Pawelzik H, Hughes D I, Thomson A M
Department of Physiology, Royal Free and UCL Medical School, Rowland Hill Street, London NW3 2PF, UK.
J Physiol. 2003 Feb 1;546(Pt 3):701-16. doi: 10.1113/jphysiol.2002.035121.
To determine whether autaptic inhibition plays a functional role in the adult hippocampus, the action potential afterhyperpolarisations (spike AHPs) of CA1 interneurones were investigated in 25 basket, three bistratified and eight axo-axonic cells. The spike AHPs showed two minima in all regular-spiking (5), burst-firing (3) and in many fast-spiking cells (17:28). The fast component had a time-to-peak (TTP) of 1.2 +/- 0.5 ms, the slower TTP was very variable (range of 3.3-103 ms). The AHP width at half-amplitude (HW) was 12.5 +/- 5.7 ms in fast-spiking, 29.3 +/- 18 ms in regular-spiking and 99.7 +/- 42 ms in burst-firing cells. Axo-axonic cells never establish autapses, and the fast-spiking variety showed narrow (HW: 3.9 +/- 0.7 ms) spike AHPs with only one AHP minimum (TTP: 0.9 +/- 0.1 ms). When challenged with GABA(A) receptor modulators, spike AHPs in basket and bistratified cells were enhanced by zolpidem (HW by 18.4 +/- 6.2 % in 10:15 cells tested), diazepam (45.2 +/- 0.5 %, 6:7), etomidate (43.9 +/- 36 %, 6:8) and pentobarbitone sodium (41 %, 1:1), and were depressed by bicuculline (-41 +/- 5.7 %, 5:8) and picrotoxin (-54 %, 1:1), and the enhancement produced by zolpidem was reduced by flumazenil (-31 +/- 13 %, relative to the AHP HW during exposure to zolpidem, 3:4). Neuronal excitability was modulated in parallel. The spike AHPs of three axo-axonic cells tested showed no sensitivity to etomidate, pentobarbitone or diazepam. Interneurone-to-interneurone inhibitory postsynaptic potentials (IPSPs), studied with dual intracellular recordings, had time courses resembling those of the spike AHPs. The IPSP HW was 13.4 +/- 2.8 ms in fast-spiking (n = 16) and 28.7 +/- 5.8 ms in regular-spiking/burst-firing cells (n = 6), and the benzodiazepine1-selective modulator zolpidem strongly enhanced these IPSPs (45 +/- 28 %, n = 5). Interneurones with spike AHPs affected by the GABA(A) receptor ligands exhibited 3.8 +/- 1.9 close autaptic appositions. In three basket cells studied at the ultrastructural level 6 of 6, 1 of 2 and 1 of 2 close appositions were confirmed as autapses. Therefore, in the hippocampus autaptic connections contribute to spike AHPs in many interneurones. These autapses influence neuronal firing and responses to GABA(A) receptor ligands.
为了确定自突触抑制在成年海马体中是否发挥功能作用，我们在25个篮状细胞、3个双分层细胞和8个轴-轴突细胞中研究了CA1中间神经元的动作电位后超极化（峰电位AHP）。在所有规则放电（5个）、爆发式放电（3个）以及许多快速放电细胞（17个中的28个）中，峰电位AHP均显示出两个最小值。快速成分的峰值时间（TTP）为1.2±0.5毫秒，较慢成分的TTP变化很大（范围为3.3 - 103毫秒）。快速放电细胞的AHP半幅宽度（HW）为12.5±5.7毫秒，规则放电细胞为29.3±18毫秒，爆发式放电细胞为99.7±42毫秒。轴-轴突细胞从不形成自突触，快速放电类型的轴-轴突细胞显示出狭窄的（HW：3.9±0.7毫秒）峰电位AHP，且只有一个AHP最小值（TTP：0.9±0.1毫秒）。当用GABA(A)受体调节剂进行刺激时，篮状细胞和双分层细胞中的峰电位AHP在使用唑吡坦（在10个测试的15个细胞中HW增加18.4±6.2%）、地西泮（45.2±0.5%，6个中的7个）、依托咪酯（43.9±36%，6个中的8个）和戊巴比妥钠（41%，1个中的1个）时增强，在使用荷包牡丹碱（-41±5.7%，5个中的8个）和印防己毒素（-54%，1个中的1个）时降低，并且唑吡坦产生的增强作用被氟马西尼减弱（相对于暴露于唑吡坦期间的AHP HW降低31±13%，3个中的4个）。神经元兴奋性也随之平行调节。测试的3个轴-轴突细胞的峰电位AHP对依托咪酯、戊巴比妥或地西泮不敏感。用双细胞内记录研究的中间神经元到中间神经元的抑制性突触后电位（IPSP）的时间进程与峰电位AHP相似。快速放电细胞（n = 16）的IPSP HW为13.4±2.8毫秒，规则放电/爆发式放电细胞（n = 6）为28.7±5.8毫秒，苯二氮䓬1选择性调节剂唑吡坦强烈增强了这些IPSP（45±28%，n = 5）。其峰电位AHP受GABA(A)受体配体影响的中间神经元表现出3.8±1.9个紧密的自突触连接。在超微结构水平研究的3个篮状细胞中，6个中的6个、2个中的1个和2个中的1个紧密连接被确认为自突触。因此，在海马体中，自突触连接在许多中间神经元的峰电位AHP形成中起作用。这些自突触影响神经元的放电以及对GABA(A)受体配体的反应。
