کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6272381 | 1614772 | 2015 | 15 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
α6-Containing nicotinic acetylcholine receptors in midbrain dopamine neurons are poised to govern dopamine-mediated behaviors and synaptic plasticity
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کلمات کلیدی
HEPESα-Conotoxin MIILocomotorN-methyl-d-glucamineNMDGVTAAMPARAMPAnAChRNACEGTANACsSNC2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid - 2- [4- (2-hydroxyethyl) piperazin-1-yl] ethanesulfonic acidBAC - LACACh - آهethylene glycol tetraacetic acid - اتیلن گلیکول تتراستیک اسیدAcetylcholine - استیل کولینAddiction - اعتیاد substantia nigra pars compacta - توده سیاه پارس متراکمDopamine - دوپامینnon-transgenic - غیر ترانس ژنیکventral tegmental area - ناحیه تگمنتوم شکمیNicotine - نیکوتین Nucleus accumbens - هسته accumbensnucleus accumbens shell - هسته accumbens پوستهPlasticity - پلاستیکbacterial artificial chromosome - کروموزوم مصنوعی باکتریاییglutamate - گلوتاماتnicotinic acetylcholine receptor - گیرنده استیلکولین نیکوتین
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Acetylcholine (ACh) acts through nicotinic and muscarinic ACh receptors in the ventral midbrain and striatal areas to influence dopamine (DA) transmission. This cholinergic control of DA transmission is important for processes such as attention and motivated behavior, and is manipulated by nicotine in tobacco products. Identifying and characterizing the key ACh receptors involved in cholinergic control of DA transmission could lead to small molecule therapeutics for treating disorders involving attention, addiction, Parkinson's disease, and schizophrenia. α6-Containing nicotinic acetylcholine receptors (nAChRs) are highly and specifically expressed in midbrain DA neurons, making them an attractive drug target. Here, we used genetic, pharmacological, behavioral, and biophysical approaches to study this nAChR subtype. For many experiments, we used mice expressing mutant α6 nAChRs (“α6L9S” mice) that increase the sensitivity of these receptors to agonists such as ACh and nicotine. Taking advantage of a simple behavioral phenotype exhibited by α6L9S mice, we compared the ability of full versus partial α6â nAChR agonists to activate α6â nAChRs in vivo. Using local infusions of both agonists and antagonists into the brain, we demonstrate that neurons and nAChRs in the midbrain are sufficient to account for this behavioral response. To complement these behavioral studies, we studied the ability of in vivo α6â nAChR activation to support plasticity changes in midbrain DA neurons that are relevant to behavioral sensitization and addiction. By coupling local infusion of drugs and brain slice patch-clamp electrophysiology, we show that activating α6â nAChRs in midbrain DA areas is sufficient to enhance glutamatergic transmission in ventral tegmental area (VTA) DA neurons. Together, these results from in vivo studies strongly suggest that α6â nAChRs expressed by VTA DA neurons are positioned to strongly influence both DA-mediated behaviors and the induction of synaptic plasticity by nicotine.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience - Volume 304, 24 September 2015, Pages 161-175
Journal: Neuroscience - Volume 304, 24 September 2015, Pages 161-175
نویسندگان
J.N. Berry, S.E. Engle, J.M. McIntosh, R.M. Drenan,