Zaninetti M, Raggenbass M
Department of Physiology, University Medical Center, CH-1211 Geneva 4, Switzerland.
Eur J Neurosci. 2000 Nov;12(11):3975-84. doi: 10.1046/j.1460-9568.2000.00290.x.
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 gamma-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.
催产素可能在大鼠海马体中作为一种神经递质/神经调质发挥作用。催产素结合位点存在于海马下托和CA1区，且催产素能够激发一类CA1非锥体神经元。在本研究中，我们对催产素对海马体突触传递的影响进行了特征描述。在氯离子浓度几乎对称的条件下，从锥体神经元获得全细胞记录。选择性催产素受体激动剂[苏氨酸4，甘氨酸7]-催产素（TGOT）实际上在所有神经元中都引起了自发性抑制性突触后电流（IPSCs）频率和幅度的增加。这些肽增强的IPSCs被荷包牡丹碱阻断，但不被士的宁阻断，并且在接近0 mV时反转，表明它们是由γ-氨基丁酸（GABA）A受体介导的。平均而言，TGOT使自发性IPSCs的频率增加近三倍，幅度几乎翻倍。TGOT不影响微小IPSCs或自发性兴奋性突触后电流（EPSCs）的频率和幅度，并且对诱发的IPSCs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/或树突施加兴奋性作用来促进抑制性传递。在位于海马体不同层的中间神经元中进行了细胞外记录。将它们对TGOT的敏感性与P物质（SP）的敏感性进行了比较。锥体层中的中间神经元对TGOT和SP均有反应。相比之下，辐射层中间神经元对SP有反应，但对TGOT无反应。在原层中，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，对催产素敏感的中间神经元似乎优先位于锥体神经元附近。
