群馬大学大学院医学系研究科機能形態学・助教一ノ瀬 聡太郎Sotaro IchinoseDepartment of Anatomy, Gunma University Graduate School of MedicineAbstractMaintaining a proper balance between neuronal excitation and inhibition (E/I balance) is essential for stable circuit function and behavioral flexibility. In this study, we identified a novel mechanism by which the transmembrane adhesion molecule Teneurin-2 (TEN2) promotes inhibitory synapse formation. TEN2 directly binds to the microtubule plus-end tracking protein EB, and this interaction is regulated by calcium-dependent liquid-liquid phase separation (LLPS) involving TEN2’s intrinsically disordered intracellular domain. In cultured neurons, activity-induced Ca²+ influx promoted TEN2–EB interaction, enhanced microtubule recruitment, and increased gephyrin clustering, suggesting that TEN2 contributes to activity-dependent inhibitory synapse stabilization.To facilitate future in vivo studies, we developed a multiscale analysis pipeline to assess E/I balance in the anterior cingulate cortex. This platform integrates depth-resolved synaptic mapping, geometric-logarithmic transformation, and behavioral profiling. In a prenatal valproic acid (VPA) exposure model, the pipeline successfully revealed laminar-specific synaptic disruptions and impaired social behavior. Notably, voluntary exercise partially reversed these phenotypes, validating the system’s sensitivity to intervention effects.Although in vivo manipulation of TEN2–microtubule interactions remains a future goal, our findings provide molecular insight into this regulatory mechanism and establish a robust framework for evaluating circuit-level and behavioral outcomes in neurodevelopmental disorder models.はじめに神経回路が安定した情報処理を行い，多様な行動要求に柔軟に応答するためには，興奮性シナプスと抑制性シナプスの機能的均衡，すなわち興奮 – 抑制バランス（E/I バランス）の維持が不可欠である．― 97 ―微小管－ TEN2 複合体相互作用による E/I バランス制御の追究Microtubule–TEN2 complexes as regulators of cortical E/I balance
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