Superficial spinal Tac1-lineage neurons are polymodal nociceptive

Abstract

Tac1-lineage neurons in the spinal dorsal horn have been implicated in coping behavior in response to sustained noxious stimuli, but their developmental origin, cellular heterogeneity, and functional contribution remain incompletely understood. Here, we characterized the molecular identity, developmental trajectory, electrophysiological properties, and sensory responses of spinal Tac1-lineage neurons. In adults, Tac1-lineage neurons comprised a heterogeneous population of excitatory and inhibitory interneurons and excitatory projection neurons distributed across the superficial dorsal horn. In contrast, at embryonic day 16.5, Tac1-lineage neurons in laminae I/IIo were exclusively projection neurons, revealing a marked developmental transition in the composition of the Tac1 lineage. Electrophysiological recordings from spinal cord slices further demonstrated substantial functional heterogeneity, with most Tac1-lineage neurons exhibiting phasic or single-spike firing and smaller populations displaying tonic or reluctant firing. In vivo calcium imaging in anesthetized mice revealed prominent responses to noxious mechanical and thermal stimulation. Interestingly, Tac1-lineage neurons used distinct strategies to encode cold and heat intensity. Together, these findings reveal pronounced developmental and functional heterogeneity within the Tac1 lineage and demonstrate that adult Tac1-lineage neurons are predominately polymodal nociceptive.