulate microdomain calcium activities in astrocytes and
3) to modulate astrocyte-neuron interactions at the tripartite synapses in vivo. If successful, the project will
develop a non-invasive and genetically encoded molecular tool to modulate astrocytic activity with cell-type and
temporal precision. We will elucidate the biophysical underpinnings of the mechanism. The project will have a
broad impact to the study of the roles of astrocytes in health and disease.

## Key facts

- **NIH application ID:** 10562265
- **Project number:** 1R01NS129888-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Chunlei Liu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $784,131
- **Award type:** 1
- **Project period:** 2023-02-01 → 2028-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10562265

## Citation

> US National Institutes of Health, RePORTER application 10562265, Genetically-Encoded, Non-Invasive and Wireless Modulation of Calcium Dynamics in Astrocytes With Spatiotemporal Precision and Depth (1R01NS129888-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10562265. Licensed CC0.

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