Use-dependent shift from inhibitory to excitatory GABAA receptor action in SP-O interneurons in the rat hippocampal CA3 area
Use-dependent shift from inhibitory to excitatory GABAA receptor action in SP-O interneurons in the rat hippocampal CA3 area
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DOI：
10.1152/jn.00060.2003
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发表时间：
2003-09-01
影响因子：
2.5
通讯作者：
Taira, T
中科院分区：
文献类型：
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作者：
Lamsa, K;Taira, T
皮质抑制中间神经元决定了突触可塑性和各种认知功能所涉及的同步神经元振荡的速度。中间神经元抑制性突触后电位(IPSP)的超极化特性被认为是在β(15-30 Hz)和伽马(30-100 Hz)频率产生振荡的关键。锥体细胞层内的海马篮细胞和轴突细胞(S-PO)在局部神经元间网络的同步化和谷氨酸能主细胞放电的起搏中起着中心作用。兴奋性突触与中间神经元之间缺乏常规形式的可塑性，有利于它们作为稳定的神经元振荡器发挥作用。我们用粗面菌素穿孔和全细胞钳记录方法研究了在5-100赫兹电刺激和自发活动过程中，GABA(A)R在大鼠海马片CA3 SP-O中间神经元和CA3锥体细胞中的传递特性。我们发现，SP-O中间神经元上的GABA能突触在活动增强时可以很容易地将其模式从抑制性转换为兴奋性。这是基于GABA(A)逆转电位(EGABA-A)的去极化变化，这种变化在中间神经元中比在锥体细胞中要快得多，也更明显。我们还发现，神经元间功能的变化是频率依赖性的，在GABA能突触的20-40赫兹激活时最为显著。在40 Hz强直刺激(100个脉冲)后，中间神经元的GABA(A)反应保持去极化状态约45个S，促进GABA能网络的爆发。超极化的EGBA-A在刺激训练后恢复>；60 S。脑片上应用4-氨基吡啶(100um)可诱发类似的自发GABA能爆发。GABA(A)R向去极化IPSP的转变意味着弱酸性阴离子甲酸盐引起神经元间群体爆发，支持GABA能兴奋在爆发产生中的作用。GABA(A)Rs的正性变构调节剂戊巴比妥(100um)可增强GABA能电位的去极化和神经元间的同步性爆发，并可被印防己毒素(100um)阻断。有趣的是，GABA能爆发在15-40赫兹表现出短暂的(S)振荡，即使在SP-O中间神经元中只看到去极化的GABA(A)反应。神经元间网络的这种β-伽马节律性依赖于电紧张性耦合，并可被甘草酸(200mM)阻断缝隙连接而取消。这些结果表明，SP-O中间神经元中超极化IPSP的快速活动依赖于降解，从而为给定的中间神经元参与由GABA能突触同步的β-伽马振荡设定了时间限制。此外，它们还暗示，中间神经元提供的相互GABA能兴奋可能是神经元网络功能中不可或缺的一部分。我们认为，EGABA-A的使用依赖性变化可能代表了促进局部GABA能网络连贯和持续激活的中间神经元的一种短期可塑性。
Cortical inhibitory interneurons set the pace of synchronous neuronal oscillations implicated in synaptic plasticity and various cognitive functions. The hyperpolarizing nature of inhibitory postsynaptic potentials (IPSPs) in interneurons has been considered crucial for the generation of oscillations at beta (15 - 30 Hz) and gamma (30 - 100 Hz) frequency. Hippocampal basket cells and axo-axonic cells in stratum pyramidale-oriens (S-PO) play a central role in the synchronization of the local interneuronal network as well as in pacing of glutamatergic principal cell firing. A lack of conventional forms of plasticity in excitatory synapses onto interneurons facilitates their function as stable neuronal oscillators. We have used gramicidin-perforated and whole cell clamp recordings to study properties of GABA(A) R-mediated transmission in CA3 SP-O interneurons and in CA3 pyramidal cells in rat hippocampal slices during electrical 5- to 100-Hz stimulation and during spontaneous activity. We show that GABAergic synapses onto SP-O interneurons can easily switch their mode from inhibitory to excitatory during heightened activity. This is based on a depolarizing shift in the GABA(A) reversal potential (EGABA-A), which is much faster and more pronounced in interneurons than in pyramidal cells. We also found that the shift in interneuronal function was frequency dependent, being most prominent at 20- to 40-Hz activation of the GABAergic synapses. After 40-Hz tetanic stimulation (100 pulses), GABA(A) responses remained depolarizing for similar to 45 s in the interneurons, promoting bursting in the GABAergic network. Hyperpolarizing EGABA-A was restored > 60 s after the stimulus train. Similar but spontaneous GABAergic bursting was induced by application of 4-aminopyridine (100 muM) to slices. A shift to depolarizing IPSPs by the GABA(A)R permeant weak acid anion formate provoked interneuronal population bursting, supporting the role of GABAergic excitation in burst generation. Furthermore, depolarizing GABAergic potentials and synchronous interneuronal bursting were enhanced by pentobarbital ( 100 muM), a positive allosteric modulator of GABA(A)Rs, and were blocked by picrotoxin (100 muM). Intriguingly, GABAergic bursts displayed short ( < 1 s) oscillations at 15 - 40 Hz, even though only depolarizing GABA(A) responses were seen in the SP-O interneurons. This beta-gamma rhythmicity in the interneuron network was dependent on electrotonic coupling, and was abolished by blockade of gap junctions with carbenoxolone ( 200 mu M). Results here implicate the rapid activity-dependent degradation of hyperpolarizing IPSPs in SP-O interneurons in setting the temporal limits for a given interneuron to participate in beta-gamma oscillations synchronized by GABAergic synapses. Furthermore, they imply that mutual GABAergic excitation provided by interneurons may be an integral part in the function of neuronal networks. We suggest that the use-dependent change in EGABA-A could represent a form of short-term plasticity in interneurons promoting coherent and sustained activation of local GABAergic networks.