Blocking GABA(A) inhibition reveals AMPA- and NMDA-receptor-mediated polysynaptic responses in the CA1 region of the rat hippocampus
Blocking GABA(A) inhibition reveals AMPA- and NMDA-receptor-mediated polysynaptic responses in the CA1 region of the rat hippocampus
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DOI：
10.1152/jn.1997.77.4.2071
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发表时间：
1997-04-01
影响因子：
2.5
通讯作者：
BenAri, Y
中科院分区：
文献类型：
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作者：
Crepel, V;Khazipov, R;BenAri, Y
阻断GABA(A)抑制揭示了大鼠海马CA1区AMPA-和nmda受体介导的多突触反应。中国生物医学工程学报，32(2):391 - 398。我们研究了在Wistar成年大鼠海马分离CA1区引起多突触反应所需的条件。实验采用细胞外和全细胞记录技术。在双球茎碱（10 μ M）、6-氰-7-硝基喹啉-2-3-二酮（10 μ M）、甘氨酸（10 μ M）和低浓度Mg2+ (0.3 mM)存在的情况下，电刺激Schaffer侧枝/连接通路可诱发CA1区辐射层n -甲基-d -天冬氨酸（NMDA） 1受体介导的梯度晚场电位。这些反应是通过多突触连接产生的，因为它们的潜伏期与刺激强度呈强烈的反比变化，并且它们被高浓度的二价阳离子（7 mM Ca2+）所消除。这些反应可能是由CA1锥体细胞轴突的局部侧支驱动的，因为在东方层局部应用河河毒素（30 μ M）强烈减少了晚期突触成分，而对CA1锥体细胞的反向刺激可引起多突触反应。电流源密度分析表明，多突触反应发生在CA1锥体细胞顶端树突近端（辐射层锥体细胞层下方50 ~ 150 μ m）。在Mg2+生理浓度（1.3 mM）下，药理学分离的nmda受体介导的多突触反应被消除。在对照人工脑脊液（生理浓度为Mg2+）中，双球茎碱（10 μ M）产生了分级多突触反应。在这些条件下，这种反应是由α -氨基-3-羟基-5-甲基-4-异恶唑丙酸(AMPA)/NMDA受体介导的。在d -2-氨基-5-磷酸戊酸（50 μ M）存在下，AMPA受体可以介导多突触反应，尽管效率较低。总之，γ -氨基丁酸-a抑制的抑制揭示了孤立CA1区域中谷氨酸受体介导的网络驱动事件。这些多突触反应是由AMPA和/或NMDA受体介导的，这取决于药理学条件和使用的Mg2+的外部浓度。我们认为这些反应是由CA1锥体细胞的局部复发侧枝驱动的。
Blocking GABA(A) inhibition reveals AMPA- and NMDA-receptor-mediated polysynaptic responses in the CA1 region of the rat hippocampus. J. Neurophysiol. 77: 2071-2082, 1997. We have investigated the conditions required to evoke polysynaptic responses in the isolated CA1 region of hippocampal slices from Wistar adult rats. Experiments were performed with extracellular and whole cell recording techniques. In the presence of bicuculline (10 mu M), 6-cyano-7-nitroquinoxaline-2-3-dione (10 mu M), glycine (10 mu M), and a low external concentration of Mg2+ (0.3 mM), electrical stimulation of the Schaffer collaterals/commissural pathway evoked graded N-methyl-D-aspartate (NMDA) 1-receptor-mediated late field potentials in the stratum radiatum of the CA1 region. These responses were generated via polysynaptic connections because their latency varied strongly and inversely with the stimulation intensity and they were abolished by a high concentration of divalent cations (7 mM Ca2+). These responses likely were driven by local collateral branches of CA1 pyramidal cell axons because focal application of tetrodotoxin (30 mu M) in the stratum oriens strongly reduced the late synaptic component and antidromic stimulation of CA1 pyramidal cells could evoke the polysynaptic response. Current-source density analysis suggested that the polysynaptic response was generated along the proximal part of the apical dendrites of CA1 pyramidal cells (50-150 mu m below the pyramidal cell layer in the stratum radiatum). In physiological concentration of Mg2+ (1.3 mM), the pharmacologically isolated NMDA-receptor-mediated polysynaptic response was abolished. In control artificial cerebrospinal fluid (with physiological concentration of Mg2+), bicuculline (10 mu M) generated a graded polysynaptic response. Under these conditions, this response was mediated both by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/NMDA receptors. In the presence of D-2-amino-5-phosphonovalerate (50 mu M), the polysynaptic response could be mediated by AMPA receptors, although less efficiently. In conclusion, suppression of gamma-aminobutyric acid-A inhibition reveals glutamate receptor-mediated network-driven events in the isolated CA1 region. These polysynaptic responses are mediated by AMPA and/or NMDA receptors depending on the pharmacological conditions and the external concentration of Mg2+ used. We suggest that these responses are driven by local recurrent collaterals of CA1 pyramidal cells.