去甲肾上腺素对腹外侧视前区神经元的作用途径研究

The pathway exploration of noradrenalin effects on two type neurons in the ventrolateral preoptic area

目的研究去甲肾上腺素(NA)对腹外侧视前区(VLPO)中两种类型神经元(促睡眠神经元和中间神经元)的作用途径。方法采用全细胞膜片钳技术,通过药理学方法在C57BL/6小鼠脑片上,研究NA对VLPO中两种类型神经元兴奋或抑制作用的途径。通过RT-PCR鉴定VLPO脑区NMDA受体表达的类型。结果电生理结果显示,NA(100μmol/L)对VLPO中间神经元的兴奋作用能被NMDA受体阻断剂(AP5)阻断(P<0.05,n=8),不能被AMPA受体阻断剂(CNQX)和γ-氨基丁酸受体阻断剂阻断。NA(100μmol/L)对VLPO促睡眠神经元的抑制作用均不能被AP5、CNQX和氟马西尼(flumazenil)阻断。RT-PCR结果显示NMDA受体的3种亚型(GluN2A、GluN2B、GluN1)在VLPO中均有表达。结论NA对VLPO中间神经元的兴奋作用是通过谷氨酸能神经元释放谷氨酸引起的间接效应,该兴奋效应由VLPO中间神经元上的NMDA受体介导。

Objective To study the pathway of noradrenalin(NA)effects on two type neurons(sleep-promoting neurons,interneurons)in the ventrolateral preoptic area(VLPO).Methods The whole cell patch clamp technique and pharmacological methods were used to analyze the pathway of NA excitating or inhibiting effects on the two type neurons in the VLPO.The types of NMDA receptor expressions in VLPO were identified by RT-PCR.Results Electrophysiological results showed that the excitatory effects of NA(100μmol/L)on VLPO interneurons were blocked by NMDA receptor blocker(AP5)(P<0.05,n=8),but not by AMPA receptor(CNQX)and GABA receptor blocker.The inhibitory effects of NA(100μmol/L)on the sleep-promoting neurons of VLPO were not blocked by AP5,CNQX or flumazenil.RT-PCR results showed that three subtypes of NMDA receptor(GluN2A,GluN2B,GluN1)were expressed in VLPO.Conclusion The excitatory effects of NA on VLPO interneurons is an indirect effects caused by glutamatergic neurons releasing glutamate,which is mediated by NMDA receptor of VLPO interneurons.