Neuroscience Institute, National Research Council (CNR), 35121, Padova, Italy.
Department of Biomedical Sciences, Università degli Studi di Padova, 35121, Padova, Italy.
Nat Commun. 2018 Jan 8;9(1):82. doi: 10.1038/s41467-017-02642-6.
The signaling diversity of GABAergic interneurons to post-synaptic neurons is crucial to generate the functional heterogeneity that characterizes brain circuits. Whether this diversity applies to other brain cells, such as the glial cells astrocytes, remains unexplored. Using optogenetics and two-photon functional imaging in the adult mouse neocortex, we here reveal that parvalbumin- and somatostatin-expressing interneurons, two key interneuron classes in the brain, differentially signal to astrocytes inducing weak and robust GABA receptor-mediated Ca elevations, respectively. Furthermore, the astrocyte response depresses upon parvalbumin interneuron repetitive stimulations and potentiates upon somatostatin interneuron repetitive stimulations, revealing a distinguished astrocyte plasticity. Remarkably, the potentiated response crucially depends on the neuropeptide somatostatin, released by somatostatin interneurons, which activates somatostatin receptors at astrocytic processes. Our study unveils, in the living brain, a hitherto unidentified signaling specificity between interneuron subtypes and astrocytes opening a new perspective into the role of astrocytes as non-neuronal components of inhibitory circuits.
γ-氨基丁酸能中间神经元向后突触神经元传递信号的多样性对于产生大脑回路的功能异质性至关重要。这种多样性是否适用于其他脑细胞，如神经胶质细胞星形胶质细胞，仍有待探索。本研究在成年小鼠大脑皮层中使用光遗传学和双光子功能成像，揭示了两种关键的脑中间神经元，即表达 Parvalbumin 和 Somatostatin 的中间神经元，分别以弱和强 GABA 受体介导的 Ca 升高的方式向星形胶质细胞传递信号。此外，星形胶质细胞的反应在 Parvalbumin 中间神经元重复刺激下被抑制，而在 Somatostatin 中间神经元重复刺激下被增强，揭示了星形胶质细胞的独特可塑性。值得注意的是，增强的反应关键取决于由 Somatostatin 中间神经元释放的神经肽 Somatostatin，它激活星形胶质细胞突起上的 Somatostatin 受体。本研究在活体大脑中揭示了中间神经元亚型和星形胶质细胞之间以前未被识别的信号特异性，为星形胶质细胞作为抑制性回路的非神经元成分的作用开辟了新的视角。
