Astrocyte-Driven Modulation of Whole-Brain Functional Networks and BOLD Signals Revealed by Optogenetic-fMRI

Zhuang Liu1  · Li Wang2  · Tiangang Lou3  · Ziyue Zhao1,4 · Hongying Du5  · Juxiang Chen6  · Hongchun Zeng1  · Jie Wang1,7  · Kun Wang3

1 Department of Ultrasonography, Songjiang Research Institute, Shanghai Key Laboratory of Emotions and Affective Disorders, Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China 

2 School of Medicine, Jingchu University of Technology, Jingmen 448000, China 

3 Department of Anesthesiology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China 

4 State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences, Wuhan 430071, China 

5 Department of Food Science and Engineering, College of Light Industry and Food Engineering, Nanjing Forestry University, Nanjing 210037, China 

6 Department of Neurosurgery, Changhai Hospital, Naval Medical University, Shanghai 200082, China 

7 Institute of Neuroscience and Brain Diseases, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang 441021, China

Abstract

Astrocytes have long been considered passive players in brain function, yet emerging evidence suggests they actively modulate neural activity and signal transmission. This study combines chemogenetics and optogenetics approaches with functional magnetic resonance imaging (fMRI) to investigate the impact of astrocyte activation on local field potentials (LFPs) and downstream BOLD signals. Using a multimodal neuroimaging approach, we explore how astrocyte activation influences electrophysiological responses in different brain regions, particularly focusing on the prefrontal cortex (PFC) and its downstream targets. Our results reveal significant increases in LFP energy within specific frequency bands, such as Theta and Delta, in response to laser stimulation. These changes demonstrate the spatial specificity of astrocyte activity and its capacity to modulate local network dynamics. Furthermore, following chemogenetic inhibition of neuronal activity, optogenetic reactivation of astrocytes continued to evoke BOLD responses, supporting the notion that astrocytes have a pivotal role in the regulation of cerebral blood flow and metabolism. These findings challenge traditional views of BOLD signal origins and emphasize the need for a reevaluation of astrocyte involvement in neurovascular coupling. This study provides novel insights into astrocyte function, offering a new perspective on brain-wide connectivity and its implications for both normal brain function and neuropathological conditions.

Keywords

Astrocytes; Blood oxygen level dependent (BOLD); Local field potentials (LFPs); Prefrontal cortex (PFC); Chemogenetic/optogenetic approach

[SpringerLink]