生物谷报道：研究人员发现了身体用来减弱大脑腹侧被盖区中的突触响应的一个独特方法，大脑的该区与愉快和上瘾有关。这项基础研究也许能帮助更好地了解毒品上瘾。突触是神经系统中的连接，它们在神经细胞间建立联系，也涉及诸如学习和记忆等功能。在大脑的大多数区域中，突触的强度由AMPA受体(AMPARs)家族的谷氨酸受体数量控制， AMPARs家族管理中枢神经系统中的突触传递。Manuel Mameli和国际同事用小鼠作试验，发现腹侧被盖区中的突触突触强度能被下调。这个下调不是大脑多数区域中常见的通过减少AMPARs 数量实现的，而是已有的AMPARs被新的取代，新受体有不同的子单位使其变弱。研究人员还发现这个谷氨酸受体子单位是在该过程中由神经细胞新产生出来的。
原始出处:
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: Christian.Luscher@medecine.unige.ch
