| First Author | Placzek AN | Year | 2016 |
| Journal | Elife | Volume | 5 |
| PubMed ID | 27960077 | Mgi Jnum | J:269740 |
| Mgi Id | MGI:6208451 | Doi | 10.7554/eLife.17517 |
| Citation | Placzek AN, et al. (2016) eIF2alpha-mediated translational control regulates the persistence of cocaine-induced LTP in midbrain dopamine neurons. Elife 5:e17517 |
| abstractText | Recreational drug use leads to compulsive substance abuse in some individuals. Studies on animal models of drug addiction indicate that persistent long-term potentiation (LTP) of excitatory synaptic transmission onto ventral tegmental area (VTA) dopamine (DA) neurons is a critical component of sustained drug seeking. However, little is known about the mechanism regulating such long-lasting changes in synaptic strength. Previously, we identified that translational control by eIF2alpha phosphorylation (p-eIF2alpha) regulates cocaine-induced LTP in the VTA (Huang et al., 2016). Here we report that in mice with reduced p-eIF2alpha-mediated translation, cocaine induces persistent LTP in VTA DA neurons. Moreover, selectively inhibiting eIF2alpha-mediated translational control with a small molecule ISRIB, or knocking down oligophrenin-1-an mRNA whose translation is controlled by p-eIF2alpha-in the VTA also prolongs cocaine-induced LTP. This persistent LTP is mediated by the insertion of GluR2-lacking AMPARs. Collectively, our findings suggest that eIF2alpha-mediated translational control regulates the progression from transient to persistent cocaine-induced LTP. |
