Differential regulation of metabotropic glutamate receptor- and AMPA receptor-mediated dendritic Ca2+ signals by presynaptic and postsynaptic activity in hippocampal Interneurons

Differential regulation of metabotropic glutamate receptor- and AMPA receptor-mediated dendritic Ca2+ signals by presynaptic and postsynaptic activity in hippocampal Interneurons
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DOI:
10.1523/jneurosci.4388-04.2005
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发表时间:
2005-01-26
影响因子:
5.3
通讯作者:
Lacaille, JC
Lacaille, JC
中科院分区:
医学1区
文献类型:
--
作者:
Topolnik, L;Congar, P;Lacaille, JC

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钙作为普遍存在的第二信使发挥着至关重要的作用,并且对神经元突触可塑性的多种形式具有关键影响。海马中间神经元树突状 Ca2+ 信号的时空特性相对尚未被探索。在这里,我们使用双光子钙成像和全细胞记录来研究由不同谷氨酸受体介导的树突状 Ca2+ 信号的特性及其通过大鼠海马东方/肺叶 (O/A) 中间神经元突触活动的调节。我们证明 O/A 中间神经元表达 Ca2+-可渗透性 AMPA 受体 (CP-AMPAR),提供快速的 Ca2+ 信号。 O/A 细胞还可以在同一细胞中共表达 CP-AMPAR、Ca2+ 不可渗透的 AMPAR (CI-AMPAR) 和 I/II 类代谢型谷氨酸受体 (mGluR)(包括 mGluR1a)。 CI-AMPAR 通常与 mGluR 相关,从而产生比 CP-AMPAR 介导的反应更持久的 Ca2+ 信号。最后,CP-AMPAR-和mGluR-介导的Ca2+信号表现出明显的电压依赖性,并受到突触前和突触后活动的差异调节:弱突触刺激产生由CP-AMPAR介导的Ca2+信号,而较强的刺激或弱刺激与突触后去极化相结合,募集由mGluRs介导的Ca2+信号。我们的结果表明,空间受限的树突微域内特定谷氨酸受体介导的 Ca2+ 信号的差异激活可能具有不同的信号传导功能,并赋予东方/肺间神经元多种形式的 Ca2+ 介导的突触可塑性。通过一致的突触前和突触后活动特异性激活 mGluR 介导的 Ca2+ 信号满足了 Hebbian 配对的条件,并且可能是它们在 O/A 中间神经元突触的长期增强诱导中的重要作用的基础。
Calcium plays a crucial role as a ubiquitous second messenger and has a key influence in many forms of synaptic plasticity in neurons. The spatiotemporal properties of dendritic Ca2+ signals in hippocampal interneurons are relatively unexplored. Here we use two- photon calcium imaging and whole- cell recordings to study properties of dendritic Ca2+ signals mediated by different glutamate receptors and their regulation by synaptic activity in oriens/ alveus ( O/ A) interneurons of rat hippocampus. We demonstrate that O/ A interneurons express Ca2+- permeable AMPA receptors ( CP- AMPARs) providing fast Ca2+ signals. O/ A cells can also coexpress CP- AMPARs, Ca2+ -impermeable AMPARs ( CI- AMPARs), and group I/ II metabotropic glutamate receptors ( mGluRs) ( including mGluR1a), in the same cell. CI- AMPARs are often associated with mGluRs, resulting in longer- lasting Ca2+ signals than CP- AMPAR- mediated responses. Finally, CP- AMPAR- and mGluR- mediated Ca2+ signals demonstrate distinct voltage dependence and are differentially regulated by presynaptic and postsynaptic activity: weak synaptic stimulation produces Ca2+ signals mediated by CP- AMPARs, whereas stronger stimulation, or weak stimulation coupled with postsynaptic depolarization, recruits Ca2+ signals mediated by mGluRs. Our results suggest that differential activation of specific glutamate receptor- mediated Ca2+ signals within spatially restricted dendritic microdomains may serve distinct signaling functions and endow oriens/ alveus interneurons with multiple forms of Ca2+- mediated synaptic plasticity. Specific activation of mGluR- mediated Ca2+ signals by coincident presynaptic and postsynaptic activity fulfills the conditions for Hebbian pairing and likely underlies their important role in long- term potentiation induction at O/ A interneuron synapses.