Protracted postnatal development of inhibitory synaptic transmission in rat hippocampal area CA1 neurons
Protracted postnatal development of inhibitory synaptic transmission in rat hippocampal area CA1 neurons
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DOI：
10.1152/jn.2000.84.5.2465
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发表时间：
2000-11-01
影响因子：
2.5
通讯作者：
Coulter, DA
中科院分区：
文献类型：
--
作者：
Cohen, AS;Lin, DD;Coulter, DA
在中枢神经系统中，抑制性突触功能在出生后早期发育过程中经历了深刻的转变。这是由于突触下GABA（A）受体（GABA（A）Rs）的亚单位组成在不同发育阶段的变化以及其他因素。这些变化包括氯介导的电导的驱动力以及释放的神经递质的数量和/或裂缝寿命的变化。本研究旨在探讨海马CA 1区锥体神经元GABA能突触功能发育成熟的性质和时间过程。在新生儿[出生后第1-7天（P）]和未成熟（P8-14）CA 1神经元中，与更成熟神经元中记录的mIPSC相比，微型抑制性突触后电流（mIPSC）显著更大，频率更低，动力学更慢。成年mIPSC动力学在出生后第三周在CA 1神经元中实现。然而，尽管mIPSC动力学明显成熟，但在青春期（P15-21）神经元中变构激动剂对mIPSC的调节仍存在显著差异。地西泮（1-300 nM）和唑吡坦（200 nM）增加了青少年而非成年神经元中mIPSC的振幅。两种药物在两个年龄段均增加了mIPSC衰减时间。这些差异激动剂对mIPSC振幅的影响表明，在青少年CA 1神经元，抑制性突触的运作方式不同于成人突触和功能，好像突触下受体没有完全被GABA的量子释放所占据。从青少年神经元中提取的体周斑的快速激动剂应用实验为这一假设提供了额外的支持。在GABA（A）R电流记录在这些补丁，苯二氮卓类药物的振幅增强效应是明显的，只有当非饱和GABA浓度。此外，P15-21神经元中mIPSC的非稳态噪声分析显示，唑吡坦诱导的mIPSC增强不是由于突触下GABA（A）Rs的单通道电导增加，而是由于响应单个GABA量子的开放通道数量增加，进一步支持了突触受体在青春期神经元突触功能期间可能不饱和的假设。这些数据表明，抑制性突触传递经历了一个显着延长的出生后大鼠CA 1锥体神经元的成熟。在出生后的前两周，mIPSC幅度大，速度慢，很少发生。到出生后第三周，mIPSC在动力学上已经成熟，但对调节药物保留了不同的反应，这可能反映了突触结构和功能在青春期持续不成熟。
In the CNS, inhibitory synaptic function undergoes profound transformation during early postnatal development. This is due to variations in the subunit composition of subsynaptic GABA(A) receptors (GABA(A)Rs) at differing developmental stages as well as other factors. These include changes in the driving force for chloride-mediated conductances as well as the quantity and/or cleft lifetime of released neurotransmitter. The present study was undertaken to investigate the nature and time course of developmental maturation of GABAergic synaptic function in hippocampal CA1 pyramidal neurons. In neonatal [postnatal day (P) 1-7] and immature (P8-14) CA1 neurons, miniature inhibitory postsynaptic currents (mIPSCs) were significantly larger, were less frequent, and had slower kinetics compared with mIPSCs recorded in more mature neurons. Adult mIPSC kinetics were achieved by the third postnatal week in CA1 neurons. However, despite this apparent maturation of mIPSC kinetics, significant differences in modulation of mIPSCs by allosteric agonists in adolescent (P15-21) neurons were still evident. Diazepam (1-300 nM) and zolpidem (200 nM) increased the amplitude of mIPSCs in adolescent but not adult neurons. Both drugs increased mIPSC decay times equally at both ages. These differential agonist effects on mIPSC amplitude suggest that in adolescent CA1 neurons, inhibitory synapses operate differently than adult synapses and function as if subsynaptic receptors are not fully occupied by quantal release of GABA. Rapid agonist application experiments on perisomatic patches pulled from adolescent neurons provided additional support for this hypothesis. In GABA(A)R currents recorded in these patches, benzodiazepine amplitude augmentation effects were evident only when nonsaturating GABA concentrations were applied. Furthermore nonstationary noise analysis of mIPSCs in P15-21 neurons revealed that zolpidem-induced mIPSC augmentation was not due to an increase in single-channel conductance of subsynaptic GABA(A)Rs but rather to an increase in the number of open channels responding to a single GABA quantum, further supporting the hypothesis that synaptic receptors may not be saturated during synaptic function in adolescent neurons. These data demonstrate that inhibitory synaptic transmission undergoes a markedly protracted postnatal maturation in rat CA1 pyramidal neurons. In the first two postnatal weeks, mIPSCs are large in amplitude, are slow, and occur infrequently. By the third postnatal week, mIPSCs have matured kinetically but retain distinct responses to modulatory drugs, possibly reflecting continued immaturity in synaptic structure and function persisting through adolescence.