Cholinergic modulation of appetite-related synapses in mouse lateral hypothalamic slice
Cholinergic modulation of appetite-related synapses in mouse lateral hypothalamic slice
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DOI：
10.1523/jneurosci.3638-05.2005
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发表时间：
2005-11-30
影响因子：
5.3
通讯作者：
Role, LW
中科院分区：
文献类型：
--
作者：
Jo, YH;Wiedl, D;Role, LW
服用尼古丁会降低食欲，改变进食模式；戒烟的一个主要障碍是过量吸烟和由此导致的体重增加。我们在此证明，涉及黑色素浓缩激素（MCH）神经元的外侧下丘脑（LH）回路受到胆碱能调节，这可能与尼古丁对食欲控制的影响有关。通过对囊泡乙酰胆碱（ACh）转运体（VAT）以及MCH和囊泡GABA转运体（vGABAT）抗体的免疫染色检查，证实了小鼠黄体周围LH区域的胆碱能输入。vacht阳性神经元与LH相邻，整个皮质周围区域检测到vacht阳性投影。MCH阳性树突似乎布满了vgabat阳性接触点，这与通过位置、形态、电生理特征和MCH表达识别的LH/MCH神经元的gaba能输入记录一致。突触前烟碱乙酰胆碱受体（nAChRs）的激活增强gaba能传递。gaba能通过(1)直接使用尼古丁，(2)增加局部ACh浓度，(3)刺激胆碱能投射增强传递。基于药理学研究和野生型与α 7 nAChR亚基突变小鼠的比较，我们提出α 7*-nAChR是调节LH中gaba能输入所必需的。产前暴露于尼古丁会引起产后幼崽LH中gaba能传递的持续升高。此外，产前尼古丁暴露的幼崽对LH的gaba能输入对随后的尼古丁挑战不敏感。我们的研究支持尼古丁给药或升高的胆碱能张力通过激活突触前α 7*- nachr增强对皮层周围LH/MCH神经元的抑制的假设。
Nicotine administration reduces appetite and alters feeding patterns; a major deterrent to smoking cessation is hyperphagia and resultant weight gain. We demonstrate here that lateral hypothalamic (LH) circuits involving melanin- concentrating hormone (MCH) neurons are subject to cholinergic modulation that may be related to the effects of nicotine on appetite control. Cholinergic input to the perifornical LH area of the mouse is confirmed by examination of immunostaining for vesicular acetylcholine (ACh) transporter (VAT) in conjunction with antibodies to MCH and the vesicular GABA transporter (vGABAT). vAChT-positive neurons border the LH, and VAT-positive projections are detected throughout the perifornical area. MCH-positive dendrites appear studded with vGABAT-positive contacts, consistent with recordings of GABAergic inputs to LH/MCH neurons identified by their location, morphology, electrophysiological profile, and MCH expression. Activation of presynaptic nicotinic ACh receptors (nAChRs) enhances GABAergic transmission. GABAergic transmission is potentiated by (1) direct nicotine application, (2) increasing local ACh concentration, and (3) stimulation of cholinergic projections. Based on pharmacological studies and comparisons of wild-type versus alpha 7 nAChR subunit mutant mice, we propose that alpha 7*-nAChRs are required for the modulation of GABAergic inputs in LH. Prenatal exposure to nicotine elicits a persistent elevation of GABAergic transmission in the LH of postnatal pups. Furthermore, GABAergic inputs to LH of prenatal nicotine- exposed pups are insensitive to subsequent nicotine challenge. Our studies support the hypothesis that nicotine administration or elevated cholinergic tone enhance inhibition of perifonical LH/MCH neurons via activation of presynaptic alpha 7*-nAChRs.