ORCID

https://orcid.org/0000-0002-2093-2396

Keywords

nociceptive, CGRP, spinal afferent, stomach, 3D scaffold, sex differences

Abstract

Understanding the sensory nervous system’s precise innervation of visceral organs remains a major challenge in systems neuroscience, particularly for designing neuromodulatory therapies. In this study, we topographically mapped calcitonin gene-related peptide (CGRP, a nociceptive marker) afferent axons in the flat mounts of the whole stomach muscular layers of male and female mice and built a 3D digital rodent stomach scaffold that combines high-resolution structural images and nerve-specific mapping onto a common coordinate framework. Using a pipeline developed within the NIH SPARC (Stimulate Peripheral Activity to Relieve Conditions), we constructed a 3D scaffold of the stomach wall layers, segmented spinal afferent and nociceptive innervation from confocal images and whole mount tissues, and registered nerve data to the scaffold. We found that: 1) CGRP-IR axons entered the stomach and formed an extensive terminal network in the blood vessels, myenteric ganglia, and longitudinal and circular muscles. 2) The CGRP-IR axon innervation density varied depending on the region and gastric target of the stomach. 3) CGRP-IR axons had similar morphologies and distribution patterns in male and female mice. 4) The CGRP-IR nociceptive and spinal afferent innervation maps were annotated with fiducial markers and fitted to a generic 3D stomach scaffold. 5) The scaffold serves as a consistent reference frame to track and analyze the complex interaction between nerve fibers and gastric targets in between layers, enabling population studies and data comparison among samples and across experimental groups. Our methodology contributes to a better understanding of the visceral afferent nervous system, as well as establishing a reproducible computational framework for mapping and manipulating autonomic pathways by stimulating targeted nerves to manage chronic pain and improve organ function, with applications spanning basic neuroanatomy to translational clinical intervention.

Completion Date

2025

Semester

Fall

Committee Chair

Cheng, Zixi Jack

Degree

Doctor of Philosophy (Ph.D.)

College

College of Medicine

Department

Burnett School of Biomedical Sciences

Format

PDF

Release Date

12-15-2027

Document Type

Dissertation

Campus Location

Orlando (Main) Campus

Subjects

Stomach--Innervation; Digestive organs--Innervation; Gastrointestinal system--Innervation; Viscera--Innervation; Neuroanatomy--Research

Available for download on Wednesday, December 15, 2027

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