Abdominal vagal pathways and their role in anxiety/affective signalling targeting vagus nerve stimulation (VNS)

• Professor John Furness & Dr Pratik Thakkar

  Project supervisors

  j.furness@unimelb.edu.au, pratik.thakkar@unimelb.edu.au
  

Project Details

The 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 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.

Researchers

Dr Pratik Thakkar, Professor John Furness, Mr Scott Carter, Dr Myat Noe (Cherish) Han

Collaborators

Dr Suzzane Truong, Dr Hieu Le, A/Prof Sam John, A/Prof Jeremy Cottrell

Research Opportunities

This research project is available to PhD students, Masters by Research, Honours students, Master of Biomedical Science, Post Doctor Researchers to join as part of their thesis.
Please contact the Research Group Leader to discuss your options.

Research Publications

1. Payne, S. C., Furness, J. B., & Stebbing, M. J. (2019). Bioelectric neuromodulation for gastrointestinal disorders: effectiveness and mechanisms. Nat Rev Gastroenterol Hepatol, 16(2), 89–105. doi: 10.1038/s41575-018-0078-6.
2. Felippe, I. S. A., Babbage, T. L., Shaheen, R., Bassetto, M., Fan, J.-L., Pauza, A., Gold, O., Thakkar, P., Dawes, M., Bates, M. L., McBryde, F., Fountain, S. J., Fisher, J. P., & Paton, J. F. R. (2026). Vitamin B6 (Pyridoxal 5′ Phosphate) antagonises carotid body P2X3 receptors in hypertension. Cardiovascular Research, 122(2), 285-296, doi: 10.1093/cvr/cvaf195
3. Gogoi, A., Babu, M., Gangadhar, A., Shirin, R., Thomas, D. A., Jayaram, J., Thakkar, P., & Datta, A. (2026). Proteomics of In Vivo models of ischemic stroke: A systematic review with a systems biological perspective. Ageing Research Reviews, 113, 102937, doi: 10.1016/j.arr.2025.102937
4. Shen, X., Pauza, A. G., Gold, O. M. S., Felippe, I. S. A., Thakkar, P., & Paton, J. F. R. (2026). Glomus cell heterogeneity underpins distinct carotid body chemoreflex pathways: implications for hypertension. Cardiovascular Research, 122(10), 1391-1407, doi:10.1093/cvr/cvag118
5. Thakkar, P., & Parihar, A. (2026). Heart Failure in Cystic Fibrosis: Treatment and Prognosis. Cystic Fibrosis: Disease Management and Advanced Drug Delivery Systems. doi: 10.1201/9781779640413-14