Safiulina Victoria F, Fattorini Giorgia, Conti Fiorenzo, Cherubini Enrico
Neuroscience Programme, International School for Advanced Studies, 34014 Trieste, Italy.
J Neurosci. 2006 Jan 11;26(2):597-608. doi: 10.1523/JNEUROSCI.4493-05.2006.
In the adult rat hippocampus, granule cell mossy fibers (MFs) form excitatory glutamatergic synapses with CA3 principal cells and local inhibitory interneurons. However, evidence has been provided that, in young animals and after seizures, the same fibers can release in addition to glutamate GABA. Here we show that, during the first postnatal week, stimulation of granule cells in the dentate gyrus gave rise to monosynaptic GABAA-mediated responses in principal cells and in interneurons. These synapses were indeed made by MFs because they exhibited strong paired-pulse facilitation, high sensitivity to the metabotropic glutamate receptor agonist l-AP-4, and short-term frequency-dependent facilitation. MF responses were potentiated by blocking the plasma membrane GABA transporter GAT-1 with NO-711 or by allosterically modulating GABAA receptors with flurazepam. Chemical stimulation of granule cell dendrites with glutamate induced barrages of GABAA-mediated postsynaptic currents into target neurons. Furthermore, immunocytochemical experiments demonstrated colocalization of vesicular GABA transporter with vesicular glutamate transporter-1 and zinc transporter 3, suggesting that GABA can be taken up and stored in synaptic vesicles of MF terminals. Additional fibers releasing both glutamate and GABA into principal cells and interneurons were recruited by increasing the strength of stimulation. Both the GABAergic and the glutamatergic component of synaptic currents occurred with the same latency and were reversibly abolished by l-AP-4, indicating that they originated from the MFs. GABAergic signaling may play a crucial role in tuning hippocampal network during postnatal development. Low-threshold GABA-releasing fibers may undergo elimination, and this may occur when GABA shifts from the depolarizing to the hyperpolarizing direction.
在成年大鼠海马体中，颗粒细胞苔藓纤维（MFs）与CA3主细胞和局部抑制性中间神经元形成兴奋性谷氨酸能突触。然而，已有证据表明，在幼小动物和癫痫发作后，相同的纤维除了释放谷氨酸外还能释放γ-氨基丁酸（GABA）。在这里，我们表明，在出生后的第一周，刺激齿状回中的颗粒细胞会在主细胞和中间神经元中引发单突触GABAA介导的反应。这些突触确实是由MFs形成的，因为它们表现出强烈的双脉冲易化、对代谢型谷氨酸受体激动剂l-AP-4高度敏感以及短期频率依赖性易化。通过用NO-711阻断质膜GABA转运体GAT-1或用氟西泮变构调节GABAA受体，MF反应得到增强。用谷氨酸对颗粒细胞树突进行化学刺激会在靶神经元中引发GABAA介导的突触后电流爆发。此外，免疫细胞化学实验表明囊泡GABA转运体与囊泡谷氨酸转运体-1和锌转运体3共定位，这表明GABA可以被摄取并储存在MF终末的突触小泡中。通过增加刺激强度可募集更多向主细胞和中间神经元释放谷氨酸和GABA的纤维。突触电流的GABA能成分和谷氨酸能成分具有相同的潜伏期，并且都被l-AP-4可逆地消除，这表明它们都起源于MFs。GABA能信号传导可能在出生后发育过程中对海马网络的调节中起关键作用。低阈值释放GABA的纤维可能会经历消除过程，这可能发生在GABA从去极化方向转变为超极化方向时。
