Activation of nicotinic acetylcholine receptors increases the frequency of spontaneous GABAergic IPSCs in rat basolateral amygdala neurons.
Activation of nicotinic acetylcholine receptors increases the frequency of spontaneous GABAergic IPSCs in rat basolateral amygdala neurons.
复制标题
烟碱乙酰胆碱受体的激活增加了大鼠基底外侧杏仁核神经元中自发 GABA 能 IPSC 的频率。
DOI：
10.1152/jn.00974.2004
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发表时间：
2005
影响因子：
2.5
通讯作者：
Weight,ForrestF
中科院分区：
文献类型：
--
作者：
Zhu,PingJun;Stewart,RandallR;McIntosh,JMichael;Weight,ForrestF
杏仁基底外侧核(BLA)是杏仁核环路的重要组成部分，被认为参与恐惧条件性反应。在全细胞膜片钳记录中，我们发现烟碱型乙酰胆碱受体(NAChRs)的激活导致BLA主神经元自发GABA能电流频率的动作电位依赖性增加。这些自发的GABA能电流被低钙/高镁溶液所消除，表明它们是自发的抑制性突触后电流。阻断离子型谷氨酸受体不能阻止sIPSCs频率的增加，也不能阻断α7nAChRs。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-苯基哌嗪碘更有效地增加了sIPSCs的频率，这与β4nAChR亚基的主要贡献一致。烟碱拮抗剂二氢β-赤霉胺在阻断ACh诱导的sIPSC频率增加方面不如d-tubocurarine有效，提示α-4亚基在ACh诱导的sIPSC频率增加中不起主要作用。虽然逆转录聚合酶链式反应在血乳酸中发现了α2/3/4/7和β2/4nAChR亚基，但激动剂和拮抗剂图谱表明，ACh诱导的sIPSC频率的增加主要涉及含有α3β4的nAChR亚基。与此相一致的是，α-芋螺毒素-AuIB，一种选择性α-3-β-4亚单位组合的nAChR拮抗剂，抑制了ACh诱导的sIPSCs频率的增加。上述结果提示，尼古丁激活主要通过作用于GABA能神经元上含α-3、β-4的尼古丁受体而增加大鼠大脑白质内sIPSCs的频率，并可能在杏仁核突触传递的调节中发挥重要作用。
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 α7nAChRs. 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 β4nAChR subunits. The nicotinic antagonist, dihydro-β-erythroidine, was less effective than d-tubocurarine in blocking the increased sIPSC frequency induced by ACh, suggesting that α4-containing nAChR subunits do not play a major role in the ACh-induced increased sIPSC frequency. Although α2/3/4/7and β2/4nAChR 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 α3β4-containing nAChR subunits. Consistent with this, α-conotoxin-AuIB, a nAChR antagonist selective for the α3β4subunit 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 α3β4-containing nicotinic receptors on GABAergic neurons and may play an important role in the modulation of synaptic transmission in the amygdala.