SYNAPTIC RESPONSES OF GUINEA-PIG CINGULATE CORTICAL-NEURONS INVITRO
SYNAPTIC RESPONSES OF GUINEA-PIG CINGULATE CORTICAL-NEURONS INVITRO
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DOI：
10.1152/jn.1991.65.4.822
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发表时间：
1991-04-01
影响因子：
2.5
通讯作者：
NISHI, S
中科院分区：
文献类型：
--
作者：
HIGASHI, H;TANAKA, E;NISHI, S
1.记录豚鼠前扣带回V/VI层神经元的细胞内记录，研究电刺激皮质下白质诱发的突触后电位(PSPs)。在正常生理条件下，记录到四种不同类型的PSP：6-氰基-7-硝基-2，3-二酮(CNQX)敏感的兴奋性突触后电位(EPSP)和荷包牡丹碱或苦参碱敏感的去极化或超极化的抑制性突触后电位(IPSP)，然后是对苯氯芬敏感的、持久的超极化突触后电位(LPSP)。EPSP、去极化和超极化IPSP和LPSP的平均峰值时间分别为10、22、28和146ms。在CNQX和荷包牡丹碱存在的情况下，高强度电刺激可引起持续时间更长的EPSP，峰值时间为21ms。EPSP的幅度和时程随膜超极化而减小，随膜去极化而增大。D，L-2-氨基-5-膦戊酸(D，L-APV)可逆性地取消EPSP。CNQX明显抑制荷包牡丹碱或印防己毒素敏感的去极化和超极化IPSP和苯氯芬敏感的LPSP，提示谷氨酸和/或天冬氨酸神经末梢投射到GABA能中间神经元，GABA能中间神经元主要由非N-甲基-D-天冬氨酸(Non-NMDA)受体激活。在印防己毒素存在下，复合EPSP的平均翻转电位为0 mV，与Glu引起的去极化的平均翻转电位(-6 mV)相似。在低浓度D，L-APV溶液中，去极化和超极化IPSP的平均翻转电位分别为-62 mV、-72 mV、-70 mV和-61 mV。因此，去极化IPSP的值与GABA的晚期反应的值相似，而超极化的IPSP的值与GABA的早期反应的值几乎相同。LPSP的平均翻转电位为-90 mV，与巴氯芬引起的超极化的-93 mV和棘波后超极化的-94 mV相似。应用苯氯芬可缩短自发放电的棘波间期，并逆转皮层下刺激后棘波间期的增加。这一结果表明，即使在切片制备中，前扣带回神经元也受到自发激活的GABA能神经元间的紧张性抑制控制。应用较高浓度的荷包牡丹碱或印防己毒素，或清除细胞外的镁离子，可导致自发的和诱发的癫痫样爆发放电。Co2+、CNQX、D，L-APV、有机钙拮抗剂、氟桂利嗪或低钙高镁介质均可可逆地阻断这种放电。应用Glu或NMDA可引起去极化和延长的超极化。奎斯奎宁(Quisquate，Quis)有类似的作用，而alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate(AMPA)或海人藻酸(Kainate)则没有。膜电位为-94 mV时，谷氨酸后超极化的极性发生反转。进一步的分析表明，NMDA受体激活过程中的少量钙离子进入会引起细胞内钙离子的释放，进而激活钙依赖的钾离子传导。这些结果表明，前扣带回神经元受到GABA能中间神经元的强烈抑制控制。
1. Intracellular recordings were made from layer V/VI neurons of the guinea pig anterior cingulate cortex to investigate postsynaptic potentials (PSPs) evoked by electrical stimulation of the subcortical white matter (forceps minor).2. Four distinct types of PSPs were recorded (at the resting potential) under normal physiological conditions; 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX)-sensitive excitatory postsynaptic potentials (EPSPs) were followed by bicuculline- or picrotoxin-sensitive depolarizing or hyperpolarizing inhibitory postsynaptic potentials (IPSPs), which were further followed by phaclofen-sensitive, long-lasting hyperpolarizing postsynaptic potentials (LPSPs). The average times-to-peak for the EPSP, depolarizing and hyperpolarizing IPSPs, and LPSP were 10, 22, 28, and 146 ms, respectively.3. In the presence of CNQX and bicuculline, high-intensity electrical stimulation elicited a longer lasting EPSP with a time-to-peak of 21 ms. The amplitude and duration of the EPSP decreased with membrane hyperpolarization and increased with membrane depolarization. The EPSP was reversibly abolished by D,L-2-amino-5-phosphonovaleric acid (D,L-APV).4. The bicuculline- or picrotoxin-sensitive depolarizing and hyperpolarizing IPSPs and the phaclofen-sensitive LPSP were markedly suppressed by CNQX, suggesting that glutamate (Glu) and/or aspartate nerve terminals project to GABAergic interneurons, and that the GABAergic interneurons are activated mainly by non-N-methyl-D-aspartate (non-NMDA) receptors.5. In the presence of picrotoxin, the average reversal potential for the compound EPSP was 0 mV, which was similar to that (-6 mV) for the Glu-induced depolarization. In a solution containing D,L-APV at low concentrations, the average reversal potentials for the depolarizing and hyperpolarizing IPSPs and for the early and late components of the gamma-aminobutyric acid (GABA)-induced responses were -62, -72, -70, and -61 mV, respectively. Thus the value for the depolarizing IPSP was similar to that for the late response to GABA, whereas the value for the hyperpolarizing IPSP was almost the same as that for the early response to GABA. The average reversal potential of -90 mV for the LPSP was similar to -93 mV for the baclofen-induced hyperpolarization and to -94 mV for the spike afterhyperpolarization.6. Application of phaclofen decreased the interspike interval of the spontaneous firing and reversed the increase in the interspike interval after subcortical stimulation. This result indicates that, even in a slice preparation, the anterior cingulate neurons are under tonic inhibitory control exerted by spontaneously active GABAergic interneurons.7. Application of bicuculline or picrotoxin at higher concentrations, or removal of extracellular Mg2+, led to the development of spontaneous and evoked epileptiform burst discharges. The discharge was reversibly blocked by Co2+, CNQX, D,L-APV, an organic Ca2+ antagonist, flunarizine, or a low Ca2+ and high Mg2+ medium.8. Application of Glu or NMDA produced a depolarization followed by a prolonged hyperpolarization. Quisqualate (Quis) had similar effects, but alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) or kainate had none. The post-Glu hyperpolarization was reversed in polarity at a membrane potential of -94 mV. Further analyses suggest that a small Ca2+ entry from NMDA receptor activation evokes Ca2+ release from intracellular stores, which then activates Ca2+-dependent K+ conductances.9. These results provide evidence that the anterior cingulate neurons are under strong inhibitory control exerted by GABAergic interneurons.