eIF2α-mediated translational control regulates the persistence of cocaine-induced LTP in midbrain dopamine neurons
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 susta...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2016-12-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/17517 |
| _version_ | 1811235877453561856 |
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| author | Andon N Placzek Gonzalo Viana Di Prisco Sanjeev Khatiwada Martina Sgritta Wei Huang Krešimir Krnjević Randal J Kaufman John A Dani Peter Walter Mauro Costa-Mattioli |
| author_facet | Andon N Placzek Gonzalo Viana Di Prisco Sanjeev Khatiwada Martina Sgritta Wei Huang Krešimir Krnjević Randal J Kaufman John A Dani Peter Walter Mauro Costa-Mattioli |
| author_sort | Andon N Placzek |
| collection | DOAJ |
| description | 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 eIF2α phosphorylation (p-eIF2α) regulates cocaine-induced LTP in the VTA (Huang et al., 2016). Here we report that in mice with reduced p-eIF2α-mediated translation, cocaine induces persistent LTP in VTA DA neurons. Moreover, selectively inhibiting eIF2α-mediated translational control with a small molecule ISRIB, or knocking down oligophrenin-1—an mRNA whose translation is controlled by p-eIF2α—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 eIF2α-mediated translational control regulates the progression from transient to persistent cocaine-induced LTP. |
| first_indexed | 2024-04-12T11:59:39Z |
| format | Article |
| id | doaj.art-e0c309c78ecc447d856c18506ced27fe |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T11:59:39Z |
| publishDate | 2016-12-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-e0c309c78ecc447d856c18506ced27fe2022-12-22T03:33:55ZengeLife Sciences Publications LtdeLife2050-084X2016-12-01510.7554/eLife.17517eIF2α-mediated translational control regulates the persistence of cocaine-induced LTP in midbrain dopamine neuronsAndon N Placzek0Gonzalo Viana Di Prisco1Sanjeev Khatiwada2Martina Sgritta3Wei Huang4Krešimir Krnjević5Randal J Kaufman6John A Dani7Peter Walter8Mauro Costa-Mattioli9Department of Neuroscience, Baylor College of Medicine, Houston, United States; Memory and Brain Research Center, Baylor College of Medicine, Houston, United StatesDepartment of Neuroscience, Baylor College of Medicine, Houston, United States; Memory and Brain Research Center, Baylor College of Medicine, Houston, United StatesDepartment of Neuroscience, Baylor College of Medicine, Houston, United States; Memory and Brain Research Center, Baylor College of Medicine, Houston, United States; Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, United StatesDepartment of Neuroscience, Baylor College of Medicine, Houston, United States; Memory and Brain Research Center, Baylor College of Medicine, Houston, United StatesDepartment of Neuroscience, Baylor College of Medicine, Houston, United States; Memory and Brain Research Center, Baylor College of Medicine, Houston, United StatesDepartment of Physiology, McGill University, Montreal, CanadaDegenerative Diseases Program, SBP Medical Discovery Institute, La Jolla, United StatesDepartment of Neuroscience, Mahoney Institute for Neurosciences, Perelman School of Medicine, Philadelphia, United StatesDepartment of Biochemistry and Biophysics, Howard Hughes Medical Institute, University of California at San Francisco, San Francisco, United StatesDepartment of Neuroscience, Baylor College of Medicine, Houston, United States; Memory and Brain Research Center, Baylor College of Medicine, Houston, United StatesRecreational 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 eIF2α phosphorylation (p-eIF2α) regulates cocaine-induced LTP in the VTA (Huang et al., 2016). Here we report that in mice with reduced p-eIF2α-mediated translation, cocaine induces persistent LTP in VTA DA neurons. Moreover, selectively inhibiting eIF2α-mediated translational control with a small molecule ISRIB, or knocking down oligophrenin-1—an mRNA whose translation is controlled by p-eIF2α—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 eIF2α-mediated translational control regulates the progression from transient to persistent cocaine-induced LTP.https://elifesciences.org/articles/17517synaptic plasticitypsychostimulant abuseprotein synthesisAMPARdrug addiciton |
| spellingShingle | Andon N Placzek Gonzalo Viana Di Prisco Sanjeev Khatiwada Martina Sgritta Wei Huang Krešimir Krnjević Randal J Kaufman John A Dani Peter Walter Mauro Costa-Mattioli eIF2α-mediated translational control regulates the persistence of cocaine-induced LTP in midbrain dopamine neurons eLife synaptic plasticity psychostimulant abuse protein synthesis AMPAR drug addiciton |
| title | eIF2α-mediated translational control regulates the persistence of cocaine-induced LTP in midbrain dopamine neurons |
| title_full | eIF2α-mediated translational control regulates the persistence of cocaine-induced LTP in midbrain dopamine neurons |
| title_fullStr | eIF2α-mediated translational control regulates the persistence of cocaine-induced LTP in midbrain dopamine neurons |
| title_full_unstemmed | eIF2α-mediated translational control regulates the persistence of cocaine-induced LTP in midbrain dopamine neurons |
| title_short | eIF2α-mediated translational control regulates the persistence of cocaine-induced LTP in midbrain dopamine neurons |
| title_sort | eif2α mediated translational control regulates the persistence of cocaine induced ltp in midbrain dopamine neurons |
| topic | synaptic plasticity psychostimulant abuse protein synthesis AMPAR drug addiciton |
| url | https://elifesciences.org/articles/17517 |
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