大鼠小脑苔藓纤维-颗粒细胞突触在长时程增强过程中神经递质释放增加。
Increased neurotransmitter release during long-term potentiation at mossy fibre-granule cell synapses in rat cerebellum.
作者信息
Sola Elisabetta, Prestori Francesca, Rossi Paola, Taglietti Vanni, D'Angelo Egidio
机构信息
Department of Physiology and Pharmacological Sciences, University of Pavia, Via Forlanini 6, 27100 Pavia, I-27100, Italy.
出版信息
J Physiol. 2004 Jun 15;557(Pt 3):843-61. doi: 10.1113/jphysiol.2003.060285. Epub 2004 Apr 16.
During long-term potentiation (LTP) at mossy fibre-granule cell synapses in rat cerebellum synaptic transmission and granule cell intrinsic excitability are enhanced. Although it is clear that changes in granule cell excitability are mediated postsynaptically, there is as yet no direct evidence for the site and mechanism of changes in transmission. To approach this problem, evoked postsynaptic currents (EPSCs) and miniature synaptic currents (mEPSCs) were recorded by patch-clamp in cerebellar slices obtained from P17-P23 rats. LTP was induced by theta-burst stimulation paired with depolarization. During LTP, the EPSCs showed a significant decrease in the coefficient of variation (CV; 28.9 +/- 5.2%, n= 8; P < 0.002), the number of failures (87.1 +/- 41.9%, n= 8; P < 0.04), and the paired-pulse ratio (PPR; 25.5 +/- 4.1% n= 5; P < 0.02). Similar changes were observed by increasing neurotransmitter release (extracellular solutions with high Ca(2+)/Mg(2+) ratio), whereas increases in CV, numbers of failures and PPR occurred when release was decreased (extracellular solutions with low Ca(2+)/Mg(2+) ratio; 10 microm Cl-adenosine). No changes followed modifications of postsynaptic holding potentials, while CV and failures were reduced when the number of active synapses was increased. LTP was prevented by use of solutions with high Ca(2+)/Mg(2+) ratio. Moreover, LTP and the associated CV decrease were observed in the spillover-mediated component of AMPA EPSCs and in NMDA EPSCs. During LTP, mEPSCs did not change in amplitude or variability but significantly increased in frequency (47.6 +/- 16%, n= 4; P < 0.03). By binomial analysis changes in EPSCs were shown to be due to increased release probability (from 0.6 +/- 0.08 to 0.73 +/- 0.06, n= 7; P < 0.02) with a constant number of three to four releasing sites. These observations provide evidence for increased neurotransmitter release during LTP at mossy fibre-granule cell synapses.
在大鼠小脑苔藓纤维-颗粒细胞突触的长时程增强（LTP）过程中，突触传递和颗粒细胞内在兴奋性增强。虽然很明显颗粒细胞兴奋性的变化是由突触后介导的，但对于传递变化的位点和机制尚无直接证据。为了解决这个问题，在从P17 - P23大鼠获取的小脑切片中，通过膜片钳记录诱发的突触后电流（EPSCs）和微小突触电流（mEPSCs）。通过与去极化配对的theta波串刺激诱导LTP。在LTP期间，EPSCs的变异系数（CV；28.9±5.2%，n = 8；P < 0.002）、失败次数（87.1±41.9%，n = 8；P < 0.04）和双脉冲比率（PPR；25.5±4.1%，n = 5；P < 0.02）均显著降低。通过增加神经递质释放（高Ca(2 +)/Mg(2 +)比率的细胞外溶液）观察到类似变化，而当释放减少时（低Ca(2 +)/Mg(2 +)比率的细胞外溶液；10 μM Cl - 腺苷），CV、失败次数和PPR增加。突触后钳制电位改变后无变化，而当活跃突触数量增加时，CV和失败次数减少。使用高Ca(2 +)/Mg(2 +)比率的溶液可阻止LTP。此外，在AMPA EPSCs的溢出介导成分和NMDA EPSCs中观察到LTP及相关的CV降低。在LTP期间，mEPSCs的幅度或变异性没有变化，但频率显著增加（47.6±16%，n = 4；P < 0.03）。通过二项式分析表明EPSCs的变化是由于释放概率增加（从0.6±0.08增加到0.73±0.06，n = 7；P < 0.02），释放位点数量恒定为三到四个。这些观察结果为苔藓纤维-颗粒细胞突触LTP期间神经递质释放增加提供了证据。
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