Anatomical modeling of visceral afferent innervation in the rodent stomach.

Understanding the sensory nervous system's precise innervation of visceral organs remains a major challenge in systems neuroscience, particularly for designing neuromodulatory therapies. Here, we introduce a digital twin of the rodent stomach that combines high-resolution structural images and nerve-specific mapping onto a common coordinate scaffold. Using a pipeline developed within the NIH SPARC (Stimulate Peripheral Activity to Relieve Conditions) framework, we used immunohistochemistry (fluorescence and chromogenic) and anterograde tracing to label Calcitonin gene-related peptide (CGRP) axons and tracer-labeled spinal afferents in the whole stomach flat-mounts, digitized the axons, and registered axon data from nerve tracing experiments. These datasets were integrated into a standard scaffold, enabling cross-specimen alignment and annotation. The scaffold promotes integration of topographically anatomical and physiological metadata into the scaffold to enable simulation of neuromodulatory input effects, advances research on targeted nerve stimulation to improve organ function, and supports iterative development of closed-loop bioelectronic devices. The scaffold is publicly available via the SPARC Portal and supports modular extension to other species and organ systems. Our methodology contributes to a better understanding of the visceral afferent nervous system and multi-organ connectome, as well as establishing a reproducible computational framework for mapping and manipulating autonomic pathways in visceral organs, with applications spanning basic neuroanatomy to translational clinical intervention.