# Understanding Modulation of Neuronal Subpopulations by Sympathetic Glia

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2024 · $102,307

## Abstract

PROPOSAL
ABSTRACT OF FUNDED GRANT
 Cardiac injury predisposes patients to heart failure (HF), and ventricular
tachycardia/fibrillation (VT/VF). Development of HF and VT/VF after cardiac injury is tightly
linked to sympathetic neural remodeling. Although several medications targeting cardiac
sympathetic excess reduce mortality following cardiac injury, significant shortcomings of these
drugs include off-target effects, limited efficacy, and focus on downstream consequences of
neural remodeling such as excess catecholamine release, rather than preventing it upstream. In
this proposal, we build on strong preliminary data from humans, porcine, and murine models
demonstrating that satellite glial cell (SGC) activation is a central feature of chronic cardiac
injury. Activated glia release inflammatory cytokines, ATP, and other factors that modulate
neuronal function. Chemogenetic upregulation of glial calcium signaling (as observed in
activated glia) increase cardiac sympathetic neuronal excitability, synaptic efficacy, and tonic
firing. Based on these novel findings, the goal of this proposal is to test the hypothesis that
satellite glial activation and enhanced glial-neuronal signaling is a primary driver of cardiac
sympathetic neuronal dysfunction, HF and VT/VF after cardiac injury. We will test our
hypotheses using novel tools from a multidisciplinary team of investigators in 3 specific aims in
two murine models of cardiac injury (ischemia-reperfusion and dilated cardiomyopathy). We will
test whether following cardiac injury, satellite glial cell activation within stellate ganglia
exacerbates neuronal and cardiac remodeling (structural and functional) to promote LV
dysfunction and VT/VF (Aim 1). We will investigate the mechanisms by which cardiac injury
activates SGCs in stellate ganglia after injury (Aim 2). Finally, we will determine whether
targeting glial Gq-GPCR Ca2+ signaling or Cx43-mediated glia-neuron/glial- glial
communication mitigates adverse remodeling and arrhythmogenesis following cardiac injury
(Aim 3). The results of this proposal will 1) indicate whether and how satellite glial cell activation
contributes to sympathetic imbalance after cardiac injury; and 2) determine whether targeting
satellite glial cell activation offers therapeutic potential in chronic cardiac injury.

## Key facts

- **NIH application ID:** 11003946
- **Project number:** 3R01HL162717-03S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Olujimi A Ajijola
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $102,307
- **Award type:** 3
- **Project period:** 2022-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11003946

## Citation

> US National Institutes of Health, RePORTER application 11003946, Understanding Modulation of Neuronal Subpopulations by Sympathetic Glia (3R01HL162717-03S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11003946. Licensed CC0.

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