The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University, Baltimore, MD 21205, USA.
Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Göttingen 37075, Germany.
Neuron. 2021 Aug 18;109(16):2545-2555.e7. doi: 10.1016/j.neuron.2021.06.010. Epub 2021 Jul 9.
Astrocytes play an essential role in the development of neural circuits by positioning transporters and receptors near synapses and secreting factors that promote synaptic maturation. However, the mechanisms that coordinate astrocyte and neural maturation remain poorly understood. Using in vivo imaging in unanesthetized neonatal mice, we show that bursts of neuronal activity passing through nascent sound processing networks reliably induce calcium transients in astrocytes. Astrocyte transients were dependent on intense neuronal activity and constrained to regions near active synapses, ensuring close spatial and temporal coordination of neuron and astrocyte activity. Astrocyte responses were restricted to the pre-hearing period and induced by synergistic activation of two metabotropic glutamate receptors, mGluR5 and mGluR3, which promoted IP3R2-dependent calcium release from intracellular stores. The widespread expression of these receptors by astrocytes during development and the prominence of neuronal burst firing in emerging neural networks may help coordinate the maturation of excitatory synapses.
星形胶质细胞在神经回路的发育中起着至关重要的作用，它们将转运体和受体定位在突触附近，并分泌促进突触成熟的因子。然而，协调星形胶质细胞和神经成熟的机制仍知之甚少。我们利用未麻醉的新生小鼠体内成像技术，发现通过新生声音处理网络传递的神经元活动爆发能够可靠地诱导星形胶质细胞中的钙瞬变。星形胶质细胞的瞬变依赖于强烈的神经元活动，并局限于活性突触附近的区域，从而确保神经元和星形胶质细胞活动的紧密空间和时间协调。星形胶质细胞的反应仅限于听觉前时期，并且由两种代谢型谷氨酸受体 mGluR5 和 mGluR3 的协同激活诱导，这促进了细胞内储存的 IP3R2 依赖性钙释放。这些受体在发育过程中广泛表达于星形胶质细胞中，而神经元爆发式放电在新兴神经网络中的出现可能有助于协调兴奋性突触的成熟。
