Abdominal vagal pathways and their role in anxiety/affective state signalling: targeting vagus nerve stimulation

This project aims to determine whether specific abdominal vagal pathways can be targeted to influence anxiety-related behaviour, potentially providing a more selective alternative to conventional cervical vagus nerve stimulation (VNS). The vagus nerve is central to the gut-brain axis because it provides bidirectional communication between visceral organs and the brain, with approximately 80% of vagal fibres being sensory/afferent.

Conventional cervical VNS has limitations, particularly its relatively non-selective activation of mixed vagal fibres and associated adverse effects such as voice alterations, coughing and dyspnoea. Although VNS is clinically established for drug-resistant epilepsy and treatment-resistant depression, its mechanisms underlying behavioural effects remain incompletely understood.

The central hypothesis is that abdominal vagal pathways connecting the gut to the brain may contribute to emotional-state signalling, and that selective stimulation of these pathways could produce anxiolytic effects while reducing unwanted effects associated with cervical VNS.

The experimental approach compares four stimulation strategies: whole abdominal vagus stimulation, celiac branch stimulation, short intestinal segment stimulation, and long intestinal segment stimulation. These surgical interventions are followed by behavioural testing, histology, and sample collections for neurochemical and hormonal analysis.

Overall, the project seeks to identify anatomically selective gut-vagus pathways that regulate anxiety, with the longer-term goal of developing precision bioelectronic therapies.