Alkondon M, Albuquerque E X
Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
J Neurophysiol. 2001 Dec;86(6):3043-55. doi: 10.1152/jn.2001.86.6.3043.
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.
海马体是边缘脑区，参与记忆的编码和提取，它具有由兴奋性主神经元和抑制性中间神经元组装而成的明确结构网络。由于GABA能中间神经元在锥体神经元和中间神经元上均形成突触，某些中间神经元上存在的烟碱型乙酰胆碱受体（nAChRs）的激活可能在海马回路中诱导抑制或去抑制。为了解nAChRs在控制海马体突触传递中的作用，我们评估了锥体神经元和CA1区各种中间神经元中nAChR调节的GABA能突触后电流（PSCs）的大小。使用全细胞膜片钳记录以及大鼠海马切片中神经元类型的事后鉴定，我们发现，通过乙酰胆碱（1 mM）或胆碱（10 mM）对nAChRs进行短暂（12秒）激活，可增强锥体神经元和CA1中间神经元中GABA能PSCs的频率。通过胆碱诱导的PSCs的净电荷评估，α7 nAChR介导的GABA能抑制大小在分子层中间神经元中最高，其次是锥体神经元和辐射层中间神经元。相反，通过乙酰胆碱和胆碱诱导的PSCs净电荷之差评估，α4β2 nAChR介导的GABA能抑制大小在锥体神经元中最高，其次是分子层和辐射层中间神经元。目前的结果表明，通过nAChRs的特定亚型传递的胆碱能信号通过在靶神经元中诱导不同程度的GABA能抑制来改变海马体中的突触功能。
