biostudies-literatureLiu XYthe Fund of the Ministry of Science and Technology of ChinaExcellent Young Teachers Basic Research Support Program of Heilongjiang Provincialthe Fundamental Research Funds for the Provincial UniversitiesCore Teacher Program of Harbin Medical University15654-15668https://www.ebi.ac.uk/biostudies/studies/S-EPMC12559076biostudies-literatureUnknown62(12)Dose-dependent neuromodulation has been well established; however, the molecular mechanisms underlying astrocytic involvement in this process remain largely unexplored. Using the autoregulation of supraoptic oxytocin (OT) neurons (OTNs) as a model, we investigated the role of distinct astrocytic G proteins and their targets in the dose-dependent effects of OT on OTN activity. The results showed that OT in a low concentration (10 pmol/L, L-OT) excited OTN activity, whereas a high concentration (1 nmol/L, H-OT) inhibited it in brain slices. These effects were abolished upon disruption of astrocytic plasticity using L-aminoadipic acid, a gliotoxin. In primary astrocyte cultures, L-OT slightly reduced the current through astrocyte-specific inwardly rectifying K⁺ channel 4.1 (Kir4.1) while H-OTMolecular neurobiologyG Proteins-Associated Dose-Dependent Effects of Oxytocin on Oxytocin Neuronal Activity and Astrocytic Plasticity of the Supraoptic Nucleus.PMC12559076G2021011014LJJ2023LH1248XYL, 2023YQJH2023031Jiang YLiu YLing SLi YLiu XYJia SQiu DWang XHou CWang YFfalseG Proteins-Associated Dose-Dependent Effects of Oxytocin on Oxytocin Neuronal Activity and Astrocytic Plasticity of the Supraoptic Nucleus.Dose-dependent neuromodulation has been well established; however, the molecular mechanisms underlying astrocytic involvement in this process remain largely unexplored. Using the autoregulation of supraoptic oxytocin (OT) neurons (OTNs) as a model, we investigated the role of distinct astrocytic G proteins and their targets in the dose-dependent effects of OT on OTN activity. The results showed that OT in a low concentration (10 pmol/L, L-OT) excited OTN activity, whereas a high concentration (1 nmol/L, H-OT) inhibited it in brain slices. These effects were abolished upon disruption of astrocytic plasticity using L-aminoadipic acid, a gliotoxin. In primary astrocyte cultures, L-OT slightly reduced the current through astrocyte-specific inwardly rectifying K⁺ channel 4.1 (Kir4.1) while H-OT2025-01-01T00:00:00Z2025 Dec2026-06-05T10:36:19.135Z2026-05-16T03:07:47.224ZS-EPMC125590764069428310.1007/s12035-025-05193-w