Hierarchically and Temporally Distinct Ca2+ Signaling Across Thalamic Nuclei During Nociceptive Stimulation

Abstract

ABSTRACT Background The thalamus serves as a critical relay hub for transmitting peripheral nociceptive information to the cerebral cortex and plays a central role in the sensory, motor, affective, and cognitive dimensions of pain processing. However, the dynamic response patterns of distinct thalamic nuclei during stimulus‐pain processing remain poorly understood. Methods In this study, fiber photometry was employed to record calcium (Ca2+) signals from multiple thalamic nuclei under two intensities of nociceptive somatic stimulation. Results The results showed that all recorded nuclei exhibited rapid increases in Ca2+ signals following nociceptive stimulation; however, the evoked Ca2+ signals differed markedly in peak amplitudes and peak times across nuclei. Cluster analysis further revealed a clear spatial stratification of thalamic responses to nociceptive stimulation, with medially located nuclei generally exhibiting stronger Ca2+ responses than laterally located nuclei. In addition, thalamic nuclei differed in their sensitivity to stimulus intensity, with some showing pronounced intensity‐dependent Ca2+ responses, whereas others exhibited minimal changes. Notably, within the dorsal thalamus, the parafascicular nucleus (PF) exhibited the shortest Ca2+ signal peak time, whereas the posterior nucleus (PO) showed the longest. Morphological analyses further revealed distinct downstream projection targets and cortical axonal distribution patterns between PF and PO. Conclusions This study reveals a thalamus‐wide functional stratification of neuronal Ca2+ dynamics during nociceptive processing, with distinct thalamic nuclei exhibiting specialized temporal profiles and intensity‐encoding properties. Collectively, these findings provide new experimental evidence supporting the view that the thalamus acts as a distributed and hierarchical hub for pain information processing.