Radcliffe K A, Dani J A
Division of Neuroscience, Baylor College of Medicine, Houston, Texas 77030-3498, USA.
J Neurosci. 1998 Sep 15;18(18):7075-83. doi: 10.1523/JNEUROSCI.18-18-07075.1998.
Synaptic modulation and long-term synaptic changes are thought to be the cellular correlates for learning and memory (Madison et al., 1991; Aiba et al., 1994, Goda and Stevens, 1996). The hippocampus is a center for learning and memory that receives abundant cholinergic innervation and has a high density of nicotinic acetylcholine receptors (nAChRs) (Wada et al., 1989; Woolf, 1991). We report that stro ng, brief stimulation of nAChRs enhanced hippocampal glutamatergic synaptic transmission on two independent time scales and altered the relationship between consecutively evoked synaptic currents. The nicotinic synaptic enhancement required extracellular calcium and was produced by the activation of presynaptic alpha7-containing nAChRs. Although one form of glutamatergic enhancement lasted only for seconds, another form lasted for minutes after the nicotinic stimulation had ceased and the nicotinic agonist had been washed away. The synaptic enhancement lasting minutes suggests that nAChR activity can initiate calcium-dependent mechanisms that are known to induce glutamatergic synaptic plasticity. The results with evoked synaptic currents showed that nAChR activity can alter the relationship between the incoming presynaptic activity and outgoing postsynaptic signaling along glutamatergic fibers. Thus, the same information arriving along the same glutamatergic afferents will be processed differently when properly timed nicotinic activity converges onto the glutamatergic presynaptic terminals. Influencing information processing at glutamatergic synapses may be one way in which nicotinic cholinergic activity influences cognitive processes. Disruption of these nicotinic cholinergic mechanisms may contribute to the deficits associated with the degeneration of cholinergic functions during Alzheimer's disease.
突触调制和长期突触变化被认为是学习和记忆的细胞关联因素（麦迪逊等人，1991年；艾巴等人，1994年；戈达和史蒂文斯，1996年）。海马体是学习和记忆的中心，接受丰富的胆碱能神经支配，并且具有高密度的烟碱型乙酰胆碱受体（nAChRs）（和田等人，1989年；伍尔夫，1991年）。我们报告，对nAChRs进行强烈、短暂的刺激可在两个独立的时间尺度上增强海马体谷氨酸能突触传递，并改变连续诱发的突触电流之间的关系。烟碱型突触增强需要细胞外钙，并且是由含α7的突触前nAChRs的激活产生的。虽然一种形式的谷氨酸能增强仅持续数秒，但另一种形式在烟碱型刺激停止且烟碱型激动剂被洗脱后仍持续数分钟。持续数分钟的突触增强表明nAChR活性可以启动已知能诱导谷氨酸能突触可塑性的钙依赖性机制。诱发突触电流的结果表明，nAChR活性可以改变沿谷氨酸能纤维传入的突触前活动与传出的突触后信号之间的关系。因此，当适时的烟碱型活动汇聚到谷氨酸能突触前终末时，沿相同谷氨酸能传入纤维到达的相同信息将被不同地处理。影响谷氨酸能突触处的信息处理可能是烟碱型胆碱能活性影响认知过程的一种方式。这些烟碱型胆碱能机制的破坏可能导致与阿尔茨海默病期间胆碱能功能退化相关的缺陷。
