生物谷報道：研究人員發(fā)現(xiàn)了身體用來減弱大腦腹側(cè)被蓋區(qū)中的突觸響應(yīng)的一個獨特方法，大腦的該區(qū)與愉快和上癮有關(guān),。這項基礎(chǔ)研究也許能幫助更好地了解毒品上癮。突觸是神經(jīng)系統(tǒng)中的連接,，它們在神經(jīng)細(xì)胞間建立聯(lián)系,，也涉及諸如學(xué)習(xí)和記憶等功能。在大腦的大多數(shù)區(qū)域中,，突觸的強(qiáng)度由AMPA受體(AMPARs)家族的谷氨酸受體數(shù)量控制,， AMPARs家族管理中樞神經(jīng)系統(tǒng)中的突觸傳遞。Manuel Mameli和國際同事用小鼠作試驗,，發(fā)現(xiàn)腹側(cè)被蓋區(qū)中的突觸突觸強(qiáng)度能被下調(diào),。這個下調(diào)不是大腦多數(shù)區(qū)域中常見的通過減少AMPARs 數(shù)量實現(xiàn)的，而是已有的AMPARs被新的取代,，新受體有不同的子單位使其變?nèi)?。研究人員還發(fā)現(xiàn)這個谷氨酸受體子單位是在該過程中由神經(jīng)細(xì)胞新產(chǎn)生出來的,。
原始出處:
Science 27 July 2007:
Vol. 317. no. 5837, pp. 530 - 533
DOI: 10.1126/science.1142365
Reports
Rapid Synthesis and Synaptic Insertion of GluR2 for mGluR-LTD in the Ventral Tegmental Area
Manuel Mameli,1 Bénédicte Balland,1 Rafael Luján,2 Christian Lüscher1,3*
The activation of metabotropic glutamate receptors (mGluRs) leads to long-term depression (mGluR-LTD) at many synapses of the brain. The induction of mGluR-LTD is well characterized, whereas the mechanisms underlying its expression remain largely elusive. mGluR-LTD in the ventral tegmental area (VTA) efficiently reverses cocaine-induced strengthening of excitatory inputs onto dopamine neurons. We show that mGluR-LTD is expressed by an exchange of GluR2-lacking AMPA receptors for GluR2-containing receptors with a lower single-channel conductance. The synaptic insertion of GluR2 depends on de novo protein synthesis via rapid messenger RNA translation of GluR2. Regulated synthesis of GluR2 in the VTA is therefore required to reverse cocaine-induced synaptic plasticity.
1 Department of Basic Neuroscience, Medical Faculty, University of Geneva, CH-1211 Geneva, Switzerland.
2 Department Ciencias Médicas, Facultad de Medicina–Centro Regional de Investigaciones Biomedicas, Universidad de Castilla–La Mancha, 02006 Albacete, Spain.
3 Clinic of Neurology, Department of Clinical Neuroscience, Geneva University Hospital, CH-1211 Geneva, Switzerland.
* To whom correspondence should be addressed. E-mail: [email protected]
