NMDA receptors contribute to primary visceral afferent transmission in the nucleus of the solitary tract
NMDA receptors contribute to primary visceral afferent transmission in the nucleus of the solitary tract
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DOI：
10.1152/jn.1997.77.5.2539
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发表时间：
1997-05-01
影响因子：
2.5
通讯作者：
Bonham, AC
中科院分区：
文献类型：
--
作者：
Aylwin, ML;Horowitz, JM;Bonham, AC
孤束核（NTS）是协调自主神经反射控制的主要部位。该核接收并组织来自大血管、心脏、肺和胃肠器官的初级内脏（感觉）传入输入。谷氨酸是由初级传入纤维释放的兴奋性神经递质，激活NTS二级神经元上的非N-甲基-D-天冬氨酸（non-NMDA）受体。仍然存在的问题是，二级神经元上的NMDA受体是否也被激活。因此，本研究的目的是直接确定NMDA受体是否有助于初级内脏传入输入的二级神经元在NTS的突触传递。全细胞膜片钳记录从中间和尾部的NTS神经元在大鼠冠状延髓切片。刺激孤束（1-25 V，0.1 ms，0.2或0.5 Hz），在膜电位-90 ~+60 mV范围内诱发兴奋性突触后电流（EPSC）。在获得孤束诱发EPSC的电流-电压关系的32个神经元中，有28个神经元的电流具有短的起始延迟（3.42 +/- 1.03 ms，平均值+/- SD），表明它们是二级神经元单突触激活的结果。孤束诱发的EPSC既有快成分，也有慢成分。慢波振幅与电压呈非线性关系（仅在膜电位为-45 mV时显示），可被NMDA受体拮抗剂DL-2-氨基-5-单磷酸戊酸阻断（APV，50 μ M; n = 12; P = 0.0001），并在膜电位负至-45 mV时在标称无Mg 2+灌注液中增强（n = 5; P = 0.016），表明慢成分是由NMDA受体介导的。快成分的幅度与电压呈线性相关，并被非NMDA受体拮抗剂2，3-二羟基-6-硝基-7-氨磺酰基苯并（F）喹喔啉（NBQX，3 μ M; n = 9; P = 0.0014）阻断，表明快成分由非NMDA受体介导。NBQX不能阻断EPSC的慢成分（n = 6; P = 0.134），APV也不能阻断EPSC的快成分（n = 12; P = 0.124）。这些结果表明，NMDA受体和非NMDA受体共存于同一个二级NTS神经元，并介导初级内脏传入的NTS。NMDA受体的参与表明，在NTS的二级神经元可能有以前未认识到的自主神经功能的反射控制的综合能力。
The nucleus of the solitary tract (NTS) is a principal site for coordinating the reflex control of autonomic function. The nucleus receives and organizes primary visceral (sensory) afferent inputs from the great vessels, heart, lung, and gastrointestinal organs. Glutamate, the excitatory neurotransmitter released by the primary afferent fibers, activates non-N-methyl-D-aspartate (non-NMDA) receptors on second-order neurons in the NTS. Still in question is whether NMDA receptors on the second-order neurons are also activated. Accordingly, the purpose of this study was to directly determine whether NMDA receptors contribute to synaptic transmission of primary visceral afferent input to second-order neurons in the NTS. Whole cell patch-clamp recordings were obtained from intermediate and caudal NTS neurons in rat coronal medullary slices. Excitatory postsynaptic currents (EPSCs) were evoked by stimulation of the solitary tract (1-25 V, 0.1 ms, 0.2 or 0.5 Hz) at membrane potentials ranging from -90 to +60 mV. In 28 of 32 neurons in which current-voltage relationships were obtained for solitary-tract-evoked EPSCs, the currents had short onset latencies (3.42 +/- 1.03 ms, mean +/- SD), indicating that they were the result of monosynaptic activation of second-order neurons. Solitary-tract-evoked EPSCs had both a fast and a slow component. The amplitude of the slow component was nonlinearly related to voltage (being revealed only at membrane potentials positive to -45 mV), blocked by the NMDA receptor antagonist DL-2-amino-5-monophosphovaleric acid (APV, 50 mu M; n = 12; P = 0.0001), and enhanced in nominally Mg2+-free perfusate at membrane potentials negative to -45 mV (n = 5; P = 0.016), demonstrating that the slow component was mediated by NMDA receptors. The amplitude of the fast component was linearly related to voltage and blocked by the non-NMDA receptor antagonist 2,3- dihydroxy-6-nitro-7-sulfamoylbenzo (F)quinoxaline (NBQX, 3 mu M; n = 9; P = 0.0014), demonstrating that the fast component was mediated by non-NMDA receptors. The slow component of the EPSCs was not blocked by NBQX (n = 6; P = 0.134), nor was the fast component blocked by APV (n = 12; P = 0.124). These results show that both NMDA and non-NMDA receptors coexist on the same second-order NTS neurons and mediate primary visceral afferent transmission in the NTS. The participation of NMDA receptors suggests that second-order neurons in the NTS may have previously unrecognized integrative capabilities in the reflex control of autonomic function.