Divergent Behavioral and Circuit-Level Adaptations to Acute and Chronic Gastric Electrical Stimulation

Area of Science:

• Neuroscience
• Gastroenterology
• Bioelectronics

Background:

• Anxiety disorders are common and difficult to treat, driving research into new neuromodulatory strategies.
• Vagus nerve stimulation (VNS) shows that targeting the gut-brain axis can influence emotional circuits.
• Gastric electrical stimulation (GES) is used for GI motility disorders, but its effect on anxiety is unknown.

Purpose of the Study:

• To investigate the effects of GES on anxiety-related behavior in rodents.
• To identify the neural pathways modulated by GES.
• To establish a model for chronic gastric neuromodulation in freely moving animals.

Main Methods:

• Developed a chronic, untethered gastric stimulation platform for freely moving rats.
• Used cross-species whole-brain activity mapping (c-Fos) in mice to study neural mechanisms.
• Employed behavioral tests (open field, elevated plus maze) with machine learning for analysis.

Main Results:

• Acute GES induced anxiety-like behavior (reduced exploration, increased freezing) in novel environments.
• Chronic GES led to enhanced exploratory behavior, indicating temporally dynamic effects.
• Stimulation modulated limbic-cortical networks, including the entorhinal cortex, nucleus tractus solitarii, amygdala, and hippocampus.

Conclusions:

• GES has temporally dynamic and context-sensitive effects on anxiety-like behavior.
• The stomach serves as a peripheral access point for modulating central emotional circuits.
• This study provides systems-level validation for gastric neuromodulation in anxiety treatment.