Lee H S, Chong W, Han S K, Lee M H, Ryu P D
Department of Veterinary Pharmacology, College of Veterinary Medicine, Seoul National University, 103 Seodun-dong Kwonsun-ku, 441-744, Suwon, South Korea.
Neuroscience. 2001;102(2):401-11. doi: 10.1016/s0306-4522(00)00490-5.
Glutamate is known to increase neuronal excitability in the subfornical organ, a circumventricular organ devoid of the blood-brain barrier. To understand the synaptic mechanism of neuronal excitation by glutamate in this nucleus, we examined the effects of glutamate on GABAergic spontaneous inhibitory postsynaptic currents recorded from subfornical organ neurons in the rat brain slice. The baseline frequency, amplitude and decay time-constant of such spontaneous synaptic currents were 5.60 Hz, 119 pA and 17.3 ms, respectively. Glutamate (10-1000 microM) selectively inhibited the frequency of spontaneous GABAergic inhibitory postsynaptic currents (half-maximal effective concentration=47 microM) with little effects on their amplitudes and decay time constants. The inhibitory effect of glutamate on the frequency of spontaneous GABAergic postsynaptic currents was not blocked by tetrodotoxin (1 microM), or by the antagonists of ionotropic glutamate receptors. In contrast, such inhibitory effect of glutamate was mimicked by general or group II selective metabotropic glutamate receptor agonists such as DCGIV (2S,1'R,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (half-maximal effective concentration=112 nM), but not by the agonists for group I or group III metabotropic glutamate receptors. Under current clamp mode, glutamate reduced the frequencies of spontaneous inhibitory postsynaptic potentials and action potentials in subfornical organ neurons. Our data indicate that glutamate decreases the frequency of spontaneous inhibitory postsynaptic currents by acting on the group II metabotropic glutamate receptors on axonal terminals in the subfornical organ. From these results we suggest that the glutamate-induced modulation of tonic GABAergic inhibitory synaptic activity can influence the excitability of subfornical organ neurons.
已知谷氨酸可增加穹窿下器（一种没有血脑屏障的室周器官）中的神经元兴奋性。为了解谷氨酸在此核团中引起神经元兴奋的突触机制，我们研究了谷氨酸对大鼠脑片中穹窿下器神经元记录到的GABA能自发性抑制性突触后电流的影响。这种自发性突触电流的基线频率、幅度和衰减时间常数分别为5.60 Hz、119 pA和17.3 ms。谷氨酸（10 - 1000 μM）选择性抑制自发性GABA能抑制性突触后电流的频率（半数最大效应浓度 = 47 μM），而对其幅度和衰减时间常数影响很小。谷氨酸对自发性GABA能突触后电流频率的抑制作用不受河豚毒素（1 μM）或离子型谷氨酸受体拮抗剂的阻断。相反，谷氨酸的这种抑制作用可被一般或II组选择性代谢型谷氨酸受体激动剂如DCGIV（2S,1'R,2'R,3'R）-2-（2',3'-二羧基环丙基）甘氨酸（半数最大效应浓度 = 112 nM）模拟，但不受I组或III组代谢型谷氨酸受体激动剂的模拟。在电流钳模式下，谷氨酸降低了穹窿下器神经元自发性抑制性突触后电位和动作电位的频率。我们的数据表明，谷氨酸通过作用于穹窿下器轴突终末上的II组代谢型谷氨酸受体来降低自发性抑制性突触后电流的频率。从这些结果我们推测，谷氨酸诱导的紧张性GABA能抑制性突触活动调节可影响穹窿下器神经元的兴奋性。
