Ganea Dan A, Dines Monica, Basu Sreetama, Lamprecht Raphael
Sagol Department of Neurobiology, Faculty of Natural Sciences, University of Haifa, Haifa, Israel.
Neuropsychopharmacology. 2015 Nov;40(12):2727-35. doi: 10.1038/npp.2015.121. Epub 2015 Apr 27.
The membrane proximal region (MPR) of AMPA receptor (AMPAR) is needed for receptor trafficking and synaptic plasticity. However, its roles in long-term memory formation are not known. To assess the possible roles of AMPAR-MPR in rat lateral amygdala (LA) in short- and long-term fear memory formation, we used glutamate receptors (GluAs)-MPR competitive peptides MPR(DD) and MPR(AA). The MPR(DD) peptide is derived from GluA1 MPR and was previously shown to impair synaptic plasticity and to inhibit GluA1 containing AMPAR insertion into the synapse in an activity-dependent manner. The MPR(AA) peptide is derived from GluA2/4 MPR, and this receptor fragment was shown to be essential for GluA4 protein interaction needed for its insertion into the neuronal membrane and synapse. The peptides were linked to a TAT peptide (TAT-MPR(DD) and TAT-MPR(AA)) to facilitate internalization into LA cells. Infusion of the TAT-MPR(DD) peptide into LA 30 min before fear conditioning led to a significant impairment of long-term fear memory formation. Injection of TAT-MPR(DD) peptide into LA 30 min before fear conditioning impaired short-term fear memory formation. The TAT-MPR(DD) peptide had no effect on memory retrieval when injected into LA 30 min before fear memory test. Infusion of the TAT-MPR(AA) peptide into LA 30 min before fear conditioning led to a significant impairment of long-term fear memory formation. In contrast, the TAT-MPR(AA) had no effect on short-term fear memory formation. A TAT-control peptide had no effect on short- or long-term fear memory. These results show that the AMPAR-MPR in LA is needed for fear memory formation and that the MPR region of GluA1 is essential for acquisition of memory, whereas the MPR region of GluA4 is essential for long-term fear memory consolidation.
α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体（AMPAR）的膜近端区域（MPR）对于受体转运和突触可塑性是必需的。然而，其在长期记忆形成中的作用尚不清楚。为了评估AMPAR-MPR在大鼠外侧杏仁核（LA）短期和长期恐惧记忆形成中的可能作用，我们使用了谷氨酸受体（GluAs）-MPR竞争性肽MPR(DD)和MPR(AA)。MPR(DD)肽源自GluA1 MPR，先前已证明其会损害突触可塑性，并以活动依赖的方式抑制含有GluA1的AMPAR插入突触。MPR(AA)肽源自GluA2/4 MPR，并且该受体片段已被证明对于GluA4蛋白插入神经元膜和突触所需的相互作用至关重要。这些肽与TAT肽相连（TAT-MPR(DD)和TAT-MPR(AA)）以促进内化进入LA细胞。在恐惧条件反射前30分钟将TAT-MPR(DD)肽注入LA会导致长期恐惧记忆形成的显著损害。在恐惧条件反射前30分钟将TAT-MPR(DD)肽注入LA会损害短期恐惧记忆形成。当在恐惧记忆测试前30分钟将TAT-MPR(DD)肽注入LA时，它对记忆提取没有影响。在恐惧条件反射前30分钟将TAT-MPR(AA)肽注入LA会导致长期恐惧记忆形成的显著损害。相比之下，TAT-MPR(AA)对短期恐惧记忆形成没有影响。TAT对照肽对短期或长期恐惧记忆没有影响。这些结果表明，LA中的AMPAR-MPR是恐惧记忆形成所必需的，并且GluA1的MPR区域对于记忆获取至关重要，而GluA4的MPR区域对于长期恐惧记忆巩固至关重要。
