Synaptic α5 subunit-containing GABAA receptors mediate IPSPs elicited by dendrite-preferring cells in rat neocortex
Synaptic α5 subunit-containing GABAA receptors mediate IPSPs elicited by dendrite-preferring cells in rat neocortex
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DOI：
10.1093/cercor/bhm160
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发表时间：
2008-06-01
期刊：
影响因子：
3.7
通讯作者：
Thomson, Alex M.
中科院分区：
文献类型：
--
作者：
Ali, Afia B.;Thomson, Alex M.
先前的研究表明，一类脱发的海马间神经元通过Alpha 5γ-氨基丁酸（GABA（A）受体抑制锥体细胞，而含有alpha 2/3 gaba（A Alpha 1/3 Gaba（Alpha 2/3 gaba）（Alpha 1/3 gaba）（Alpha 2/3 gaba）（ ）受体分别。这项研究询问是否有选择性地插入了由新皮质抑制性突触中的不同α亚基GABA（A）受体，该突触受到特定类别的内神经元的支配。通过从少年大鼠的新皮层切片中的双重全细胞记录中，探索了3类神经元在新皮层金字塔细胞中抑制性突触后电位（IPSP）的苯二氮卓类药理（IPSP）（P18-23）。由α1优先激动剂的Zolpidem强大地增强了由具有狭窄尖峰和非适应发射模式激活的快速IPSP，其较大的Alpha 1 GABA（a）受体（a）比通过多极的激活的alpha 1 gaba（a）受体来强大增强。 Zolpidem强烈增强，但对Alpha 5选择性不敏感反激动剂iaalpha5（MSD，英国埃塞克斯），主要通过α2/3GABA（a）受体进行调解。相比之下，尽管宽光谱激动剂（Wizepam）增强了，但通过iaalpha5和锌降低了含锌和锌对唑吡坦不敏感的IPSPs，锌和锌不敏感。因此，在新皮质金字塔上突触的GABA（A）受体的插入是输入特异性的，近端抑制作用采用Alpha 1和Alpha 2/3 GABA（A）受体（A）受体和树突含量偏用的BITUFFRITE BITUFTED BITUFFTED BITUFFTED BITENERONE激活Alpha 5 Gaba（A）受体。
Previous studies indicated that one class of dendrite-preferring hippocampal interneurones inhibits pyramidal cells via alpha 5 gamma-aminobutyric acid (GABA(A)) receptors whereas parvalbumin- and CCK-containing basket cells act via alpha 1 and alpha 2/3 GABA(A) receptors, respectively. This study asked whether there is selective insertion of different alpha subunit-containing GABA(A) receptors at neocortical inhibitory synapses innervated by specific classes of interneurones. The benzodiazepine site pharmacology of inhibitory postsynaptic potentials (IPSPs) elicited in neocortical pyramidal cells by 3 classes of interneurones was explored with dual whole-cell recordings in neocortical slices from juvenile rats (P18-23). Fast IPSPs activated by multipolar interneurones with narrow spikes and nonadapting firing patterns were powerfully enhanced by the alpha 1-preferring agonist zolpidem, suggesting mediation via larger proportion of alpha 1 GABA(A) receptors than those activated by multipolar, adapting interneurones, which were less strongly enhanced by zolpidem, but equally insensitive to the alpha 5-selective inverse agonist IAalpha5 (MSD, Essex, UK) suggesting mediation predominantly via alpha 2/3 GABA(A) receptors. In contrast, the IPSPs elicited by bitufted, dendrite-preferring interneurones were reduced by IAalpha5 and by zinc and insensitive to zolpidem despite enhancement by the broad-spectrum agonist, diazepam. Thus insertion of GABA(A) receptors at synapses on neocortical pyramids is input-specific, with proximal inhibition employing alpha 1 and alpha 2/3 GABA(A) receptors and dendrite-preferring bitufted interneurones activating alpha 5 GABA(A) receptors.