Hasuo H, Akasu T
Department of Physiology, Kurume University School of Medicine, 67 Asahi-machi, 830-0011, Kurume, Japan.
Neuroscience. 2001;105(2):343-52. doi: 10.1016/s0306-4522(01)00195-6.
Long-term potentiation of the hippocampal-septal pathway was examined by intracellular recording techniques. High frequency stimulation (two 100-Hz 1-s trains with a 20-s interval between them) of the hippocampal CA3 area resulted in a transient depolarization in rat lateral septal nucleus neurons. High frequency stimulation was followed by a facilitation of fast and slow inhibitory postsynaptic potentials, lasting for more than 2 h, but not by a long-lasting increase in the excitatory postsynaptic potential in the normal solution. Long-term potentiation (>2 h) of the excitatory postsynaptic potential did not appear in 74% of neurons tested, even when the fast inhibitory postsynaptic potential was blocked by bicuculline (30 microM), a GABA(A) receptor antagonist. High frequency stimulation produced long-term potentiation of the excitatory postsynaptic potential in the Mg(2+)-free solution containing bicuculline. When the fast and slow inhibitory postsynaptic potentials were blocked by GABA(A) and GABA(B) receptor antagonists (bicuculline and CGP 55845A respectively), high frequency stimulation produced a large and sustained depolarization followed by long-term potentiation of the excitatory postsynaptic potential. However, the excitatory postsynaptic potential was not enhanced by administration of these drugs after termination of high frequency stimulation. Pretreatment with 2-amino-5-phosphonopentanoate, a NMDA receptor antagonist, resulted in loss of long-term potentiation in both sets of experiments. Paired-pulse stimulation of the hippocampal CA3 region with interstimulus intervals between 200 and 800 ms depressed the second excitatory postsynaptic potential in the presence of bicuculline. CGP 35348, a GABA(B) receptor antagonist, reversed the depression of excitatory postsynaptic potentials to facilitation. These data suggest that high frequency stimulation of hippocampal CA3 neurons enhances the efficacy of GABAergic inhibitory circuits which, in turn, depress the ability of lateral septal nucleus neurons to express long-term potentiation.
采用细胞内记录技术研究了海马-隔区通路的长时程增强。对海马CA3区进行高频刺激（两串100Hz、持续1秒的刺激，间隔20秒），导致大鼠外侧隔核神经元出现短暂去极化。高频刺激后，快、慢抑制性突触后电位增强，持续超过2小时，但在正常溶液中兴奋性突触后电位并未出现持久增加。在74%的受试神经元中，即使使用GABA(A)受体拮抗剂荷包牡丹碱（30μM）阻断快抑制性突触后电位，兴奋性突触后电位的长时程增强（>2小时）也未出现。在含荷包牡丹碱的无镁溶液中，高频刺激可产生兴奋性突触后电位的长时程增强。当快、慢抑制性突触后电位分别被GABA(A)和GABA(B)受体拮抗剂（荷包牡丹碱和CGP 55845A）阻断时，高频刺激会产生大幅且持续的去极化，随后兴奋性突触后电位出现长时程增强。然而，在高频刺激终止后给予这些药物，兴奋性突触后电位并未增强。用NMDA受体拮抗剂2-氨基-5-磷酸戊酸预处理，在两组实验中均导致长时程增强消失。在荷包牡丹碱存在的情况下，海马CA3区成对脉冲刺激，刺激间隔在200至800毫秒之间，会抑制第二个兴奋性突触后电位。GABA(B)受体拮抗剂CGP 35348可将兴奋性突触后电位的抑制作用逆转至易化作用。这些数据表明，海马CA3神经元的高频刺激增强了GABA能抑制回路的效能，进而抑制外侧隔核神经元表达长时程增强的能力。
