Oxytocin receptor agonists enhance inhibitory synaptic transmission in the rat hippocampus by activating interneurons in stratum pyramidale

Oxytocin receptor agonists enhance inhibitory synaptic transmission in the rat hippocampus by activating interneurons in stratum pyramidale
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催产素受体激动剂通过激活锥体层的中间神经元增强大鼠海马的抑制性突触传递

DOI:
10.1046/j.1460-9568.2000.00290.x
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发表时间:
2000
影响因子:
3.4
通讯作者:
M. Raggenbass
M. Raggenbass
中科院分区:
医学3区
文献类型:
--
作者:
M. Zaninetti;M. Raggenbass

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催产素可能在大鼠的海马区起到神经递质/神经调质的作用。催产素结合部位存在于下丘脑和CA1区,催产素可兴奋一类CA1非锥体神经元。在目前的工作中,我们研究了催产素对海马区突触传递的影响。全细胞记录从锥体神经元获得,在几乎对称的氯离子浓度条件下。选择性催产素受体激动剂[Thr4,Gly7]-催产素(TGOT)可引起几乎所有神经元自发性抑制性突触后电流(IPSCs)频率和幅度的增加。这些多肽增强的IPSCs可被荷包牡丹碱阻断,但不能被士的宁阻断,并在0 mV附近逆转,表明它们是由γ-氨基丁酸A受体介导的。平均而言,TGOT导致自发性IPSCs的频率增加近三倍,幅度增加近一倍。TGOT不影响小型IPSCs的频率和幅度,也不影响自发兴奋性突触后电流(EPSCs),对诱发的IPSCs也没有影响。该肽不影响锥体神经元的基本膜特性或其对GABA的敏感性。因此,TGOT通过对GABA能中间神经元的胞体和/或树突施加兴奋作用来促进抑制性传递。对位于不同海马层的中间神经元进行细胞外记录。比较它们对TGOT和P物质(SP)的敏感性。TGOT和SP均可兴奋锥体层的中间神经元。辐射层中间神经元对SP有反应,而对TGOT无反应。在东方层,一半的中间神经元对SP有反应,但只有少数对TGOT有反应。因此,催产素反应的中间神经元似乎优先位于锥体神经元附近。
Oxytocin probably plays a role as a neurotransmitter/neuromodulator in the hippocampus of the rat. Oxytocin binding sites are present in the subiculum and CA1 region and oxytocin can excite a class of CA1 nonpyramidal neurons. In the present work we characterized the effect of oxytocin on hippocampal synaptic transmission. Whole‐cell recordings were obtained from pyramidal neurons, in conditions of nearly symmetrical chloride concentrations. The selective oxytocin receptor agonist, [Thr4,Gly7]‐oxytocin (TGOT), caused an increase in the frequency and amplitude of spontaneous inhibitory postsynaptic currents (IPSCs) in virtually all neurons. These peptide‐enhanced IPSCs were blocked by bicuculline, but not by strychnine, and reversed near 0 mV, indicating that they were mediated by γ‐aminobutyric acid (GABA)A receptors. On average, TGOT caused a nearly threefold increase in the frequency and almost a doubling in the amplitude of spontaneous IPSCs. TGOT did not influence the frequency and the amplitude of miniature IPSCs or spontaneous excitatory postsynaptic currents (EPSCs), and had no effect on evoked IPSCs. The peptide did not affect the basic membrane properties of pyramidal neurons or their GABA sensitivity. Thus, TGOT facilitated inhibitory transmission by exerting an excitatory action on the soma and/or dendrites of GABAergic interneurons. Extracellular recordings were performed in interneurons located in various hippocampal strata. Their sensitivity to TGOT was compared to that of substance P (SP). Interneurons in stratum pyramidale were excited both by TGOT and by SP. By contrast, stratum radiatum interneurons responded to SP but not to TGOT. In stratum oriens, half of the interneurons responded to SP, but only a minority to TGOT. Thus, oxytocin‐responsive interneurons appear to be preferentially located in close vicinity of pyramidal neurons.
催产素的高选择性体外和体内子宫受体拮抗剂的设计和合成:与阿托西班的比较。
DOI: 10.1111/j.1399-3011.1995.tb00596.x
发表时间: 1995
期刊: International journal of peptide and protein research
影响因子: --
作者:
Manning,M;Miteva,K;Pancheva,S;Stoev,S;Wo,NC;Chan,WY
通讯作者: Chan,WY
DOI: 10.1021/jm00358a018
发表时间: 1983-01-01
影响因子: 7.3
作者:
GRZONKA, Z;LAMMEK, B;SCHWARTZ, IL
通讯作者: SCHWARTZ, IL
DOI: 10.1073/pnas.80.21.6713
发表时间: 1983
影响因子: 11.1
作者:
Mühlethaler,M;Sawyer,WH;Manning,MM;Dreifuss,JJ
通讯作者: Dreifuss,JJ