Long-term potentiation and functional synapse induction in developing hippocampus

Long-term potentiation and functional synapse induction in developing hippocampus
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DOI:
10.1038/381071a0
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发表时间:
1996-05-02
期刊:
影响因子:
64.8
通讯作者:
Konnerth, A
Konnerth, A
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Durand, GM;Kovalchuk, Y;Konnerth, A

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长期增强(LTP)是一种细胞机制,可能是学习和记忆的基础(1)。为了验证LTP参与活动依赖性突触形成的假设,我们结合了全细胞记录和共聚焦显微镜,以研究海马神经元突触在其最早的发展阶段。在这里,我们报告说,在出生后的第一周,海马神经元网络逐渐成为功能性的前体,纯NMDA(N-甲基-D-天冬氨酸)受体为基础的突触接触到进行AMPA(α-氨基-3-羟基-甲基异恶唑-4-丙酸)/NMDA受体型突触的转变。这种功能性突触诱导是由LTP的联合形式引起的,因此它是输入特异性的,并且很容易通过将突触前刺激与突触后去极化配对来触发。我们的研究结果挑战了以前的观点,即LTP只发生在海马体发育的后期(2-6),其诱导需要树突棘(7)。他们还提供了直接的证据,LTP是重要的活动依赖性的形成传导性突触在发育中的哺乳动物大脑。
LONG-TERM potentiation (LTP) is a cellular mechanism that potentially underlies learning and memory(1). To test the hypothesis that LTP is involved in activity-dependent synapse formation, we combined whole-cell recordings and confocal microscopy to investigate hippocampal glutamatergic synapses at their earliest stages of development. Here we report that, during the first postnatal week, the hippocampal glutamatergic network becomes gradually functional owing to the transformation of precursor, pure NMDA (N-methyl-D-aspartate)-receptor-based synaptic contacts into conducting AMPA (alpha-amino-3-hydroxyd-methylisoxazole-4-proprionate)/NMDA-receptor-type synapses. This functional synapse induction is caused by an associative form of LTP, so it is input-specific and easily triggered experimentally by pairing presynaptic stimulation with postsynaptic depolarization. Our results challenge previous views that LTP occurs in the hippocampus only at later stages of development(2-6) and that its induction requires dendritic spines(7). They also provide direct evidence that LTP is important for the activity-dependent formation of conducting glutamatergic synapses in the developing mammalian brain.