Aramakis V B, Metherate R
Department of Psychobiology, University of California, Irvine, California 92697-4550, USA.
J Neurosci. 1998 Oct 15;18(20):8485-95. doi: 10.1523/JNEUROSCI.18-20-08485.1998.
The neurotransmitters acetylcholine (ACh) and glutamate have been separately implicated in synaptic plasticity during development of sensory neocortex. Here we show that these neurotransmitters can, in fact, act synergistically via their actions at nicotinic ACh receptors (nAChRs) and NMDA receptors, respectively. To determine how activation of nAChRs modifies glutamatergic EPSPs, we made whole-cell recordings from visualized pyramidal neurons in slices of rat auditory cortex. Pulsed (pressure) ejection of nicotine onto apical dendrites selectively enhanced EPSPs mediated by NMDA receptors without affecting AMPA/kainate (AMPA/KA) receptor-mediated EPSPs. The enhancement occurred during a transient, postnatal period of heightened cholinergic function [neurons tested on postnatal day 8-16 (P8-16)], and not in the mature cortex (>P19). Three related findings indicated the mechanism of action: (1) The specific alpha7 nAChR antagonist methyllycaconitine citrate (MLA) blocked the effect of nicotine; (2) pulsed nicotine did not enhance postsynaptic depolarizations induced by iontophoretically applied NMDA; and (3) bath exposure to nicotine for several minutes produced apparent nAChR desensitization and precluded enhancement of EPSPs by pulsed nicotine. Together, the data suggest that nicotine acts at rapidly desensitizing, presynaptic alpha7 nAChRs to increase glutamate release onto postsynaptic NMDA receptors. The synergistic actions mediated by alpha7 nAChRs and NMDA receptors may contribute to experience-dependent synaptic plasticity in sensory neocortex during early postnatal life.
神经递质乙酰胆碱（ACh）和谷氨酸分别被认为与感觉新皮层发育过程中的突触可塑性有关。在此我们表明，事实上，这些神经递质可分别通过作用于烟碱型乙酰胆碱受体（nAChRs）和NMDA受体而协同发挥作用。为了确定nAChRs的激活如何改变谷氨酸能兴奋性突触后电位（EPSPs），我们在大鼠听觉皮层切片中对可视化的锥体神经元进行了全细胞记录。将尼古丁脉冲式（压力）喷射到顶端树突上可选择性增强由NMDA受体介导的EPSPs，而不影响由AMPA/红藻氨酸盐（AMPA/KA）受体介导的EPSPs。这种增强发生在胆碱能功能增强的短暂出生后时期[在出生后第8 - 16天（P8 - 16）测试的神经元]，而在成熟皮层（>P19）中则不会发生。三个相关发现表明了其作用机制：（1）特异性α7 nAChR拮抗剂甲基lycaconitine柠檬酸盐（MLA）可阻断尼古丁的作用；（2）脉冲式尼古丁不会增强离子电渗法施加NMDA所诱导的突触后去极化；（3）将尼古丁浴灌暴露几分钟会导致明显的nAChR脱敏，并阻止脉冲式尼古丁增强EPSPs。总之，数据表明尼古丁作用于快速脱敏的突触前α7 nAChRs，以增加谷氨酸释放到突触后NMDA受体上。由α7 nAChRs和NMDA受体介导的协同作用可能有助于出生后早期感觉新皮层中依赖经验的突触可塑性。
