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Astrocytic α7-nicotinic acetylcholine receptors mediate pain information processing and perception

Year: 2025

Type: article

Abstract: The astrocyte–neuron network in the primary somatosensory cortex (S1) responds dynamically to pain stimuli and plays a pivotal role in pain processing. These stimuli activate astrocytic α7-nicotinic acetylcholine receptors (α7-nAChRs), yet their contribution to pain perception remains largely unclear. This study investigates the role of astrocytic α7-nAChRs in pain information processing and perception. Astrocytic α7-nAChRs were selectively deleted by injecting rAAV5-GfaABC 1 D-NLS-Cre-P2A-mCherry into the S1 region of LoxP-Chrna7 transgenic mice or by tamoxifen administration in ALDH1-CreERT2:Chrna7 loxP/loxP mice. Immunohistochemistry was used to assess the expression of α7-nAChR and gliotransmitter d -serine. Astrocytic Ca 2+ transients were monitored in vivo using two-photon Ca 2+ imaging following AAV5-GfaABC 1 D-cytoGCaMP6f-SV40 labeling. Neuronal Ca 2+ transients in S1 evoked by plantar electric shock were recorded via fiber photometry in freely moving mice. Nociceptive and sensory behaviors were evaluated using hot plate and von Frey tests. Statistical analyses included Welch's t -tests for normally distributed data, Mann–Whitney U tests for non-normal data, and two-way ANOVA. Results showed that conditional deletion of α7-nAChRs in astrocytes markedly reduced d -serine levels within astrocytic territories. Two-photon Ca 2+ imaging and fiber photometry revealed that α7-nAChR deletion attenuated both astrocytic Ca 2+ transients and footshock-evoked neuronal Ca 2+ activity in S1. Behaviorally, thermal pain responses were significantly impaired, whereas tactile thresholds and open-field behaviors were unaffected. These findings identify astrocytic α7-nAChRs in S1 facilitate d -serine levels and enhance astrocytic activity. Their physiological function is essential for pain-related information processing within astrocyte–neuron networks and plays a critical role in regulating pain perception. • Astrocytic α7-nAChRs mediate the interaction of astrocytes and neurons in the S1. • Astrocytic α7-nAChRs in the S1 contribute to pain information processing. • Astrocytic α7-nAChRs in the S1 are required for pain perception.

Source: Neurobiology of Disease

DOI: 10.1016/j.nbd.2025.107245