GABAergic spill-over transmission onto hippocampal mossy fiber boutons
GABAergic spill-over transmission onto hippocampal mossy fiber boutons
复制标题
DOI：
10.1523/jneurosci.4996-06.2007
复制
发表时间：
2007-01-24
影响因子：
5.3
通讯作者：
Geiger, Joerg R. P.
中科院分区：
文献类型：
--
作者：
Alle, Henrik;Geiger, Joerg R. P.
突触前离子型GABA（A）受体被认为参与调节皮层神经元能突触传递。在这里，我们分析了突触前GABAA受体介导的电流（34摄氏度）记录苔藓纤维扣（MFB）在大鼠海马切片。在幼年和成年动物的MFB中，GABA喷吸激活了被GABA（A）受体拮抗剂阻断的电流。0.65mS中心点cm（2）的电导密度与其他突触前终末的电导密度相当。单通道电导率为36 pS（对称氯离子），估计GABAA受体密度为20 - 200个受体/MFB。突触前GABA（A）受体可能含有α（2）-亚单位，如其唑吡坦敏感性所示。根据受体的低表观GABA亲和力（EC 50 = 60 μ M）和GABA转运蛋白对周围GABA浓度的严格控制，未观察到突触前GABA（A）受体的紧张性背景激活。相反，细胞外高频刺激导致短暂的突触前电流，这是由GABAA受体拮抗剂阻断，但增强了GAT1（GABA转运蛋白1）的阻断，表明这些电流产生的GABA溢出和随后的突触前GABAA受体激活。突触前溢出电流被抑制药理大麻素1（CB1）受体激活，这表明GABA主要是由CB1受体表达的中间神经元亚群释放。因为轴突中的GABA（A）受体被认为起去极化作用，所以表达CB1受体的中间神经元的高活性将对突触前膜电位产生实质性影响，从而调节苔藓纤维-CA3突触处的动作电位诱发的递质释放。
Presynaptic ionotropic GABA(A) receptors have been suggested to contribute to the regulation of cortical glutamatergic synaptic transmission. Here, we analyzed presynaptic GABAA receptor-mediated currents (34 degrees C) recorded from mossy fiber boutons (MFBs) in rat hippocampal slices. In MFBs from young and adult animals, GABA puff application activated currents that were blocked by GABA(A) receptor antagonists. The conductance density of 0.65 mS center dot cm(2) was comparable to that of other presynaptic terminals. The single-channel conductance was 36 pS (symmetrical chloride), yielding an estimated GABAA receptor density of 20-200 receptors per MFB. Presynaptic GABA(A) receptors likely contain alpha(2)-subunits as indicated by their zolpidem sensitivity. In accordance with the low apparent GABA affinity (EC50 = 60 mu M) of the receptors and a tight control of ambient GABA concentration by GABA transporters, no tonic background activation of presynaptic GABA(A) receptors was observed. Instead, extracellular high-frequency stimulation led to transient presynaptic currents, which were blocked by GABAA receptor antagonists but were enhanced by block of GAT1 (GABA transporter 1), indicating that these currents were generated by GABA spill-over and subsequent presynaptic GABAA receptor activation. Presynaptic spill-over currents were depressed by pharmacological cannabinoid 1 (CB1) receptor activation, suggesting that GABA was released predominantly by a CB1 receptor-expressing interneuron subpopulation. Because GABA(A) receptors in axons are considered to act depolarizing, high activity of CB1 receptor-expressing interneurons will exert substantial impact on presynaptic membrane potential, thus modulating action potential-evoked transmitter release at the mossy fiber-CA3 synapse.