Regulation of inhibitory synaptic transmission by vasoactive intestinal peptide (VIP) in the mouse suprachiasmatic nucleus
Regulation of inhibitory synaptic transmission by vasoactive intestinal peptide (VIP) in the mouse suprachiasmatic nucleus
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DOI：
10.1152/jn.00332.2003
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发表时间：
2003-09-01
影响因子：
2.5
通讯作者：
Colwell, CS
中科院分区：
文献类型：
--
作者：
Itri, J;Colwell, CS
哺乳动物的昼夜节律性是由下丘脑前部的一对核-视交叉上核(SCN)产生的，其神经元表达各种神经肽，这些神经肽被认为在昼夜节律系统中发挥重要作用。为探讨血管活性肠肽(VIP)对SCN神经元间抑制性突触传递的影响，我们采用全细胞膜片钳记录技术制作了小鼠SCN急性脑片。基线自发GABA能抑制突触后电流(IPSCs)在不同区域和不同时相之间存在显著差异，在夜间早些时候在背内侧区域观察到IPSCs的频率较高。VIP浴可使自发抑制性突触后电流(SIPSC)频率明显增加，且呈可逆性和剂量依赖性，对平均波幅和动力学参数无明显影响。VIP的作用广泛分布于整个SCN，在腹外侧区(VL)和背内侧区(DM)均可观察到。在河豚毒素存在的情况下，VIP增加了微型IPSCs的频率，而不影响平均幅度或动力学参数。VIP增强的幅度白天明显大于夜间。VIP-PACAP受体拮抗剂[Ac-Tyr(1)，D-Phe(2)]-GHRF 1-29或选择性VPAC(2)受体拮抗剂PG 99-465可完全阻断VIP的增强作用。VIP的作用似乎是通过cAMP/PKA依赖的机制介导的，就像Forsklin模拟的那样，而PKA拮抗剂H-89阻断了观察到的GABA电流的增强。我们的数据表明，VIP激活突触前VPAC(2)受体来调节SCN内的抑制性突触传递，这种作用因昼夜而异。
Circadian rhythmicity in mammals is generated by a pair of nuclei in the anterior hypothalamus known as the suprachiasmatic nuclei (SCN), whose neurons express a variety of neuropeptides that are thought to play an important role in the circadian timing system. To evaluate the influence of VIP on inhibitory synaptic transmission between SCN neurons, we used whole cell patch-clamp recording in an acute brain slice preparation of mouse SCN. Baseline spontaneous GABAergic inhibitory postsynaptic currents (IPSCs) varied significantly between regions and across phases, with a greater frequency of IPSCs observed in the dorsomedial region during the early night. Bath-applied VIP caused a significant increase in the frequency of spontaneous inhibitory postsynaptic currents (sIPSC) in a reversible and dose-dependent manner with no effect on the mean amplitude or kinetic parameters. The effect of VIP was widespread throughout the SCN and observed in both ventrolateral (VL) and dorsomedial (DM) regions. In the presence of tetrodotoxin, VIP increased the frequency of miniature IPSCs without affecting the mean magnitude or kinetic parameters. The magnitude of the enhancement by VIP was significantly larger during the day than during the night. Pretreatment with the VIP-PACAP receptor antagonist [Ac-Tyr(1), D-Phe(2)]- GHRF 1-29 or the selective VPAC(2) receptor antagonist PG 99-465 completely blocked the VIP-induced enhancement. The effect of VIP appears to be mediated by a cAMP/PKA-dependent mechanism as forskolin mimics, while the PKA antagonist H-89 blocks the observed enhancement of GABA currents. Our data suggest that VIP activates presynaptic VPAC(2) receptors to regulate inhibitory synaptic transmission within the SCN and that this effect varies from day to night.