调控视网膜谷氨酸能波的突触和突触外因素。

Synaptic and extrasynaptic factors governing glutamatergic retinal waves.

作者信息

Blankenship Aaron G, Ford Kevin J, Johnson Juliette, Seal Rebecca P, Edwards Robert H, Copenhagen David R, Feller Marla B

机构信息

Neurosciences Graduate Program, University of California, San Diego, La Jolla, CA 92093, USA.

出版信息

Neuron. 2009 Apr 30;62(2):230-41. doi: 10.1016/j.neuron.2009.03.015.

In the few days prior to eye-opening in mice, the excitatory drive underlying waves switches from cholinergic to glutamatergic. Here, we describe the unique synaptic and spatiotemporal properties of waves generated by the retina's glutamatergic circuits. First, knockout mice lacking vesicular glutamate transporter type 1 do not have glutamatergic waves, but continue to exhibit cholinergic waves, demonstrating that the two wave-generating circuits are linked. Second, simultaneous outside-out patch and whole-cell recordings reveal that retinal waves are accompanied by transient increases in extrasynaptic glutamate, directly demonstrating the existence of glutamate spillover during waves. Third, the initiation rate and propagation speed of retinal waves, as assayed by calcium imaging, are sensitive to pharmacological manipulations of spillover and inhibition, demonstrating a role for both signaling pathways in shaping the spatiotemporal properties of glutamatergic retinal waves.

在小鼠睁眼的前几天，波所依赖的兴奋性驱动从胆碱能转变为谷氨酸能。在此，我们描述了视网膜谷氨酸能回路产生的波独特的突触和时空特性。首先，缺乏1型囊泡谷氨酸转运体的基因敲除小鼠没有谷氨酸能波，但继续表现出胆碱能波，这表明两个波产生回路是相关联的。其次，同时进行的外向膜片钳和全细胞记录显示，视网膜波伴随着突触外谷氨酸的短暂增加，直接证明了波期间谷氨酸溢出的存在。第三，通过钙成像测定的视网膜波的起始速率和传播速度对溢出和抑制的药理学操作敏感，表明这两种信号通路在塑造谷氨酸能视网膜波的时空特性中都起作用。