Vasopressin inhibits glutamate release via two distinct modes in the brainstem
Vasopressin inhibits glutamate release via two distinct modes in the brainstem
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DOI：
10.1523/jneurosci.5176-05.2006
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发表时间：
2006-06-07
影响因子：
5.3
通讯作者：
Andresen, Michael C.
中科院分区：
文献类型：
--
作者：
Bailey, Timothy W.;Jin, Young-Ho;Andresen, Michael C.
下丘脑通过内侧孤束核释放的精氨酸抗利尿激素（AVP）协调自主神经反应。然而，AVP在NTS通路中的作用机制和位置尚不确定。在脑干切片中，我们激活孤立束（ST）初级传入神经释放谷氨酸，并测试AVP是否调节突触传递到二级神经元。根据ST突触特征或来自外周压力感受器传入的顺行示踪剂的存在，NTS神经元被分类为二级。刺激募集曲线显示单个ST轴突刺激可诱发单个神经元上的ST- epscs。单个神经元中ST-EPSCs的方差均值（V-M）分析显示，平均19个释放位点(N)的释放概率一致较高（p相似于0.9），量子大小(q)为34.0 +/- 4.7 pA。在49个神经元中的26个中，AVP抑制传入突触传递。在大多数神经元中，AVP通过将p降低至0.65来降低ST-EPSC振幅（n = 20），而q、n和传导时间不受影响。单独使用V1a拮抗剂SR49059可降低ST-EPSC V，增加M，提示补性AVP作用，阻断外源性AVP作用（n = 4）。在其他具有相同ST释放特性的神经元中，AVP诱导突触失效并增加传导时间，但未改变成功ST- epsc的V-M关系（n = 6）。有趣的是，频率抑制的ST-EPSCs不受AVP的影响。AVP不能改变保持或电压依赖的钾电流。因此，AVP通过两种不同的新型状态依赖机制调节NTS神经元：一种是对末端谷氨酸释放的类似的分级突触前抑制，另一种是传导兴奋的二进制外阻断。
The hypothalamus coordinates autonomic responses in part through arginine vasopressin (AVP) released in medial nucleus tractus solitarius (NTS). However, the mechanisms and sites of AVP action within NTS pathways are uncertain. In brainstem slices, we activated solitary tract (ST) primary afferents to release glutamate and tested whether AVP modulated synaptic transmission to second-order neurons. NTS neurons were classified as second order by ST synaptic characteristics or the presence of anterograde tracers from peripheral baroreceptor afferents. Stimulus recruitment curves indicated ST-EPSCs on individual neurons were evoked by stimulation of single ST axons. Variance-mean (V-M) analysis of ST-EPSCs in individual neurons revealed uniformly high release probability (p similar to 0.9) from an average of 19 release sites (N) and a quantal size (q) of 34.0 +/- 4.7 pA. In 26 of 49 neurons, AVP inhibited afferent synaptic transmission. In most neurons, AVP reduced ST-EPSC amplitudes (n = 20) by decreasing p to 0.65, whereas q, N, and conduction times were unaffected. The V1a antagonist SR49059 alone decreased ST-EPSC V and increased M, suggesting tonic AVP actions, and blocked exogenous AVP action (n = 4). In other neurons with identical ST release properties, AVP induced synaptic failures and increased conduction time without altering the V-M relationship of successful ST-EPSCs ( n = 6). Interestingly, frequency-depressed ST-EPSCs were not affected by AVP. AVP failed to alter holding or voltage-dependent potassium currents. Thus, AVP regulates NTS neurons by two distinct novel and state-dependent mechanisms: one, an analog, graded presynaptic inhibition of terminal glutamate release and the other, a binary, extraterminal block of conducted excitation.