Barazangi N, Role L W
The Center for Neurobiology and Behavior, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
J Neurophysiol. 2001 Jul;86(1):463-74. doi: 10.1152/jn.2001.86.1.463.
Presynaptic nicotinic acetylcholine receptors (nAChRs) are thought to mediate some of the cognitive and behavioral effects of nicotine. The olfactory projection to the amygdala, and intra-amygdaloid projections, are limbic relays involved in behavioral reinforcement, a property influenced by nicotine. Co-cultures consisting of murine olfactory bulb (OB) explants and dispersed amygdala neurons were developed to reconstruct this pathway in vitro. Whole cell patch-clamp recordings were obtained from amygdala neurons contacted by OB explant neurites, and spontaneous and evoked synaptic currents were characterized. The majority of the 108 innervated amygdala neurons exhibited glutamatergic spontaneous postsynaptic currents (PSCs), 20% exhibited GABAergic spontaneous PSCs, and 17% exhibited both. Direct extracellular stimulation of OB explants elicited glutamatergic synaptic currents in amygdala neurons. Antibodies to nAChR subunits co-localized with an antibody to synapsin I, a presynaptic marker, along OB explant processes, consistent with the targeting of nAChR protein to presynaptic sites of the mitral cell projections. Hence, we examined the role of presynaptic nAChRs in modulating synaptic transmission in the OB-amygdala co-cultures. Focal application of 500 nM to 1 microM nicotine for 5-60 s markedly increased the frequency of spontaneous PSCs, without a change in the amplitude, in 39% of neurons that exhibited glutamatergic spontaneous PSCs (average peak fold increase = 125.2 +/- 33.3). Nicotine also enhanced evoked glutamatergic currents elicited by direct stimulation of OB explant fibers. Nicotine increased the frequency of spontaneous PSCs, without a change in the amplitude, in 35% of neurons that exhibited GABAergic spontaneous PSCs (average peak fold increase = 63.9 +/- 34.3). Thus activation of presynaptic nAChRs can modulate glutamatergic as well as GABAergic synaptic transmission in the amygdala. These results suggest that behaviors mediated by olfactory projections may be modulated by presynaptic nAChRs in the amygdala, where integration of olfactory and pheromonal input is thought to occur.
突触前烟碱型乙酰胆碱受体(nAChRs)被认为介导了尼古丁的一些认知和行为效应。嗅觉向杏仁核的投射以及杏仁核内的投射是参与行为强化的边缘系统中继站,而行为强化这一特性会受到尼古丁的影响。我们构建了由小鼠嗅球(OB)外植体和分散的杏仁核神经元组成的共培养体系,以便在体外重建这一通路。从与OB外植体神经突接触的杏仁核神经元中进行全细胞膜片钳记录,并对自发和诱发的突触电流进行特征描述。在108个有神经支配的杏仁核神经元中,大多数表现出谷氨酸能自发突触后电流(PSCs),20%表现出γ-氨基丁酸能自发PSCs,17%同时表现出这两种。对OB外植体进行直接细胞外刺激可在杏仁核神经元中诱发谷氨酸能突触电流。nAChR亚基的抗体与突触素I(一种突触前标记物)的抗体沿OB外植体突起共定位,这与nAChR蛋白靶向二尖瓣细胞投射的突触前位点一致。因此,我们研究了突触前nAChRs在调节OB-杏仁核共培养体系中突触传递的作用。在表现出谷氨酸能自发PSCs的39%的神经元中,局部施加500 nM至1 μM尼古丁5至60秒可显著增加自发PSCs的频率,而幅度不变(平均峰值增加倍数 = 125.2 ± 33.3)。尼古丁还增强了直接刺激OB外植体纤维诱发的谷氨酸能电流。在表现出γ-氨基丁酸能自发PSCs的35%的神经元中,尼古丁增加了自发PSCs的频率,而幅度不变(平均峰值增加倍数 = 63.9 ± 34.3)。因此,突触前nAChRs的激活可调节杏仁核中的谷氨酸能以及γ-氨基丁酸能突触传递。这些结果表明,由嗅觉投射介导的行为可能受到杏仁核中突触前nAChRs的调节,而嗅觉和信息素输入的整合被认为发生在杏仁核中。