Kotak V C, Sanes D H
Center for Neural Science, New York University, New York 10003, USA.
Eur J Neurosci. 1997 Nov;9(11):2340-7. doi: 10.1111/j.1460-9568.1997.tb01651.x.
Decreased excitatory synaptic activity during development often leads to pre- and postsynaptic atrophy, as assessed anatomically. The present study considers the effect of decreased excitatory transmission on the maturation of synaptic strength. Towards this end, cochlear nucleus neurons, which project to the ipsilateral lateral superior olive (LSO), were denervated in gerbils at postnatal day 7, before the onset of hearing. This manipulation was intended to disrupt spontaneous glutamatergic transmission in the LSO while sparing the glycinergic afferents from the medial nucleus of the trapezoid body (MNTB). Afferent-evoked synaptic activity was assessed 1-6 days after ablation in a brain slice preparation using whole-cell current- and voltage-clamp recordings. In control animals, ipsilaterally evoked excitatory postsynaptic potentials (EPSPs) were present in 91% of neurons tested, but were observed in only 60% of neurons following cochlea removal. The maximum EPSP amplitude was significantly smaller in manipulated neurons compared with controls, and this was accompanied by a higher incidence of ipsilaterally evoked inhibitory postsynaptic potentials (IPSPs). To study the efficacy of excitatory synapses in greater detail, voltage-clamp recordings were made in the presence of strychnine and AP-5 [D(O)-2-amino-5-phosphonopentanoic acid]. The minimum excitatory postsynaptic current (EPSC) amplitude, presumed to reflect the efficacy of a single glutamatergic afferent, was approximately 40% smaller in manipulated neurons. In contrast, MNTB-evoked IPSPs were similar in neurons from control and ablated animals. However, manipulated neurons often exhibited a rebound depolarization after a hyperpolarizing current pulse or an afferent-evoked IPSP. In 70% of manipulated neurons, synaptically evoked rebound depolarizations were reduced, but not eliminated, by glutamate receptor antagonists. The glycine receptor antagonist strychnine did eliminate the IPSP-associated depolarization in these neurons. Collectively, these results suggest that functional denervation of excitatory afferents decreases their synaptic efficacy as result of both cell loss as well as decreased strength of individual surviving synapses.
从解剖学角度评估，发育过程中兴奋性突触活动的降低通常会导致突触前和突触后萎缩。本研究探讨了兴奋性传递减少对突触强度成熟的影响。为此，在出生后第7天（听力开始之前）对沙鼠投射至同侧外侧上橄榄核（LSO）的耳蜗核神经元进行去神经支配。此操作旨在破坏LSO中的自发性谷氨酸能传递，同时保留来自斜方体内侧核（MNTB）的甘氨酸能传入纤维。在切除神经1 - 6天后，使用全细胞电流钳和电压钳记录，在脑片标本中评估传入诱发的突触活动。在对照动物中，91%的测试神经元存在同侧诱发的兴奋性突触后电位（EPSP），但在去除耳蜗后的神经元中，只有60%观察到该电位。与对照组相比，去神经支配的神经元中最大EPSP幅度显著更小，并且同侧诱发的抑制性突触后电位（IPSP）的发生率更高。为了更详细地研究兴奋性突触的效能，在存在士的宁和AP - 5 [D（O）- 2 - 氨基 - 5 - 膦酰戊酸]的情况下进行电压钳记录。推测反映单个谷氨酸能传入纤维效能的最小兴奋性突触后电流（EPSC）幅度，在去神经支配的神经元中约小40%。相比之下，MNTB诱发的IPSP在对照动物和去神经支配动物的神经元中相似。然而，去神经支配的神经元在超极化电流脉冲或传入诱发的IPSP后常常表现出反弹去极化。在70%的去神经支配神经元中，谷氨酸受体拮抗剂可减少但不能消除突触诱发的反弹去极化。甘氨酸受体拮抗剂士的宁可消除这些神经元中与IPSP相关的去极化。总体而言，这些结果表明兴奋性传入纤维的功能性去神经支配会由于细胞丢失以及单个存活突触强度降低而降低其突触效能。
