Donato R, Nistri A
Biophysics Sector and Istituto Nazionale di Fisica della Materia Unit, International School for Advanced Studies (SISSA), 34014 Trieste, Italy.
J Neurophysiol. 2000 Dec;84(6):2715-24. doi: 10.1152/jn.2000.84.6.2715.
The relative contribution by GABA and glycine to synaptic transmission of motoneurons was investigated using an hypoglossus nucleus slice preparation from neonatal rats. Spontaneous, miniature, or electrically evoked postsynaptic currents (sPSCs, mPSCs, ePSCs, respectively) mediated by glycine or GABA were recorded under whole cell voltage clamp after blocking excitatory glutamatergic transmission with kynurenic acid. The overall majority of Cl(-)-mediated sPSCs was glycinergic, while only one-third was GABAergic; 70 +/- 10% of mPSCs were glycinergic while 22 +/- 8% were GABAergic. Tetrodotoxin (TTX) application dramatically reduced the frequency (and slightly the amplitude) of GABAergic events without changing frequency or amplitude of glycinergic sPSCs. These results indicate that, unlike spontaneous GABAergic transmission, glycine-mediated neurotransmission was essentially independent of network activity. There was a consistent difference in the kinetics of GABAergic and glycinergic responses as GABAergic events had significantly slower rise and decay times than glycinergic ones. Such a difference was always present whenever sPSCs, mPSCs, or ePSCs were measured. Finally, GABAergic and glycinergic mPSCs were differentially modulated by activation of glutamate metabotropic receptors (mGluRs), which are abundant in the hypoglossus nucleus. In fact, the broad-spectrum mGluR agonist (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (50 microM), which in control solution increased the frequency of both GABAergic and glycinergic sPSCs, enhanced the frequency of glycinergic mPSCs only. These results indicate that on brain stem motoneurons, Cl(-)-mediated synaptic transmission is mainly due to glycine rather than GABA and that GABAergic and glycinergic events differ in terms of kinetics and pharmacological sensitivity to mGluR activation or TTX.
利用新生大鼠的舌下神经核切片标本，研究了γ-氨基丁酸（GABA）和甘氨酸对运动神经元突触传递的相对贡献。在用犬尿氨酸阻断兴奋性谷氨酸能传递后，在全细胞电压钳制下记录由甘氨酸或GABA介导的自发性、微小或电诱发的突触后电流（分别为sPSC、mPSC、ePSC）。总体上，大多数Cl⁻介导的sPSC是甘氨酸能的，而只有三分之一是GABA能的；70±10%的mPSC是甘氨酸能的，而22±8%是GABA能的。应用河豚毒素（TTX）可显著降低GABA能事件的频率（并轻微降低其幅度），而不改变甘氨酸能sPSC的频率或幅度。这些结果表明，与自发性GABA能传递不同，甘氨酸介导的神经传递基本上不依赖于网络活动。GABA能和甘氨酸能反应的动力学存在一致差异，因为GABA能事件的上升和衰减时间明显比甘氨酸能事件慢。无论测量sPSC、mPSC还是ePSC，这种差异总是存在。最后，GABA能和甘氨酸能mPSC受到舌下神经核中丰富的谷氨酸代谢型受体（mGluR）激活的不同调节。事实上，广谱mGluR激动剂（±）-1-氨基环戊烷-反式-1,3-二羧酸（50μM）在对照溶液中增加了GABA能和甘氨酸能sPSC的频率，但仅增强了甘氨酸能mPSC的频率。这些结果表明，在脑干运动神经元上，Cl⁻介导的突触传递主要是由于甘氨酸而非GABA，并且GABA能和甘氨酸能事件在动力学以及对mGluR激活或TTX的药理学敏感性方面存在差异。
