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AKT isoforms have distinct hippocampal expression and roles in synaptic plasticity

Josien Levenga, Helen Wong, Ryan A. Milstead, Bailey N. Keller, Lauren E. Laplante, View ORCID ProfileCharles A. Hoeffer
doi: https://doi.org/10.1101/168336
Josien Levenga
1Institute for Behavioral Genetics, University of Colorado-Boulder, Boulder, CO 80303
3Linda Crnic Institute, Anschutz Medical Campus, Aurora, CO 80045
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Helen Wong
1Institute for Behavioral Genetics, University of Colorado-Boulder, Boulder, CO 80303
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Ryan A. Milstead
2Department of Integrative Physiology, University of Colorado-Boulder, Boulder, CO 80303
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Bailey N. Keller
1Institute for Behavioral Genetics, University of Colorado-Boulder, Boulder, CO 80303
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Lauren E. Laplante
1Institute for Behavioral Genetics, University of Colorado-Boulder, Boulder, CO 80303
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Charles A. Hoeffer
1Institute for Behavioral Genetics, University of Colorado-Boulder, Boulder, CO 80303
2Department of Integrative Physiology, University of Colorado-Boulder, Boulder, CO 80303
3Linda Crnic Institute, Anschutz Medical Campus, Aurora, CO 80045
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  • ORCID record for Charles A. Hoeffer
  • For correspondence: Charles.Hoeffer@colorado.edu
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ABSTRACT

AKT is a kinase that regulates 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 that 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. 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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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted July 25, 2017.
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AKT isoforms have distinct hippocampal expression and roles in synaptic plasticity
Josien Levenga, Helen Wong, Ryan A. Milstead, Bailey N. Keller, Lauren E. Laplante, Charles A. Hoeffer
bioRxiv 168336; doi: https://doi.org/10.1101/168336
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AKT isoforms have distinct hippocampal expression and roles in synaptic plasticity
Josien Levenga, Helen Wong, Ryan A. Milstead, Bailey N. Keller, Lauren E. Laplante, Charles A. Hoeffer
bioRxiv 168336; doi: https://doi.org/10.1101/168336

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