Jiang Li, Role Lorna W
Center for Neurobiology and Behavior, Columbia University College of Physicians & Surgeons, 630 West 168th Street, New York, NY 10032, USA.
J Neurophysiol. 2008 Apr;99(4):1988-99. doi: 10.1152/jn.00933.2007. Epub 2008 Feb 13.
The basolateral nucleus of the amygdala (BLA) receives cholinergic innervation from the basal forebrain and nicotine, via activation of neuronal nicotinic acetylcholine receptors (nAChRs), can improve performance in amygdala-based learning tasks. We tested the hypothesis that acute and prenatal nicotine exposure modulates cortico-amygdala synaptic transmission. We found that low-dose, single-trial exposures to nicotine can elicit lasting facilitation, the extent of which is dependent on the level of stimulation of the cortical inputs to the BLA. In addition, sustained facilitation is ablated by prenatal exposure to nicotine. This study examined synaptic transmission in 238 patch-clamp recordings from BLA neurons in acute slice from mouse brain. Pharmacological studies in wild-type and nAChR subunit knock-out mice reveal that activation of presynaptic alpha 7, containing (alpha 7*) and non-alpha 7* nAChRs, facilitates glutamatergic transmission in an activity-dependent manner. Without prior stimulation, application of nicotine elicits modest and transient facilitation of glutamatergic postsynaptic currents (PSCs) in about 40% of BLA neurons. With low-frequency stimulation of cortical inputs nicotine elicits robust facilitation of transmission at about 60% of cortico-BLA synapses and synaptic strength remains elevated at about 40% of these connections for >15 min after nicotine washout. Following paired-pulse stimulation nicotine elicits long-lasting facilitation of glutamatergic transmission at about 70% of cortico-BLA connections. Nicotine reduces the threshold for activation of long-term potentiation of cortico-BLA synapses evoked by patterned stimulation. Prenatal exposure to nicotine reduced subsequent modulatory responses to acute nicotine application.
杏仁核基底外侧核（BLA）接受来自基底前脑的胆碱能神经支配，尼古丁通过激活神经元烟碱型乙酰胆碱受体（nAChRs），可改善基于杏仁核的学习任务表现。我们检验了急性和产前尼古丁暴露会调节皮质-杏仁核突触传递这一假说。我们发现，低剂量单次尼古丁暴露可引发持久的易化作用，其程度取决于对BLA皮质输入的刺激水平。此外，产前尼古丁暴露会消除这种持续的易化作用。本研究在来自小鼠脑急性切片的BLA神经元的238次膜片钳记录中检测了突触传递。对野生型和nAChR亚基敲除小鼠的药理学研究表明，含α7的突触前α7和非α7 nAChRs的激活以活动依赖的方式促进谷氨酸能传递。在没有预先刺激的情况下，应用尼古丁可在约40%的BLA神经元中引发适度且短暂的谷氨酸能突触后电流（PSC）易化。在对皮质输入进行低频刺激时，尼古丁可在约60%的皮质-BLA突触处引发强大的传递易化，并且在尼古丁洗脱后>15分钟，约40%的这些连接的突触强度仍保持升高。在配对脉冲刺激后，尼古丁可在约70%的皮质-BLA连接中引发谷氨酸能传递的持久易化。尼古丁降低了由模式刺激诱发的皮质-BLA突触长时程增强的激活阈值。产前尼古丁暴露降低了随后对急性尼古丁应用的调节反应。
