AKT isoforms have distinct hippocampal expression and roles in synaptic plasticity
- University of Colorado, Boulder, United States
Abstract
AKT is a kinase regulating numerous cellular processes in the brain and mutations in AKT are known to affect brain function. AKT is indirectly implicated in synaptic plasticity, but its direct role has not been studied. Moreover, three highly related AKT isoforms are expressed in the brain, but their individual roles are poorly understood. We find in Mus musculus, each AKT isoform has a unique expression pattern in the hippocampus, with AKT1 and AKT3 primarily in neurons but displaying local differences, while AKT2 is in astrocytes. We also find isoform-specific roles for AKT in multiple paradigms of hippocampal synaptic plasticity in area CA1. AKT1, but not AKT2 or AKT3, is required for L-LTP through regulating activity-induced protein synthesis. Interestingly, AKT activity inhibits mGluR-LTD, with overlapping functions for AKT1 and AKT3. In summary, our studies identify distinct expression patterns and roles in synaptic plasticity for AKT isoforms in the hippocampus.
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Author details
Funding
Alzheimer's Association (MNIRGDP-12-258900)
- Charles A Hoeffer
Simons Foundation (SFARI 27444)
- Charles A Hoeffer
National Institutes of Health (R01 NS086933)
- Charles A Hoeffer
Linda Crnic Institute Seed Grant
- Charles A Hoeffer
Sie Foundation
- Josien Levenga
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All animals used in this study were handled according to the approved institutional animal care and use committee (IACUC) protocols (1311.02, 2541) of the University of Colorado-Boulder.
Copyright
© 2017, Levenga et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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AKT isoforms have distinct hippocampal expression and roles in synaptic plasticity
eLife 6:e30640.
https://doi.org/10.7554/eLife.30640
