Department of Experimental and Clinical Medicine, Section of Neuroscience and Cell Biology, Università Politecnica delle Marche, 60026, Ancona, Italy; Center for Neurobiology of Aging, INRCA, IRCCS, Ancona, Italy.
Institute of Human Physiology, Università Cattolica del Sacro Cuore, 00168, Rome, Italy; Fondazione Policlinico Universitario A. Gemelli - IRCCS, 00168, Rome, Italy.
Neuropharmacology. 2019 Dec 15;161:107737. doi: 10.1016/j.neuropharm.2019.107737. Epub 2019 Aug 7.
Cultured rat cortical neurons co-expressing VGLUT1 and VGAT (mixed synapses) co-release Glu and GABA. Here, mixed synapses were studied in cultured mouse cortical neurons to verify whether in mice mixed synapses co-release Glu and GABA, and to gain insight into how they may influence excitation/inhibition balance. Results showed the existence of synapses and autapses that co-release Glu and GABA in cultured mouse cortical neurons, and the ability of both neurotransmitters to evoke postsynaptic responses mediated by ionotropic receptors. We studied the short-term plasticity of glutamatergic, GABAergic, and mixed responses and we found that the kinetics of mixPSC amplitude depression was similar to that observed in EPSCs, but it was different from that of IPSCs. We found similar presynaptic release characteristics in glutamatergic and mixed synapses. Analysis of postsynaptic features, obtained by measuring AMPAR- and NMDAR-mediated currents, showed that AMPAR-mediated currents were significantly higher in pure glutamatergic than in mixed synapses, whereas NMDAR-mediated currents were not significantly different from those measured in mixed synapses. Overall, our findings demonstrate that glutamatergic and mixed synapses share similar electrophysiological properties. However, co-release of GABA and Glu influences postsynaptic ionotropic glutamatergic receptor subtypes, thus selectively influencing AMPAR-mediated currents. These findings strengthen the view that mixed neurons can play a key role in CNS development and in maintaining the excitation-inhibition balance.
共表达 VGLUT1 和 VGAT 的培养大鼠皮质神经元（混合突触）共同释放 Glu 和 GABA。在这里，研究了培养的小鼠皮质神经元中的混合突触，以验证在小鼠中混合突触是否共同释放 Glu 和 GABA，并深入了解它们如何影响兴奋/抑制平衡。结果表明，在培养的小鼠皮质神经元中存在共同释放 Glu 和 GABA 的突触和自突触，并且两种神经递质都能够通过离子型受体介导的突触后反应。我们研究了谷氨酸能、GABA 能和混合反应的短期可塑性，发现混合 PSCC 幅度抑制的动力学与观察到的 EPSC 相似，但与 IPSC 不同。我们发现谷氨酸能和混合突触具有相似的突触前释放特征。通过测量 AMPAR 和 NMDAR 介导的电流来分析突触后特征，结果表明，纯谷氨酸能突触中 AMPAR 介导的电流明显高于混合突触，而 NMDAR 介导的电流与混合突触中测量的电流没有显著差异。总体而言，我们的研究结果表明，谷氨酸能和混合突触具有相似的电生理特性。然而，GABA 和 Glu 的共同释放会影响突触后离子型谷氨酸能受体亚型，从而选择性地影响 AMPAR 介导的电流。这些发现进一步证实了混合神经元在中枢神经系统发育和维持兴奋-抑制平衡中起着关键作用。
