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

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.