ORPHANIN FQ OPIOID INTERACTIONS IN MODULATING SYNAPTIC PLASTICITY

孤啡肽-阿片相互作用在突触可塑性调节中的作用 1.进一步研究孤啡肽FQ对突触传递的影响 齿状回中的LTP。将讨论以下问题； A.孤儿FQ是否同时抑制外侧和内侧穿支的LTP 路径？ 孤啡肽能拮抗阿片类药物诱导的LTP易化作用吗？ 侧穿通径？ C.孤儿会干扰LTP的哪个阶段，是诱导阶段还是维持阶段 FQ？ 内源性孤啡肽FQ是否在LTP的调节中起作用？ 确定孤啡肽是否能拮抗阿片类药物诱导的去抑制作用。 A.孤啡肽FQ能否抑制突触传递和LTP GABAA的对抗者？ 孤儿FQ是否增强GABA能抑制性突触后电流 (IPSCs)齿状颗粒细胞还是促进IPSCs的LTP？ C.孤啡肽FQ能否作用于GABA能终末从而影响单突触IPSCs 颗粒细胞？ D.孤啡肽能拮抗阿片类药物在胞体引起的超极化吗 齿状GABA能中间神经元。 齿状体内GABA能中间神经元是否表达ORL-1免疫反应？ 如果是，ORL-1免疫反应的位置是否支持 孤啡肽FQ对中间神经元胞体或轴突的可能影响 终点站？ 3.孤啡素FQ抑制齿状回NMDA通道电流 颗粒细胞。 A.孤啡肽是否抑制NMDA受体介导的兴奋性突触后突触 齿状颗粒细胞诱发的电流(EPSCs)？ B.孤啡肽FQ是否抑制局部应用的膜电流 NMDA？ 4.观察孤啡肽是否能减少突触前谷氨酸的释放。 A.孤啡肽能否在没有海藻氨酸/AMPA受体介导的情况下抑制EPSCs 改变颗粒细胞对局部应用红藻氨酸的反应。 B.孤啡素FQ是否能降低自发性微型EPSCs的发生频率 颗粒细胞。 C.孤啡肽FQ能否降低K+诱导的、钙依赖的谷氨酸 海马片。

Orphanin FQ-Opioid InteractIons in Modulating Synaptic Plasticity 1. To further examine the effect of orphanin FQ on synaptic transmission and LTP in the dentate gyrus. The following questions will be addressed; a. Does orphanin FQ inhibit LTP in both the lateral and medial perforant path? b. Can orphanin FQ antagonize m opioid-induced facilitation of LTP in the lateral perforant path? c. Which phase of LTP, induction or maintenance, is interfered by orphanin FQ? d. Does endogenous orphanin FQ play a role in the modulation of LTP? To determine if orphanin FQ can antagonize opioid-induced disinhibition. a. Can orphanin FQ inhibit synaptic transmission and LTP in the presence of GABAA antagonists? b. Does orphanin FQ enhance GABAergic inhibitory postsynaptic currents (IPSCs) of dentate granule cells or facilitate LTP of IPSCs? c. Can orphanin FQ act on GABAergic terminals to affect monosynaptic IPSCs of granule cells? d. Can orphanin FQ antagonize opioid-induced hyperpolarization at the soma of dentate GABAergic interneurons. e. Is ORL-1 immunoreactivity expressed by dentate GABAergic interneurons? If they are, does the location of ORL-1 immunoreactivity support a possible effect of orphanin FQ on the interneuron soma or their axon terminals? 3. To examine it orphanin FQ inhibits NMDA channel currents in dentate granule cells. a. Does orphanin FQ depress NMDA receptor-mediated excitatory postsynaptic currents (EPSCs) evoked in dentate granule cells? b. Does orphanin FQ depress membrane currents induced by locally applied NMDA? 4. To examine if orphanin FQ reduces presynaptic glutamate release. a. Can orphanin FQ inhibit kainate/AMPA receptor mediated EPSCs without changing granule cell responses to locally applied kainate. b. Does orphanin FQ reduce the frequency of spontaneous miniature EPSCs in granule cells. c. Can orphanin FQ reduce K+-induced, Ca2+ -dependent glutamate from hippocampal slices.