INSERM, UMR 839, F75005, Paris, France.
J Neurosci. 2012 Aug 22;32(34):11835-40. doi: 10.1523/JNEUROSCI.5543-11.2012.
Dentate gyrus granule cells have been suggested to corelease GABA and glutamate both in juvenile animals and under pathological conditions in adults. Although mossy fiber terminals (MFTs) are known to express glutamic acid decarboxylase (GAD) in early postnatal development, the functional role of GABA synthesis in MFTs remains controversial, and direct evidence for synaptic GABA release from MFTs is missing. Here, using GAD67-GFP transgenic mice, we show that GAD67 is expressed only in a population of immature granule cells in juvenile animals. We demonstrate that GABA can be released from these cells and modulate mossy fiber excitability through activation of GABAB autoreceptors. However, unitary postsynaptic currents generated by individual, GAD67-expressing granule cells are purely glutamatergic in all postsynaptic cell types tested. Thus GAD67 expression does not endow dentate gyrus granule cells with a full GABAergic phenotype and GABA primarily instructs the pre- rather than the postsynaptic element.
齿状回颗粒细胞被认为在幼年动物和成年病理条件下均可共释放 GABA 和谷氨酸。尽管已知苔藓纤维末梢(MFT)在出生后早期发育过程中表达谷氨酸脱羧酶(GAD),但 MFT 中 GABA 合成的功能作用仍存在争议,并且缺乏来自 MFT 的 GABA 释放的直接证据。在这里,我们使用 GAD67-GFP 转基因小鼠,表明 GAD67 仅在幼年动物的一群不成熟的颗粒细胞中表达。我们证明 GABA 可以从这些细胞中释放出来,并通过激活 GABAB 自身受体来调节苔藓纤维兴奋性。然而,通过在所有测试的突触后细胞类型中生成单个 GAD67 表达的颗粒细胞的单位突触后电流,证明它们完全是谷氨酸能的。因此,GAD67 的表达并没有赋予齿状回颗粒细胞完全的 GABA 能表型,并且 GABA 主要指示的是前而不是后突触成分。