Nicotinic acetylcholine receptor alpha7 and alpha4beta2 subtypes differentially control GABAergic input to CA1 neurons in rat hippocampus.

Nicotinic acetylcholine receptor alpha7 and alpha4beta2 subtypes differentially control GABAergic input to CA1 neurons in rat hippocampus.
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发表时间:
2001
影响因子:
2.5
通讯作者:
M. Alkondon;E. Albuquerque
M. Alkondon;E. Albuquerque
中科院分区:
医学3区
文献类型:
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作者:
M. Alkondon;E. Albuquerque

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海马是参与记忆编码和提取的边缘脑区,具有由兴奋性主神经元和抑制性中间神经元组装的明确的结构网络。由于GABA能中间神经元在锥体神经元和中间神经元上形成突触,因此存在于某些中间神经元上的烟碱乙酰胆碱受体(nAChR)的激活可以诱导海马回路中的抑制或去抑制。为了了解nAChR在控制海马突触传递中的作用,我们评估了锥体神经元和CA 1区各种中间神经元中nAChR调制的GABA能突触后电流(PSC)的大小。使用全细胞膜片钳记录和事后鉴定大鼠海马脑片中的神经元类型,我们表明,短暂的(12-S)乙酰胆碱(1 mM)或胆碱(10 mM)激活乙酰胆碱受体增强GABA能PSC的频率在锥体神经元和CA 1中间神经元。通过胆碱诱导PSC的净电荷评估,α 7 nAChR介导的GABA能抑制的幅度在分子陷窝层中间神经元中最高,其次是锥体神经元和S。放射状中间神经元与此相反,α 4 β 2 nAChR介导的GABA能抑制的幅度,如由乙酰胆碱和胆碱诱导的PSC的净电荷之间的差异所评估的,在锥体神经元中最高,其次是s。lacunosum moleculare和S.放射状中间神经元目前的结果表明,胆碱能线索通过特定亚型的nAChRs通过诱导不同程度的GABA能抑制靶神经元中修改海马中的突触功能。
The hippocampus, a limbic brain region involved in the encoding and retrieval of memory, has a well-defined structural network assembled from excitatory principal neurons and inhibitory interneurons. Because the GABAergic interneurons form synapses onto both pyramidal neurons and interneurons, the activation of nicotinic acetylcholine receptors (nAChRs) present on certain interneurons could induce either inhibition or disinhibition in the hippocampal circuitry. To understand the role of nAChRs in controlling synaptic transmission in the hippocampus, we evaluated the magnitude of nAChR-modulated GABAergic postsynaptic currents (PSCs) in pyramidal neurons and various interneurons of the CA1 region. Using whole cell patch-clamp recording and post hoc identification of neuronal types in rat hippocampal slices, we show that brief (12-s) nAChR activation by ACh (1 mM) or choline (10 mM) enhances the frequency of GABAergic PSCs in both pyramidal neurons and CA1 interneurons. The magnitude of alpha7 nAChR-mediated GABAergic inhibition, as assessed by the net charge of choline-induced PSCs, was highest in stratum lacunosum moleculare interneurons followed by pyramidal neurons and s. radiatum interneurons. In contrast, the magnitude of alpha4beta2 nAChR-mediated GABAergic inhibition, as assessed by the difference between the net charge of PSCs induced by ACh and choline, was highest in pyramidal neurons followed by s. lacunosum moleculare and s. radiatum interneurons. The present results suggest that cholinergic cues transmitted via specific subtypes of nAChRs modify the synaptic function in the hippocampus by inducing a differential degree of GABAergic inhibition in the target neurons.