Zhu Ping Jun, Stewart Randall R, McIntosh J Michael, Weight Forrest F
Laboratory of Molecular and Cellular Neurobiology, NIH/NIAAA, 5625 Fishers Ln./Rm. TS-28, Bethesda, MD 20892-9411, USA.
J Neurophysiol. 2005 Nov;94(5):3081-91. doi: 10.1152/jn.00974.2004. Epub 2005 Jul 20.
The basolateral amygdala (BLA) is a critical component of the amygdaloid circuit, which is thought to be involved in fear conditioned responses. Using whole cell patch-clamp recording, we found that activation of nicotinic acetylcholine receptors (nAChRs) leads to an action potential-dependent increase in the frequency of spontaneous GABAergic currents in principal neurons in the BLA. These spontaneous GABAergic currents were abolished by a low-Ca2+/high-Mg2+ bathing solution, suggesting that they are spontaneous inhibitory postsynaptic currents (sIPSCs). Blockade of ionotropic glutamate receptors did not prevent this increased frequency of sIPSCs nor did blockade of alpha7 nAChRs. Among the nAChR agonists tested, cystisine was more effective at increasing the frequency of the sIPSCs than nicotine or 1,1-dimethyl-4-phenyl piperazinium iodide, consistent with a major contribution of beta4 nAChR subunits. The nicotinic antagonist, dihydro-beta-erythroidine, was less effective than d-tubocurarine in blocking the increased sIPSC frequency induced by ACh, suggesting that alpha4-containing nAChR subunits do not play a major role in the ACh-induced increased sIPSC frequency. Although alpha2/3/4/7 and beta2/4 nAChR subunits were found in the BLA by RT-PCR, the agonist and antagonist profiles suggest that the ACh-induced increase in sIPSC frequency involves predominantly alpha3beta4-containing nAChR subunits. Consistent with this, alpha-conotoxin-AuIB, a nAChR antagonist selective for the alpha3beta4 subunit combination, inhibited the ACh-induced increase in the frequency of sIPSCs. The observations suggest that nicotinic activation increases the frequency of sIPSCs in the BLA by acting mainly on alpha3beta4-containing nicotinic receptors on GABAergic neurons and may play an important role in the modulation of synaptic transmission in the amygdala.
基底外侧杏仁核（BLA）是杏仁核回路的关键组成部分，该回路被认为与恐惧条件反应有关。通过全细胞膜片钳记录，我们发现烟碱型乙酰胆碱受体（nAChRs）的激活导致BLA中主要神经元的自发性GABA能电流频率在动作电位依赖的情况下增加。这些自发性GABA能电流被低钙/高镁的灌流液所消除，表明它们是自发性抑制性突触后电流（sIPSCs）。离子型谷氨酸受体的阻断并不能阻止sIPSCs频率的这种增加，α7 nAChRs的阻断也不能。在所测试的nAChR激动剂中，半胱氨酸比尼古丁或1,1 - 二甲基 - 4 - 苯基哌嗪碘化物更有效地增加sIPSCs的频率，这与β4 nAChR亚基的主要作用一致。烟碱拮抗剂二氢 - β - 刺桐碱在阻断ACh诱导的sIPSC频率增加方面比d - 筒箭毒碱效果更差，表明含α4的nAChR亚基在ACh诱导的sIPSC频率增加中不发挥主要作用。尽管通过RT - PCR在BLA中发现了α2/3/4/7和β2/4 nAChR亚基，但激动剂和拮抗剂的作用模式表明，ACh诱导的sIPSC频率增加主要涉及含α3β4的nAChR亚基。与此一致的是，α - 芋螺毒素 - AuIB，一种对α3β4亚基组合具有选择性的nAChR拮抗剂，抑制了ACh诱导的sIPSCs频率增加。这些观察结果表明，烟碱激活主要通过作用于GABA能神经元上含α3β4的烟碱受体来增加BLA中sIPSCs的频率，并且可能在杏仁核突触传递的调节中发挥重要作用。
