Nicotinic acetylcholine receptors at glutamate synapses facilitate long-term depression or potentiation
Nicotinic acetylcholine receptors at glutamate synapses facilitate long-term depression or potentiation
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DOI：
10.1523/jneurosci.0542-05.2005
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发表时间：
2005-06-29
影响因子：
5.3
通讯作者：
Dani, JA
中科院分区：
文献类型：
--
作者：
Ge, SY;Dani, JA
海马体是学习和记忆的中心，接受丰富的胆碱能神经支配，并丰富表达烟碱型乙酰胆碱受体(NAChRs)。作用于海马体的尼古丁机制影响注意力、学习和记忆。在阿尔茨海默氏症期间，海马区的nAChRs和胆碱能神经支配功能下降。利用小鼠海马片，我们研究了nAChR在Schaffer侧支突触对CA1锥体神经元的影响的潜在多样性。当在这些兴奋性突触局部激发nAChR电流时，根据nAChR介导的兴奋和轻微电刺激之间的关系，可能会有不同的结果。当轻度突触前刺激与nAChR诱发的动作电位重合或先于nAChR诱发的动作电位1-5时，即可诱发长时程增强。然而，如果在电刺激前nAChR诱发的动作电位下降到1 S以内，则会导致长期的抑制。在这些时间框架之外，nAChR活性和刺激的不匹配导致了短期增强。结果表明，nAChRs可能对海马区的兴奋性事件有不同程度的影响。正在进行的nAChR活动可能调节谷氨酸传递的影响，并改变各种形式突触可塑性的概率。贯穿海马区的胆碱能纤维的精细网络形成了与锥体细胞、颗粒细胞和中间神经元的突触接触，确保了整个海马复合体中尼古丁机制的持续调节影响。在阿尔茨海默氏症等退行性疾病中，这些事件的中断可能会导致与尼古丁胆碱能功能下降相关的缺陷。
The hippocampus is a center for learning and memory that receives abundant cholinergic innervation and richly expresses nicotinic acetylcholine receptors (nAChRs). Nicotinic mechanisms acting on the hippocampus influence attention, learning, and memory. During Alzheimer's dementia, nAChRs and cholinergic innervation decline in the hippocampus. Using mouse hippocampal slices, we examined the potential diversity of nAChR influences at the Schaffer collateral synapse onto CA1 pyramidal neurons. When nAChR currents were elicited locally at those excitatory synapses, various outcomes were possible depending on the relationship between the nAChR- mediated excitation and mild electrical stimulation. When mild presynaptic stimulation coincided with or preceded nAChR- induced action potentials by 1-5 s, then long-term potentiation was induced. However, if the nAChR- induced action potentials fell within 1 s before the electrical stimulation, then long-term depression resulted. Outside of these time frames, the mismatch of nAChR activity and stimulation led to short-term potentiation. The results indicate that nAChRs may have various influences over excitatory events in the hippocampus. Ongoing nAChR activity likely modulates the impact of glutamate transmission and alters the probabilities for various forms of synaptic plasticity. The fine network of cholinergic fibers running through the hippocampus forms synaptic contacts onto pyramidal cells, granule cells, and interneurons, ensuring continual modulatory influence by nicotinic mechanisms throughout the hippocampal complex. Disruption of events such as those described here may contribute to the deficits associated with the decline of nicotinic cholinergic functions during degenerative diseases such as Alzheimer's dementia.