Kindling-induced long-lasting changes in synaptic transmission in the basolateral amygdala.
Kindling-induced long-lasting changes in synaptic transmission in the basolateral amygdala.
复制标题
点燃引起基底外侧杏仁核突触传递的持久变化。
DOI：
10.1152/jn.1992.67.2.443
复制
发表时间：
1992
影响因子：
2.5
通讯作者：
Shinnick-Gallagher,P
中科院分区：
文献类型：
--
作者：
Rainnie,DG;Asprodini,EK;Shinnick-Gallagher,P
1.正常和点燃动物杏仁基底外侧核(BLA)神经元的细胞内电流钳记录。用刺激终纹(ST)或杏仁外侧核(LA)诱发的突触后电位，研究兴奋性和抑制性氨基酸传递在点燃诱发癫痫样活动中的作用。用非N-甲基-D-天冬氨酸(Non-NMDA)拮抗剂6-氰基-7-硝基喹恶啉-2，3-二酮(CNQX)、NMDA拮抗剂DL-2-氨基-5-膦戊酸(APV)和GABA能受体亚型甲基荷包牡丹碱(BMI)分析谷氨酸和GABA受体亚型的贡献。2.对照神经元诱发的突触波形由兴奋性突触后电位、快抑制性突触后电位和慢抑制性突触后电位组成。刺激ST或LA通路可引起点燃动物对侧BLA神经元的爆发式放电反应。3.APV(50微米)可降低点燃动物BLA神经元的爆发放电反应，而CNQX(10微米)则可完全阻断点燃动物BLA神经元的爆发放电反应和荷包牡丹碱诱发的对照神经元爆发。4.点燃显著增加突触传递的慢和快成分(分别为S和f-EPSP)的幅值。此外，在点燃动物的脑片中，仅在动作电位产生的阈值以下激发EPSP所需的刺激强度明显较低。5.在点燃的神经元中，膜输入电阻和静息膜电位以及对去极化电流的反应所诱发的动作电位的数目没有明显变化。6.点燃导致ST和LA诱发的前馈GABA能突触传递和自发IPSP的通路特异性丢失。在相同的BLA神经元中，通过刺激LA直接抑制GABA不受点燃的影响。7.谷氨酸能传递的增强并不是由于解除抑制，因为在BMI和CNQX的存在下，点燃神经元的S-EPSP幅度仍然大于对照神经元。8.这些结果提供了证据，证明点燃后在BLA神经元中观察到的癫痫样活动是由于兴奋性NMDA型和非NMDA型受体介导的谷氨酸能传递的增加以及抑制性的γ-氨基丁酸(GABA)受体介导的传递的减少所致；兴奋性传递的增强不能用抑制的减少来解释。
1. Intracellular current-clamp recordings were obtained from neurons of the basolateral amygdala (BLA) in an in vitro slice preparation from control and kindled animals. Postsynaptic potentials, elicited by stimulation of the stria terminalis (ST) or lateral amygdaloid nucleus (LA), were used to investigate the role of excitatory and inhibitory amino acid transmission in kindling-induced epileptiform activity. The contributions of glutamatergic and GABAergic receptor subtypes were analyzed by use of the non-N-methyl-D-aspartate (non-NMDA) antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), the NMDA antagonist DL-2-amino-5-phosphonovaleric acid (APV), and the GABAA antagonist bicuculline methiodide (BMI). 2. The synaptic waveform evoked in control neurons consisted of an excitatory postsynaptic potential (EPSP), a fast inhibitory postsynaptic potential (f-IPSP), and a slow inhibitory postsynaptic potential (s-IPSP). Stimulation of the ST or LA pathways evoked a burst-firing response in BLA neurons contralateral from the site of stimulation of kindled animals. 3. APV (50 microM) reduced, but CNQX (10 microM) completely blocked, the burst-firing response in BLA neurons from kindled animals and bicuculline-induced bursting in control neurons. 4. Kindling significantly increased the amplitude of both the slow NMDA- and the fast non-NMDA-receptor-mediated components of synaptic transmission (s- and f-EPSPs, respectively). Furthermore, the stimulus intensities required to evoke EPSPs just subthreshold for action potential generation were significantly lower in slices from kindled animals. 5. In kindled neurons no significant change was observed in the membrane input resistance and resting membrane potential or in the number of action potentials elicited in response to depolarizating current injection. 6. Kindling resulted in a pathway-specific loss of ST- and LA-evoked feedforward GABAergic synaptic transmission and of spontaneous IPSPs. In the same BLA neurons, direct GABAergic inhibition via stimulation of the LA was not affected by kindling. 7. The enhanced glutamatergic transmission was not due to disinhibition, because, in the presence of BMI (and CNQX to prevent BMI-induced bursting), the s-EPSP amplitude was still greater in kindled than in control neurons. 8. These results provide evidence that the epileptiform activity observed in BLA neurons after kindling results from an increase in excitatory NMDA- and non-NMDA-receptor-mediated glutamatergic transmission and a decrease in inhibitory gamma-aminobutyric acid (GABA)-receptor-mediated transmission; the enhanced excitatory transmission cannot be accounted for by reduced inhibition.(ABSTRACT TRUNCATED AT 400 WORDS)