# The First Step toward a Neuronal Pacemaker of the Heart

> **NIH NIH F32** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $80,358

## Abstract

Project Summary/Abstract
Neuromodulatory therapies for cardiovascular diseases show great therapeutic potential. However, progress is
hampered by limited in-depth knowledge of cardiac neuroanatomy. This proposal sets forth an innovative
approach to characterizing the pathways at the level of the heart, focusing on the sinoatrial node (SAN). The
SAN region is the site of the native, biologic pacemaker of the heart, and dysfunction of the SAN is common,
particularly in the aging population. The SAN region initiates each heartbeat with robust regularity. SAN
dysfunction can affect quality of life with symptoms syncope and fatigue due to chronotropic incompetence. The
estimated annual incidence of SAN dysfunction in the United States is high, and the only treatment for this
condition is the implantation of a pacemaker. However, pacemaker implantation is still associated with morbidity
such as infection and thrombosis, mainly due to the need for lead implantation within the venous system.
Leadless pacemakers have recently been developed but are still fraught with high peri-procedural complications.
 The autonomic nervous system plays a critical role in many facets of cardiac physiology. In recent years,
increasing attention has been paid to the role of autonomic dysfunction in cardiac pathophysiology in general
and arrhythmogenesis in particular. The development of therapeutics that target the cardiac autonomic nervous
system could provide an effective strategy for treating arrhythmias including SAN dysfunction. Interventions of
cardiac ganglia organized in ganglionated plexi (GPs) at the level of the heart have had mixed results, but
improved characterization of the neuronal subpopulations may ultimately allow for less invasive therapeutics with
reduced side effects.
 In this study, we propose to molecularly phenotype neurons in the right atrial ganglionated plexus using
transcriptomic analysis. Neurons supplying the SAN will be labelled, isolated using laser capture microdissection
(LCM), and analyzed using single-cell RNA sequencing to provide an unbiased approach to identifying neuronal
subpopulations in the RAGP that could be potential therapeutic targets. We will also pursue an optogenetic
approach to modulate intrinsic cardiac neural control of the sinoatrial node. As less invasive strategies for cardiac
pacing are pursued, we propose an optogenetic approach to stimulate SAN-projecting neurons to affect SAN
function. We will investigate this by using a viral vector strategy to transduce SAN-projecting RAGP neurons with
an opsin that will subsequently be photostimulated to exert control of the SAN.

## Key facts

- **NIH application ID:** 9993095
- **Project number:** 1F32HL152609-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Peter Hanna
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $80,358
- **Award type:** 1
- **Project period:** 2020-07-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9993095

## Citation

> US National Institutes of Health, RePORTER application 9993095, The First Step toward a Neuronal Pacemaker of the Heart (1F32HL152609-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9993095. Licensed CC0.

---

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