[Single-nucleus transcriptome of the gracile nucleus reveals multi-modular complex functional genes in excitatory...

The gracile nucleus (GR), conventionally regarded as a primary relay in the ascending somatosensory pathway, plays a pivotal role in processing fine-touch, vibration, and proprioceptive information originating from the lower body. The fidelity of this processing is fundamental to sensory perception and motor coordination. We employed single-nucleus RNA sequencing (snRNA-seq) to establish a high-resolution, comprehensive transcriptomic atlas of the adult mouse GR. We systematically dissected the cellular architecture of the GR. Our analysis delineated all major neuronal and non-neuronal populations, and revealed a rich diversity of excitatory projection neuron subtypes, each characterized by a unique transcriptomic signature and a distinct spatial organization. Functional gene enrichment analysis unveiled a striking dichotomy in the roles of these subtypes. We identified a cohort of "conduction-type" neurons, specialized for the rapid and high-fidelity transmission of core somatosensory information, thereby preserving the integrity of the somatosensory map. In contrast, a second cohort of "modulatory-type" neurons demonstrated enriched expression of a diverse repertoire of neuropeptides, including somatostatin and cholecystokinin. These neurons are positioned to exert state-dependent modulation over the principal sensory pathways, fine-tuning information throughput in response to behavioral context or internal states such as arousal and attention. Notably, our findings reveal that these excitatory neurons do not exist as discrete, static populations. Instead, they are organized along a continuous transcriptional spectrum, which appears to represent a trajectory of sensory learning and adaptation. One pole of this continuum, representing an "adapted" state, exhibited significant enrichment of activity-dependent immediate-early genes integral to synaptic plasticity, learning, and memory, such as Fos, Arc, and Npas4. By elucidating this intricate cellular architecture and intrinsic plasticity, our study provides novel insights into information processing within the somatosensory system and offers a valuable resource for investigating the pathophysiology of related disorders, including chronic pain and sensory neuropathies.