Isoform-specific roles for AKT in affective behavior, spatial memory, and extinction related to psychiatric disorders
AKT is implicated in neurological disorders. AKT has three isoforms, AKT1/AKT2/AKT3, with brain cell type-specific expression that may differentially influence behavior. Therefore, we examined single Akt isoform, conditional brain-specific Akt1, and double Akt1/3 mutant mice in behaviors relevant to...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2020-12-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/56630 |
| _version_ | 1811199741494558720 |
|---|---|
| author | Helen Wong Josien Levenga Lauren LaPlante Bailey Keller Andrew Cooper-Sansone Curtis Borski Ryan Milstead Marissa Ehringer Charles Hoeffer |
| author_facet | Helen Wong Josien Levenga Lauren LaPlante Bailey Keller Andrew Cooper-Sansone Curtis Borski Ryan Milstead Marissa Ehringer Charles Hoeffer |
| author_sort | Helen Wong |
| collection | DOAJ |
| description | AKT is implicated in neurological disorders. AKT has three isoforms, AKT1/AKT2/AKT3, with brain cell type-specific expression that may differentially influence behavior. Therefore, we examined single Akt isoform, conditional brain-specific Akt1, and double Akt1/3 mutant mice in behaviors relevant to neuropsychiatric disorders. Because sex is a determinant of these disorders but poorly understood, sex was an experimental variable in our design. Our studies revealed AKT isoform- and sex-specific effects on anxiety, spatial and contextual memory, and fear extinction. In Akt1 mutant males, viral-mediated AKT1 restoration in the prefrontal cortex rescued extinction phenotypes. We identified a novel role for AKT2 and overlapping roles for AKT1 and AKT3 in long-term memory. Finally, we found that sex-specific behavior effects were not mediated by AKT expression or activation differences between sexes. These results highlight sex as a biological variable and isoform- or cell type-specific AKT signaling as potential targets for improving treatment of neuropsychiatric disorders. |
| first_indexed | 2024-04-12T01:52:25Z |
| format | Article |
| id | doaj.art-29951fa61b6c48d4a3d2d5fd4522644d |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T01:52:25Z |
| publishDate | 2020-12-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-29951fa61b6c48d4a3d2d5fd4522644d2022-12-22T03:52:53ZengeLife Sciences Publications LtdeLife2050-084X2020-12-01910.7554/eLife.56630Isoform-specific roles for AKT in affective behavior, spatial memory, and extinction related to psychiatric disordersHelen Wong0https://orcid.org/0000-0002-3927-8953Josien Levenga1https://orcid.org/0000-0002-9971-6337Lauren LaPlante2Bailey Keller3Andrew Cooper-Sansone4Curtis Borski5Ryan Milstead6https://orcid.org/0000-0002-3333-853XMarissa Ehringer7Charles Hoeffer8https://orcid.org/0000-0002-2036-0201Institute for Behavioral Genetics, University of Colorado, Boulder, United StatesInstitute for Behavioral Genetics, University of Colorado, Boulder, United States; Linda Crnic Institute, Anschutz Medical Center, Aurora, United StatesInstitute for Behavioral Genetics, University of Colorado, Boulder, United StatesInstitute for Behavioral Genetics, University of Colorado, Boulder, United StatesInstitute for Behavioral Genetics, University of Colorado, Boulder, United StatesInstitute for Behavioral Genetics, University of Colorado, Boulder, United StatesDepartment of Integrative Physiology, University of Colorado, Boulder, United StatesInstitute for Behavioral Genetics, University of Colorado, Boulder, United States; Department of Integrative Physiology, University of Colorado, Boulder, United StatesInstitute for Behavioral Genetics, University of Colorado, Boulder, United States; Linda Crnic Institute, Anschutz Medical Center, Aurora, United States; Department of Integrative Physiology, University of Colorado, Boulder, United StatesAKT is implicated in neurological disorders. AKT has three isoforms, AKT1/AKT2/AKT3, with brain cell type-specific expression that may differentially influence behavior. Therefore, we examined single Akt isoform, conditional brain-specific Akt1, and double Akt1/3 mutant mice in behaviors relevant to neuropsychiatric disorders. Because sex is a determinant of these disorders but poorly understood, sex was an experimental variable in our design. Our studies revealed AKT isoform- and sex-specific effects on anxiety, spatial and contextual memory, and fear extinction. In Akt1 mutant males, viral-mediated AKT1 restoration in the prefrontal cortex rescued extinction phenotypes. We identified a novel role for AKT2 and overlapping roles for AKT1 and AKT3 in long-term memory. Finally, we found that sex-specific behavior effects were not mediated by AKT expression or activation differences between sexes. These results highlight sex as a biological variable and isoform- or cell type-specific AKT signaling as potential targets for improving treatment of neuropsychiatric disorders.https://elifesciences.org/articles/56630extinctionhippocampusprefrontal cortexisoformassociative memoryspatial learning |
| spellingShingle | Helen Wong Josien Levenga Lauren LaPlante Bailey Keller Andrew Cooper-Sansone Curtis Borski Ryan Milstead Marissa Ehringer Charles Hoeffer Isoform-specific roles for AKT in affective behavior, spatial memory, and extinction related to psychiatric disorders eLife extinction hippocampus prefrontal cortex isoform associative memory spatial learning |
| title | Isoform-specific roles for AKT in affective behavior, spatial memory, and extinction related to psychiatric disorders |
| title_full | Isoform-specific roles for AKT in affective behavior, spatial memory, and extinction related to psychiatric disorders |
| title_fullStr | Isoform-specific roles for AKT in affective behavior, spatial memory, and extinction related to psychiatric disorders |
| title_full_unstemmed | Isoform-specific roles for AKT in affective behavior, spatial memory, and extinction related to psychiatric disorders |
| title_short | Isoform-specific roles for AKT in affective behavior, spatial memory, and extinction related to psychiatric disorders |
| title_sort | isoform specific roles for akt in affective behavior spatial memory and extinction related to psychiatric disorders |
| topic | extinction hippocampus prefrontal cortex isoform associative memory spatial learning |
| url | https://elifesciences.org/articles/56630 |
| work_keys_str_mv | AT helenwong isoformspecificrolesforaktinaffectivebehaviorspatialmemoryandextinctionrelatedtopsychiatricdisorders AT josienlevenga isoformspecificrolesforaktinaffectivebehaviorspatialmemoryandextinctionrelatedtopsychiatricdisorders AT laurenlaplante isoformspecificrolesforaktinaffectivebehaviorspatialmemoryandextinctionrelatedtopsychiatricdisorders AT baileykeller isoformspecificrolesforaktinaffectivebehaviorspatialmemoryandextinctionrelatedtopsychiatricdisorders AT andrewcoopersansone isoformspecificrolesforaktinaffectivebehaviorspatialmemoryandextinctionrelatedtopsychiatricdisorders AT curtisborski isoformspecificrolesforaktinaffectivebehaviorspatialmemoryandextinctionrelatedtopsychiatricdisorders AT ryanmilstead isoformspecificrolesforaktinaffectivebehaviorspatialmemoryandextinctionrelatedtopsychiatricdisorders AT marissaehringer isoformspecificrolesforaktinaffectivebehaviorspatialmemoryandextinctionrelatedtopsychiatricdisorders AT charleshoeffer isoformspecificrolesforaktinaffectivebehaviorspatialmemoryandextinctionrelatedtopsychiatricdisorders |