Schmahl C, Böhmer G
Institute of Physiology and Pathophysiology, Johannes Gutenberg University, Mainz, Germany.
Brain Res. 1997 Jan 23;746(1-2):151-63. doi: 10.1016/s0006-8993(96)01220-6.
Effects of L-glutamate, AMPA, NMDA and NPY on the discharge activity of neurons located in the ventral subdivision of the suprachiasmatic nucleus were examined in submerged coronal slices of the rat hypothalamus. All substances were bath applied. Application of L-glutamate (14 neurons examined) induced an excitatory response in 8 suprachiasmatic neurons (+248.9 +/- 122.24%, mean +/- S.E.M.; P < 0.001). A biphasic response, i.e. an initial transient excitation (+54.3 +/- 8.21%; P < 0.001) succeeded by an inhibition (-66.2 +/- 9.31%; P < 0.001), was observed in 6 neurons. Application of AMPA (36 neurons examined) resulted in an excitation of 31 neurons (+209.2 +/- 58.58%; P < 0.0001). Application of NMDA (57 neurons examined) induced an excitation in 34 neurons (+253.8 +/- 91.18%; P < 0.0001), but an inhibition in 8 neurons (-757 +/- 6.52; P < 0.0001). Biphasic effects of NMDA with an excitatory component (+58.7 +/- 9.94%; P < 0.0001) succeeded by an inhibitory component (-62.0 +/- 8.07%; P < 0.0001) were observed in 13 neurons. In 5 of 13 examined cases, the inhibitory component of neuronal responses to NMDA was significantly attenuated by the simultaneous application of strychnine (attenuation was 56%; P < 0.05). The application of NPY (40 neurons examined) induced significant effects on the discharge rate of 29 suprachiasmatic neurons. 18 of these neurons were inhibited (-59.3 +/- 6.39%; P < 0.0001) whereas 11 neurons were excited (+156.6 +/- 107.222%; P < 0.001) by NPY. In 8 of 11 neurons examined, the NPY-induced inhibition was significantly attenuated by 92% during simultaneous application of strychnine (P < 0.001). In 23 NPY-sensitive neurons, the discharge activity was also affected by NMDA. Neurons excited by NPY were also excited by NMDA (8 cells). In neurons inhibited by NPY, application of NMDA induced either an inhibition (3 cells) an excitation (5 cells) or a biphasic effect (7 cells). Results suggest a direct excitatory effect of AMPA, NMDA and NPY on suprachiasmatic neurons. In contrast, inhibitory actions of NMDA and NPY are considered induced by an activation of inhibitory interneurons. Antagonistic effects of strychnine suggest an involvement of glycinergic interneurons in a subpopulation of neurons inhibited by NMDA and in most neurons inhibited by NPY. The involvement of inhibitory mechanisms in photic entrainment of the circadian system is discussed. An integrative model of excitatory and inhibitory actions of EAA and NPY on suprachiasmatic neurons is proposed.
在大鼠下丘脑冠状切片中，研究了L-谷氨酸、α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）、N-甲基-D-天冬氨酸（NMDA）和神经肽Y（NPY）对位于视交叉上核腹侧亚区神经元放电活动的影响。所有物质均采用浴槽给药。给予L-谷氨酸（检测了14个神经元）后，8个视交叉上神经元出现兴奋反应（+248.9±122.24%，平均值±标准误；P<0.001）。在6个神经元中观察到双相反应，即初始短暂兴奋（+54.3±8.21%；P<0.001）后接着是抑制（-66.2±9.31%；P<0.001）。给予AMPA（检测了36个神经元）使31个神经元兴奋（+209.2±58.58%；P<0.0001）。给予NMDA（检测了57个神经元）使34个神经元兴奋（+253.8±91.18%；P<0.0001），但使8个神经元抑制（-757±6.52；P<0.0001）。在13个神经元中观察到NMDA的双相效应，先是兴奋成分（+58.7±9.94%；P<0.0001），接着是抑制成分（-62.0±8.07%；P<0.0001）。在13个检测案例中的5个中，同时应用士的宁可显著减弱神经元对NMDA反应的抑制成分（减弱56%；P<0.05）。给予NPY（检测了40个神经元）对29个视交叉上神经元的放电频率产生显著影响。其中18个神经元被抑制（-59.3±6.39%；P<0.0001），而11个神经元被NPY兴奋（+156.6±107.222%；P<0.001）。在检测的11个神经元中的8个中，同时应用士的宁期间，NPY诱导的抑制显著减弱了92%（P<0.001）。在23个对NPY敏感的神经元中，放电活动也受NMDA影响。被NPY兴奋的神经元也被NMDA兴奋（8个细胞）。在被NPY抑制的神经元中，应用NMDA诱导出抑制（3个细胞）兴奋（5个细胞）或双相效应（7个细胞）。结果表明AMPA、NMDA和NPY对视交叉上神经元有直接兴奋作用。相反，NMDA和NPY的抑制作用被认为是由抑制性中间神经元的激活所诱导。士的宁的拮抗作用表明甘氨酸能中间神经元参与了受NMDA抑制的神经元亚群以及大多数受NPY抑制的神经元。讨论了抑制机制在昼夜节律系统光同步中的作用。提出了兴奋性氨基酸（EAA）和NPY对视交叉上神经元兴奋和抑制作用的整合模型。
