Vo Thanh Tan, Jung Won Beom, Jin Tong, Im Geun Ho, Lee Soohyun, Kim Seong-Gi
Center for Neuroscience Imaging Research (CNIR), Institute for Basic Science (IBS), Suwon, Republic of Korea.
Department of Biomedical Engineering, Sungkyunkwan University, Suwon, Republic of Korea.
Nat Commun. 2025 Jul 18;16(1):6606. doi: 10.1038/s41467-025-61771-5.
Somatostatin-expressing (SST) interneurons modulate hemodynamic responses both directly and indirectly, but their precise role remains unclear. Here, we investigated the influence of SST interneurons on hemodynamic control in response to optogenetic stimulation of SST neurons and somatosensory stimulation in both awake and anesthetized mice. Prolonged optogenetic stimulation of SST neurons induces fast vasodilation through nitric oxide synthase-expressing neurons that co-express SST, and slow vasodilation mediated by astrocytes. Similar neurovascular coupling mechanisms are observed during prolonged sensory stimulation, which also induces both fast and delayed vasodilation. The delayed vasodilation, mediated by the SST neuron-astrocyte pathway, enhances the specificity of cerebral blood volume (CBV)-weighted fMRI signals to cortical layer 4, as confirmed by chemogenetic inhibition of SST neurons. Our findings indicate that the SST neuron-astrocyte-vascular pathway shapes hemodynamic responses to prolonged stimulation and is critical for achieving high-specificity, laminar-resolution fMRI, which is increasingly pursued in human cognitive studies.
表达生长抑素（SST）的中间神经元直接或间接地调节血流动力学反应，但其确切作用仍不清楚。在这里，我们研究了SST中间神经元对清醒和麻醉小鼠中SST神经元的光遗传学刺激和体感刺激所引起的血流动力学控制的影响。对SST神经元的长时间光遗传学刺激通过共表达SST的一氧化氮合酶表达神经元诱导快速血管舒张，并通过星形胶质细胞介导缓慢血管舒张。在长时间的感觉刺激过程中观察到类似的神经血管耦合机制，这也会诱导快速和延迟的血管舒张。由SST神经元-星形胶质细胞途径介导的延迟血管舒张增强了脑血容量（CBV）加权功能磁共振成像信号对皮质第4层的特异性，这通过对SST神经元的化学遗传学抑制得到证实。我们的研究结果表明，SST神经元-星形胶质细胞-血管途径塑造了对长时间刺激的血流动力学反应，并且对于实现高特异性、层分辨率功能磁共振成像至关重要，而这在人类认知研究中越来越受到关注。
