Chamberland Simon, Evstratova Alesya, Tóth Katalin
Quebec Mental Health Institute, Department of Psychiatry and Neuroscience, Laval University, Quebec City, Quebec, Canada, G1J 2G3.
Quebec Mental Health Institute, Department of Psychiatry and Neuroscience, Laval University, Quebec City, Quebec, Canada, G1J 2G3
J Neurosci. 2014 Aug 13;34(33):11032-47. doi: 10.1523/JNEUROSCI.0847-14.2014.
Synaptic short-term plasticity is a key regulator of neuronal communication and is controlled via various mechanisms. A well established property of mossy fiber to CA3 pyramidal cell synapses is the extensive short-term facilitation during high-frequency bursts. We investigated the mechanisms governing facilitation using a combination of whole-cell electrophysiological recordings, electrical minimal stimulation, and random-access two-photon microscopy in acute mouse hippocampal slices. Two distinct presynaptic mechanisms were involved in short-term facilitation, with their relative contribution dependent on extracellular calcium concentration. The synchronization of multivesicular release was observed during trains of facilitating EPSCs recorded in 1.2 mM external Ca(2+) ([Ca(2+)]e). Indeed, covariance analysis revealed a gradual augmentation in quantal size during trains of EPSCs, and application of the low-affinity glutamate receptor antagonist γ-D-glutamylglycine showed an increase in cleft glutamate concentration during paired-pulse stimulation. Whereas synchronization of multivesicular release contributed to the facilitation in 1.2 mM [Ca(2+)]e, variance-mean analysis showed that recruitment of more release sites (N) was likely to account for the larger facilitation observed in 2.5 mM [Ca(2+)]e. Furthermore, this increase in N could be promoted by calcium microdomains of heterogeneous amplitudes observed in single mossy fiber boutons. Our findings suggest that the combination of multivesicular release and the recruitment of additional release sites act together to increase glutamate release during burst activity. This is supported by the compartmentalized spatial profile of calcium elevations in boutons and helps to expand the dynamic range of mossy fibers information transfer.
突触短期可塑性是神经元通讯的关键调节因子，并通过多种机制进行调控。苔藓纤维至CA3锥体细胞突触的一个公认特性是在高频爆发期间广泛的短期易化。我们结合全细胞膜片钳电生理记录、电最小刺激和随机访问双光子显微镜技术，在急性小鼠海马切片中研究了易化的调控机制。短期易化涉及两种不同的突触前机制，它们的相对贡献取决于细胞外钙浓度。在1.2 mM细胞外钙（[Ca(2+)]e）中记录的易化性兴奋性突触后电流（EPSC）串期间，观察到多泡释放的同步性。实际上，协方差分析显示在EPSC串期间量子大小逐渐增加，并且应用低亲和力谷氨酸受体拮抗剂γ-D-谷氨酰甘氨酸显示在配对脉冲刺激期间突触间隙谷氨酸浓度增加。虽然多泡释放的同步性在1.2 mM [Ca(2+)]e中促成了易化，但方差-均值分析表明，在2.5 mM [Ca(2+)]e中观察到的更大易化可能是由于更多释放位点（N）的募集。此外，单个苔藓纤维终扣中观察到的异质幅度的钙微区可促进N的增加。我们的研究结果表明，多泡释放和额外释放位点的募集共同作用，在爆发活动期间增加谷氨酸释放。这得到了终扣中钙升高的分区空间分布的支持，并有助于扩大苔藓纤维信息传递的动态范围。
