HIPPOCAMPAL CA1 LACUNOSUM-MOLECULARE INTERNEURONS - MODULATION OF MONOSYNAPTIC GABAERGIC IPSCS BY PRESYNAPTIC GABA(B) RECEPTORS
HIPPOCAMPAL CA1 LACUNOSUM-MOLECULARE INTERNEURONS - MODULATION OF MONOSYNAPTIC GABAERGIC IPSCS BY PRESYNAPTIC GABA(B) RECEPTORS
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DOI：
10.1152/jn.1995.74.5.2126
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发表时间：
1995-11-01
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：
KHAZIPOV, R;CONGAR, P;BENARI, Y
1. 采用全细胞膜片钳记录技术，对3- 4周龄大鼠海马CA1区的空洞层分子或辐射层边界附近（LM中间神经元）的单突触抑制性突触后电流（IPSCs）进行形态学和电生理学鉴定。在谷氨酸受体拮抗剂6-氰-7-硝基喹啉-2,3-二酮（CNQX, 20 μ M）和d -2-氨基-5-磷酸戊酸酯（APV, 50 μ M）存在下诱发的单突触IPSCs是双相的。γ -氨基丁酸-A （GABA(A)）受体拮抗剂bicuculline （20 μ M）阻断快速IPSC， GABA(B)受体拮抗剂CGP35348 （500 μ M）阻断慢速IPSC。电刺激可在齿状回的辐射层、取向层、空隙层和分子层等多个远端区域诱发单突触IPSCs，提示海马中存在广泛的抑制性中间神经元网络。在CA1中间神经元和锥体细胞的成对记录中，电刺激除齿状回分子层外，大多数远端区域都能诱发IPSC，仅在LM中间神经元中诱发IPSC。频繁（> - 0.1 Hz）的刺激抑制了诱导的IPSCs。在配对脉冲方案下，第二IPSC被抑制，并且在间隔100-200 ms时观察到最大抑制（40-50%）。GABA(B)受体激动剂巴氯芬（1 μ M）可降低诱导IPSC的振幅，抑制第二IPSC的成对脉冲。GABA(B)受体拮抗剂CGP35348 （0.5-1 mM）对离体ipsc的振幅无显著影响。然而，CGP35348减少但不能完全阻断成对脉冲抑制，这表明这种抑制部分是由于突触前GABA(B)受体的激活。对脉冲抑制取决于递质释放水平。通过将细胞外Ca2+浓度增加到4 mM，将细胞外Mg2+浓度降低到0.1 mM，增强GABA的突触释放，增强了抑制作用。通过将细胞外Mg2+浓度增加到7 mM来减少递质释放，可以减少IPSCs的成对脉冲抑制。在增强递质释放后，CGP35348降低配对脉冲抑制的效率较低，这表明高钙/低镁介质对抑制的增强优先是由于GABA(B)无关成分的增强。综上所述，在LM中间神经元中记录的单突触IPSCs与锥体细胞中记录的IPSCs具有相似的特征。递质释放水平与成对脉冲抑制程度之间的强相关性可能具有重要的生理后果，因为在具有高水平活动和高水平GABA释放的突触中，抑制作用很强，但抑郁更容易发展。
1. Whole cell patch-clamp recordings were employed to characterize monosynaptic inhibitory postsynaptic currents (IPSCs) in morphologically and electrophysiologically identified interneurons located in the stratum lacunosum moleculare, or near the border of the stratum radiatum (LM interneurons), in the CA1 region of hippocampal slices taken from 3- to 4-wk-old rats. Monosynaptic IPSCs, evoked in the presence of glutamate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 20 mu M) and D-2-amino-5-phosphopentanoate (APV; 50 mu M) were biphasic. The gamma-aminobutyric acid-A (GABA(A)) receptor antagonist, bicuculline (20 mu M), blocked the fast IPSC, and the slow IPSC was blocked by the GABA(B) receptor antagonist CGP35348 (500 mu M).2. Monosynaptic IPSCs were evoked by electrical stimulation in several distant regions including the stratum radiatum, the stratum oriens, the stratum lacunosum-moleculare, and the molecular layer of dentate gyrus, suggesting an extensive network of inhibitory interneurons in the hippocampus. In paired recordings of CA1 interneurons and pyramidal cells, IPSCs were evoked by electrical stimulation of most of these distal regions with the exception of the molecular layer of dentate gyrus, which evoked an IPSC only in LM interneurons.3. Frequent(>0.1 Hz) stimulation depressed the evoked IPSCs. With a paired-pulse protocol, the second IPSC was depressed and the maximal depression (40-50%) was observed with an interstimulus interval of 100-200 ms.4. The GABA(B) receptor agonist baclofen (1 mu M) reduced the amplitude of evoked IPSCs and the paired-pulse depression of the second IPSC. The GABA(B) receptor antagonist CGP35348 (0.5-1 mM) had no significant effect on the amplitude of isolated IPSCs. However, CGP35348 reduced but did not fully block paired-pulse depression, suggesting that this depression is partly due to the activation of presynaptic GABA(B) receptors.5. The paired-pulse depression depended on the level of transmitter release. Potentiation of synaptic release of GABA, by increasing the extracellular Ca2+ concentration to 4 mM and reducing the extracellular Mg2+ concentration to 0.1 mM, enhanced the depression. Reduction of transmitter release by increasing extracellular Mg2+ concentration to 7 mM diminished the paired-pulse depression of IPSCs. After potentiation of transmitter release, CGP35348 was less efficient in reducing the paired-pulse depression, suggesting that enhancement of depression by high-calcium/low-magnesium medium was preferentially due to the potentiation of a GABA(B)-independent component.6. In summary, monosynaptic IPSCs recorded in LM interneurons show similar features to those recorded in pyramidal cells. The strong correlation between the level of transmitter release and the degree of paired-pulse depression may have important physiological consequences, because in synapses with a high level of activity and a high level of GABA release, inhibition is powerful, but depression can develop more readily.