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钙通透性 AMPA 受体为不同海马中间神经元类型谷氨酸能突触长时程增强提供了一个共同的机制。

Calcium-permeable AMPA receptors provide a common mechanism for LTP in glutamatergic synapses of distinct hippocampal interneuron types.

机构信息

Department of Pharmacology, Oxford University, Oxford OX1 3QT, United Kingdom.

出版信息

J Neurosci. 2012 May 9;32(19):6511-6. doi: 10.1523/JNEUROSCI.0206-12.2012.

Abstract

Glutamatergic synapses on some hippocampal GABAergic interneurons exhibit activity-induced long-term potentiation (LTP). Interneuron types within the CA1 area expressing mutually exclusive molecular markers differ in LTP responses. Potentiation that depends on calcium-permeable (CP) AMPA receptors has been characterized in oriens-lacunosum moleculare (O-LM) interneurons, which express parvalbumin and somatostatin (SM). However, it is unknown how widely CP-AMPAR-dependent plasticity is expressed among different GABAergic interneuron types. Here we examine synaptic plasticity in rat hippocampal O-LM cells and two other interneuron types expressing either nitric oxide synthase (NOS) or cholecystokinin (CCK), which are known to be physiologically and developmentally distinct. We report similar CP-AMPAR-dependent LTP in NOS-immunopositive ivy cells and SM-expressing O-LM cells to afferent fiber theta burst stimulation. The potentiation in both cell types is induced at postsynaptic membrane potentials below firing threshold, and induction is blocked by intense spiking simultaneously with afferent stimulation. The strong inward rectification and calcium permeability of AMPARs is explained by a low level of GluA2 subunit mRNA expression. LTP is not elicited in CCK-expressing Schaffer collateral-associated cells, which lack CP-AMPARs and express high levels of the GluA2 subunit. The results show that CP-AMPAR-mediated synaptic potentiation is common in hippocampal interneuron types and occurs in interneurons of both feedforward and feedback inhibitory pathways.

摘要

谷氨酸能突触在一些海马 GABA 能中间神经元上表现出活动诱导的长期增强 (LTP)。在 CA1 区内表达相互排斥的分子标记的中间神经元类型在 LTP 反应中存在差异。已经在表达囊泡蛋白和生长抑素 (SM) 的齿状回-分子层 (O-LM) 中间神经元中描述了依赖于钙通透性 (CP) AMPA 受体的增强作用。然而,CP-AMPAR 依赖性可塑性在不同 GABA 能中间神经元类型中的表达程度尚不清楚。在这里,我们研究了大鼠海马 O-LM 细胞和另外两种表达一氧化氮合酶 (NOS) 或胆囊收缩素 (CCK) 的中间神经元类型的突触可塑性,已知这两种中间神经元在生理和发育上是不同的。我们报告了在 NOS 免疫阳性的常春藤细胞和表达 SM 的 O-LM 细胞中,类似的 CP-AMPAR 依赖性 LTP 对传入纤维的 theta 爆发刺激。在这两种细胞类型中,增强作用发生在突触后膜电位低于放电阈值时,并且在传入刺激的同时强烈放电会阻止诱导。AMPA 受体的强内向整流和钙通透性可以用 GluA2 亚基 mRNA 表达水平低来解释。在表达 CCK 的 Schaffer 侧支相关细胞中不会引发 LTP,这些细胞缺乏 CP-AMPARs 并表达高水平的 GluA2 亚基。结果表明,CP-AMPAR 介导的突触增强作用在海马中间神经元类型中很常见,并且发生在前馈和反馈抑制途径的中间神经元中。

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