Department of Otolaryngology, University of Pittsburgh School of Medicine, Eye and Ear Institute, Pittsburgh, Pennsylvania, USA.
Nat Neurosci. 2010 Feb;13(2):232-8. doi: 10.1038/nn.2478. Epub 2010 Jan 17.
Many nonglutamatergic synaptic terminals in the mammalian brain contain the vesicular glutamate transporter 3 (VGLUT3), indicating that they co-release the excitatory neurotransmitter glutamate. However, the functional role of glutamate co-transmission at these synapses is poorly understood. In the auditory system, VGLUT3 expression and glutamate co-transmission are prominent in a developing GABA/glycinergic sound-localization pathway. We found that mice with a genetic deletion of Vglut3 (also known as Slc17a8) had disrupted glutamate co-transmission and severe impairment in the refinement of this inhibitory pathway. Specifically, loss of glutamate co-transmission disrupted synaptic silencing and the strengthening of GABA/glycinergic connections that normally occur with maturation. Functional mapping studies further revealed that these deficits markedly degraded the precision of tonotopy in this inhibitory auditory pathway. These results indicate that glutamate co-transmission is crucial for the synaptic reorganization and topographic specification of a developing inhibitory circuit.
哺乳动物大脑中的许多非谷氨酸能突触末梢含有囊泡谷氨酸转运体 3（VGLUT3），表明它们共同释放兴奋性神经递质谷氨酸。然而，这些突触中谷氨酸共传递的功能作用还知之甚少。在听觉系统中，VGLUT3 的表达和谷氨酸共传递在 GABA/甘氨酸能声音定位途径的发育中很明显。我们发现，Vglut3（也称为 Slc17a8）基因缺失的小鼠存在谷氨酸共传递中断和这种抑制性途径的精细调节严重受损。具体来说，谷氨酸共传递的缺失破坏了正常成熟过程中出现的突触抑制和 GABA/甘氨酸能连接的增强。功能映射研究进一步表明，这些缺陷显著降低了这个抑制性听觉通路中音调拓扑的精确性。这些结果表明，谷氨酸共传递对于发育中抑制性回路的突触重组和拓扑特化至关重要。
