Understanding how sensory information from the body reaches and is processed by the brain remains one of the central challenges in neuroscience. This large-scale project aims to map and characterize, at single-cell resolution, the central brainstem circuits responsible for transmitting auditory, vestibular, and somatosensory signals to the brain. These circuits play a fundamental role in our perception of sound, balance, and touch, yet their cellular composition, connectivity, and transcriptional diversity remain incompletely defined. To address this, we will deploy state-of-the-art single-cell and single-nucleus RNA sequencing technologies to profile the neuronal and non-neuronal cell types that constitute the sensory relay centers in the brainstem. In parallel, we will apply viral-based retrograde tracing combined with transcriptomic analysis (Retro-Seq) to establish precise input-output relationships and uncover molecular signatures of projection-defined neuronal populations. Together, these approaches will generate a comprehensive molecular and anatomical map of the sensory brainstem, laying the foundation for understanding how sensory signals are processed and integrated at this level. Beyond this foundational work, the project also addresses critical unmet clinical needs. Sensory disorders such as tinnitus, hyperacusis, and age-related sensory decline affect millions of individuals worldwide, often with no effective treatments. Using cellular and molecular profiling in relevant preclinical models of these conditions, we will investigate how the sensory brainstem circuits are altered in disease and aging. This includes identifying cell-type specific vulnerabilities, changes in gene expression, and circuit remodeling that may underlie pathological sensory perception. This project is computationally intensive, relying on advanced bioinformatics pipelines and machine learning models—including probabilistic and deep variational inference—to analyze high-dimensional single-cell datasets. We will integrate Smart-seq3 transcriptomes, retrograde-labeled cell populations, and spatial transcriptomic data to uncover molecular signatures and cell-state transitions. The scale and complexity of these analyses require significant computing power, memory, and storage resources to resolve fine-grained cellular diversity, lineage relationships, and the anatomical logic of brainstem circuits. This dual focus—on basic mapping and disease-related changes—provides both deep mechanistic insight and potential avenues for therapeutic development. The project is enabled by and will further develop advanced data storage and computing capacities to handle and integrate large-scale single-cell datasets, connectomics data, and spatial transcriptomic information. By revealing the molecular logic and circuit architecture of sensory brainstem pathways, and their alteration in disease, this project will establish a new framework for understanding and eventually treating sensory disorders rooted in central neural circuits.