# Investigation of an Optogenetic Vagus Nerve Stimulation Device in an Animal Model of Post-traumatic Stress Disorder

> **NIH VA I21** · VA EASTERN COLORADO HEALTH CARE SYSTEM · 2024 · —

## Abstract

The proposed research will develop a novel system for optogenetic vagus nerve stimulation and investigate the
impact of vagal stimulation in a rodent model of post-traumatic stress disorder (PTSD).
Therapeutic interventions using peripheral nerves of the autonomic nervous system are increasingly being
considered and applied to modulate organ function for disease treatments. Vagus nerve stimulation (VNS) has
been clinically approved for over two decades for its treatment of epileptic seizures and depression. It has also
demonstrated positive clinical outcomes in the treatment of inflammatory disorders such as rheumatoid arthritis
and Crohn’s disease, while clinical and pre-clinical data suggest therapeutic benefit in heart disease and
diabetes. Cholinergic (parasympathetic) pathways of the vagus nerve are an important factor in the
therapeutic effects that are observed. The ‘cholinergic anti-inflammatory pathway’ is an established signaling
mechanism by which the expression and release of pro-inflammatory cytokines are reduced in the spleen and
in other visceral tissues. Because inflammation is a driver of numerous diseases, the ability to regulate
inflammatory mediators is of major interest. In state-of-the-art electrical vagus nerve stimulation (VNS),
however, current is applied broadly to the nerve and the non-specific nature of this stimulation activates off-
target pathways causing adverse effects to the patient, and furthermore, does not provide adequate precision
to study and understand therapeutically relevant nerve pathways. The proposed research will develop and
apply an optogenetic system for vagus nerve stimulation that can eliminate these off-target complications.
With optogenetic tools, light-sensitive actuators can be targeted to cell-types of interest via genetic targeting
and tissue-specific viral delivery, thus enabling highly specific activation and investigation of neural circuits.
This neuromodulation methodology will be applied to PTSD, a highly prevalent burden among the U.S. Veteran
population. PTSD is highly correlated with elevated inflammation and often co-morbid with many of the
diseases mentioned above. In addition to the anti-inflammatory pathways of the vagus nerve, beneficial
impacts observed in psychiatric and inflammatory disorders suggest that vagal stimulation may be effective in
treating PTSD, and indeed, VNS in rodent models enhances fear extinction and reduces anxiety. The current
study will develop a 3D-printed vagus nerve cuff system for optogenetic studies (Aim 1). This biocompatible,
single-component, optical stimulation nerve implant will enable an easy-to-fabricate and easy-to-implant device
for chronic stimulation. The effectiveness and longevity of the system will be validated by assessing cardiac
responsivity longitudinally in surgically implanted mice (Aim 2), before testing the system in a PTSD mouse
model (Aim 3). A previously described single electric footshock protocol will be used to condition ...

## Key facts

- **NIH application ID:** 11064757
- **Project number:** 5I21RX003894-03
- **Recipient organization:** VA EASTERN COLORADO HEALTH CARE SYSTEM
- **Principal Investigator:** Arjun K Fontaine
- **Activity code:** I21 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2022-05-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11064757

## Citation

> US National Institutes of Health, RePORTER application 11064757, Investigation of an Optogenetic Vagus Nerve Stimulation Device in an Animal Model of Post-traumatic Stress Disorder (5I21RX003894-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11064757. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*