# Investigating the vagal gut-brain circuit regulating hippocampal neurochemistry and neuroinflammation

> **NIH NIH F31** · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · 2022 · $37,619

## Abstract

Project Summary/Abstract:
The gut-brain axis, the bidirectional communication between the central nervous system (CNS) and enteric
nervous system, has become implicated in numerous pathologies in the CNS, many of which result in cognitive
impairments. Neuroinflammation has been identified as a critical mechanistic mediator of cognitive decline and
the gut-brain axis is emerging as an important regulator of peripheral and central inflammation. A chief
component of this immunomodulatory axis is the vagus nerve, as it mediates the cholinergic anti-inflammatory
network (CAIN) in both the CNS and periphery. Gastrointestinal (GI) vagal afferents extending from the GI tract
to the brain have been shown to activate the hippocampus, an essential integration center for learning and
memory. Accordingly, the goal of this study is to investigate the vagal gut-brain circuit regulating hippocampal
neurochemistry, neuroinflammation and cognition which remains poorly understood. This proposal utilizes a
highly innovative technique developed by my collaborator Dr. Guillaume de Lartigue that selectively ablates
~80% of GI vagal afferents with a saporin (SAP) toxin tagged with the GI hormone cholecystokinin (CCK). I will
then assess how impairing GI vagal afferents affects cholinergic neurochemistry and neuroinflammation in the
hippocampus with in vivo microdialysis, HPLC and biochemical assays. I will also assess the behavioral
consequences of GI vagal ablation with the novel object recognition task as Dr. de Lartigue has shown this
technique impairs hippocampal-dependent memory processes. To further elucidate this mechanism, I will then
assess if these hippocampal impairments can be rescued by a positive allosteric modulator (PAM) of α7
nicotinic acetylcholine receptors (nAChRs) as these receptors on the surface of macrophages, microglia and
astrocytes mediate the CAIN. Thus, the overarching hypothesis of this proposal is that positive allosteric
modulation of α7 nAChRs rescues hippocampal cholinergic deficits induced by the ablation of
gastrointestinal vagal afferents. Completion of these studies will provide insight into the immunoregulatory
actions of the gut-brain axis and the integral role this relationship plays in various CNS disorders, especially
those with neuroinflammation and cognitive impairments. In addition, this project provides me ample
opportunities to diversify my technical skills with a team of mentors who are experts in their fields and have a
strong history of collaboration and federal funding. This strong mentorship team also provides extensive
networking and dissemination opportunities that will shape me into a productive, independent researcher.

## Key facts

- **NIH application ID:** 10534301
- **Project number:** 1F31DK131773-01A1
- **Recipient organization:** UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA
- **Principal Investigator:** HANNAH Burzynski
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $37,619
- **Award type:** 1
- **Project period:** 2022-05-31 → 2024-05-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10534301

## Citation

> US National Institutes of Health, RePORTER application 10534301, Investigating the vagal gut-brain circuit regulating hippocampal neurochemistry and neuroinflammation (1F31DK131773-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10534301. Licensed CC0.

---

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