AKT isoforms have distinct hippocampal expression and roles in synaptic plasticity.
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.
Pubmed ID: 29173281 RIS Download
Research resources used in this publication
- icy (RRID:SCR_010587) (software resource)
- ImageQuant (RRID:SCR_014246) (data processing software)
- pClamp (RRID:SCR_011323) (software resource)
- SPSS (RRID:SCR_002865) (software resource)
- B6.Cg-Tg(Nes-cre)1Kln/J (RRID:IMSR_JAX:003771) (organism)
- STOCK Tg(Eno2-cre)39Jme/J (RRID:IMSR_JAX:005938) (organism)
- B6.129-Akt2tm1.2Mbb/J (RRID:IMSR_JAX:026475) (organism)
- B6.129S4(FVB)-Akt1tm2.2Mbb/J (RRID:IMSR_JAX:026474) (organism)
- B6.129P2(Cg)-Akt2tm1.1Mbb/J (RRID:IMSR_JAX:006966) (organism)
- B6.129P2-Akt1tm1Mbb/J (RRID:IMSR_JAX:004912) (organism)
Additional research tools detected in this publication
Antibodies used in this publication
- Alexa Fluor 647-AffiniPure Donkey Anti-Chicken IgY (IgG) (H+L) (min X Bov,Gt,GP,Sy Hms,Hrs,Hu,Ms,Rb,Rat,Shp Sr Prot) (RRID:AB_2340379)
- Alexa Fluor 488-AffiniPure Donkey Anti-Mouse IgG (H+L) (min X Bov,Ck,Gt,GP,Sy Hms,Hrs,Hu,Rb,Shp Sr Prot) (RRID:AB_2340846)
- Cy3-AffiniPure Donkey Anti-Rabbit IgG (H+L) (min X Bov,Ck,Gt,GP,Sy Hms,Hrs,Hu,Ms,Rat,Shp Sr Prot) (RRID:AB_2307443)
- p44/42 MAPK (Erk1/2) Antibody (RRID:AB_330744)
- p44/42 MAP kinase (phosphorylated Erk1/2) (RRID:AB_331646)
- Anti-Puromycin Antibody, clone 12D10 (RRID:AB_2566826)
- Rabbit Anti-S6 Ribosomal Protein Monoclonal Antibody, Unconjugated, Clone 5G10 (RRID:AB_331355)
- Phospho-S6 Ribosomal Protein (Ser235/236) (2F9) Rabbit mAb (RRID:AB_2181037)
- Anti-GluA1/GluR1 Glutamate Receptor Antibody (RRID:AB_2315839)
- GSK-3beta (27C10) Rabbit mAb (RRID:AB_490890)
- Phospho-GSK-3beta (Ser9) (5B3) Rabbit mAb (RRID:AB_2115201)
- Glial Fibrillary Acidic Protein (GFAP) (RRID:AB_2492125)
- RBFOX3/NeuN Antibody (RRID:AB_11036146)
- Mouse Anti-Actin, beta Monoclonal Antibody, Unconjugated, Clone mAbcam 8226 (RRID:AB_306371)
- Rabbit Anti-GAPDH Monoclonal Antibody, Unconjugated, Clone 14C10 (RRID:AB_561053)
- PDK1 Antibody (RRID:AB_2236832)
- Phospho-PDK1 (Ser241) Antibody (RRID:AB_2161919)
- Tuberin/TSC2 (28A7) Rabbit mAb (RRID:AB_10692893)
- Phospho-Tuberin/TSC2 (Ser939) Antibody (RRID:AB_2207796)
- Akt (pan) (11E7) Rabbit mAb (RRID:AB_2225340)
- Phospho-Akt (Ser473) (736E11) Rabbit mAb (RRID:AB_331170)
- Akt3 (E1Z3W) Rabbit mAb (RRID:AB_2716311)
- Akt3 (L47B1) Mouse mAb (RRID:AB_10859371)
- Akt3 (E2B6R) Rabbit mAb #14293 (RRID:AB_2629491)
- Phospho-Akt2 (Ser474) (D3H2) Rabbit mAb (Akt2 Specific) (RRID:AB_2630347)
- Rabbit Anti-Akt2 Monoclonal Antibody, Unconjugated, Clone 5B5 (RRID:AB_331162)
- Anti-AKT2 Antibody (aa214-451) LS-C156232 (RRID:AB_2716310)
- hnRNP K (D9A8) Rabbit mAb (RRID:AB_11178946)
- Akt1 (D9R8K) Rabbit mAb (RRID:AB_2716309)
- Rabbit Anti-Akt1 Monoclonal Antibody, Unconjugated, Clone C73H10 (RRID:AB_915788)
Associated grants
- Agency: NINDS NIH HHS, United States
Id: F31 NS083277 - Agency: NINDS NIH HHS, United States
Id: R01 NS086933 - Agency: NIMH NIH HHS, United States
Id: T32 MH019524
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This is a list of tools and resources that we have found mentioned in this publication.
GE Healthcare (tool)
RRID:SCR_000004
A commercial antibody supplier and provider of various services.
View all literature mentionsNeuroMab (tool)
RRID:SCR_003086
A national mouse monoclonal antibody generating resource for biochemical and immunohistochemical applications in mammalian brain. NeuroMabs are generated from mice immunized with synthetic and recombinant immunogens corresponding to components of the neuronal proteome as predicted from genomic and other large-scale cloning efforts. Comprehensive biochemical and immunohistochemical analyses of human, primate and non-primate mammalian brain are incorporated into the initial NeuroMab screening procedure. This yields a subset of mouse mAbs that are optimized for use in brain (i.e. NeuroMabs): for immunocytochemical-based imaging studies of protein localization in adult, developing and pathological brain samples, for biochemical analyses of subunit composition and post-translational modifications of native brain proteins, and for proteomic analyses of native brain protein networks. The NeuroMab facility was initially funded with a five-year U24 cooperative grant from NINDS and NIMH. The initial goal of the facility for this funding period is to generate a library of novel NeuroMabs against neuronal proteins, initially focusing on membrane proteins (receptors/channels/transporters), synaptic proteins, other neuronal signaling molecules, and proteins with established links to disease states. The scope of the facility was expanded with supplements from the NIH Blueprint for Neuroscience Research to include neurodevelopmental targets, the NIH Roadmap for Medical Research to include epigenetics targets, and NIH Office of Rare Diseases Research to include rare disease targets. These NeuroMabs will then be produced on a large scale and made available to the neuroscience research community on an inexpensive basis as tissue culture supernatants or purified immunoglobulin by Antibodies Inc. The UC Davis/NIH NeuroMab Facility makes NeuroMabs available directly to end users and is unable to accommodate sales to distributors for third party distribution. Note, NeuroMab antibodies are now offered through antibodiesinc.
View all literature mentionsC57BL/6J (tool)
RRID:IMSR_JAX:000664
Mus musculus with name C57BL/6J from IMSR.
View all literature mentionsAlexa Fluor 647-AffiniPure Donkey Anti-Chicken IgY (IgG) (H+L) (min X Bov,Gt,GP,Sy Hms,Hrs,Hu,Ms,Rb,Rat,Shp Sr Prot) (antibody)
RRID:AB_2340379
This unknown targets Chicken IgY (IgG) (H+L)
View all literature mentionsAlexa Fluor 488-AffiniPure Donkey Anti-Mouse IgG (H+L) (min X Bov,Ck,Gt,GP,Sy Hms,Hrs,Hu,Rb,Shp Sr Prot) (antibody)
RRID:AB_2340846
This unknown targets Mouse IgG (H+L)
View all literature mentionsCy3-AffiniPure Donkey Anti-Rabbit IgG (H+L) (min X Bov,Ck,Gt,GP,Sy Hms,Hrs,Hu,Ms,Rat,Shp Sr Prot) (antibody)
RRID:AB_2307443
This polyclonal targets IgG (H+L)
View all literature mentionsp44/42 MAPK (Erk1/2) Antibody (antibody)
RRID:AB_330744
This polyclonal targets p44/42 MAPK (Erk1/2)
View all literature mentionsp44/42 MAP kinase (phosphorylated Erk1/2) (antibody)
RRID:AB_331646
This polyclonal targets Erk1/2
View all literature mentionsAnti-Puromycin Antibody, clone 12D10 (antibody)
RRID:AB_2566826
This monoclonal targets Puromycin from Streptomyces alboniger
View all literature mentionsRabbit Anti-S6 Ribosomal Protein Monoclonal Antibody, Unconjugated, Clone 5G10 (antibody)
RRID:AB_331355
This monoclonal targets S6 Ribosomal Protein
View all literature mentionsPhospho-S6 Ribosomal Protein (Ser235/236) (2F9) Rabbit mAb (antibody)
RRID:AB_2181037
This monoclonal targets S6 Ribosomal Protein, phospho (Ser235 / Ser236)
View all literature mentionsAnti-GluA1/GluR1 Glutamate Receptor Antibody (antibody)
RRID:AB_2315839
This monoclonal targets GluA1/GluN1 glutamate receptor
View all literature mentionsGSK-3beta (27C10) Rabbit mAb (antibody)
RRID:AB_490890
This monoclonal targets GSK-3beta (27C10) Rabbit mAb
View all literature mentionsPhospho-GSK-3beta (Ser9) (5B3) Rabbit mAb (antibody)
RRID:AB_2115201
This monoclonal targets Phospho-GSK-3beta (Ser9)
View all literature mentionsGlial Fibrillary Acidic Protein (GFAP) (antibody)
RRID:AB_2492125
This polyclonal targets GFAP
View all literature mentionsRBFOX3/NeuN Antibody (antibody)
RRID:AB_11036146
This monoclonal targets RBFOX3/NeuN
View all literature mentionsMouse Anti-Actin, beta Monoclonal Antibody, Unconjugated, Clone mAbcam 8226 (antibody)
RRID:AB_306371
This monoclonal targets beta Actin
View all literature mentionsRabbit Anti-GAPDH Monoclonal Antibody, Unconjugated, Clone 14C10 (antibody)
RRID:AB_561053
This recombinant monoclonal targets GAPDH
View all literature mentionsPhospho-PDK1 (Ser241) Antibody (antibody)
RRID:AB_2161919
This unknown targets PDK1, phospho (Ser241)
View all literature mentionsTuberin/TSC2 (28A7) Rabbit mAb (antibody)
RRID:AB_10692893
This monoclonal targets TSC2
View all literature mentionsPhospho-Tuberin/TSC2 (Ser939) Antibody (antibody)
RRID:AB_2207796
This polyclonal targets Phospho-Tuberin/TSC2 (Ser939)
View all literature mentionsAkt (pan) (11E7) Rabbit mAb (antibody)
RRID:AB_2225340
This monoclonal targets Akt2
View all literature mentionsPhospho-Akt (Ser473) (736E11) Rabbit mAb (antibody)
RRID:AB_331170
This monoclonal targets Phospho-Akt (Ser473) (736E11) Rabbit mAb
View all literature mentionsAkt3 (E1Z3W) Rabbit mAb (antibody)
RRID:AB_2716311
This monoclonal targets Akt3
View all literature mentionsAkt3 (L47B1) Mouse mAb (antibody)
RRID:AB_10859371
This monoclonal targets Akt3 (L47B1) Mouse mAb
View all literature mentionsAkt3 (E2B6R) Rabbit mAb #14293 (antibody)
RRID:AB_2629491
This monoclonal targets Total Akt3 Protein
View all literature mentionsPhospho-Akt2 (Ser474) (D3H2) Rabbit mAb (Akt2 Specific) (antibody)
RRID:AB_2630347
This monoclonal targets
View all literature mentionsRabbit Anti-Akt2 Monoclonal Antibody, Unconjugated, Clone 5B5 (antibody)
RRID:AB_331162
This monoclonal targets Akt2
View all literature mentionsAnti-AKT2 Antibody (aa214-451) LS-C156232 (antibody)
RRID:AB_2716310
This monoclonal targets Akt2
View all literature mentionshnRNP K (D9A8) Rabbit mAb (antibody)
RRID:AB_11178946
This monoclonal targets hnRNP K (D9A8) Rabbit mAb
View all literature mentionsAkt1 (D9R8K) Rabbit mAb (antibody)
RRID:AB_2716309
This monoclonal targets Akt1
View all literature mentionsRabbit Anti-Akt1 Monoclonal Antibody, Unconjugated, Clone C73H10 (antibody)
RRID:AB_915788
This monoclonal targets Akt1
View all literature mentionsicy (software resource)
RRID:SCR_010587
An open community platform for bioimage informatics providing the software resources to visualize, annotate and quantify bioimaging data. To bridge the gap between developers and users, it combines: a) an open-source image analysis software, offering a powerful and flexible environment for developers such as applied mathematicians to write algorithms fast and efficiently; b) a common set of tools to view and manipulate data, and a set of plugins to perform specific quantification or analysis on images; c) a community-based website centralizing all plugins and resources to facilitate their management and maximize their visibility towards users. Workspaces are virtual groups of plugins dedicated to a specific application or image processing domain. By downloading a workspace, ICY automatically installs all corresponding plugins. The workspaces are enabled, but the editing section is not ready yet. If you want to publish a plugin on this website, its code has to be GPL. Source code is available and provided in each application download.
View all literature mentionsImageQuant (data processing software)
RRID:SCR_014246
Software for automatic general image analysis. It provides fully automatic analysis of 1-D gels including lane creation, background subtraction, band detection, molecular weight calibration, quantity calibration, and normalization. Editing tools are provided for cropping, rotating, and filtering images.
View all literature mentionspClamp (software resource)
RRID:SCR_011323
Software suite for electrophysiology data acquisition and analysis by Molecular Devices. Used for the control and recording of voltage clamp, current clamp, and patch clamp experiments. The software suite consists of Clampex 11 Software for data acquisition, AxoScope 11 Software for background recording, Clampfit 11 Software for data analysis, and optional Clampfit Advanced Analysis Module for sophisticated and streamlined analysis.
View all literature mentionsSPSS (software resource)
RRID:SCR_002865
Software package used for interactive, or batched, statistical analysis in social science, health sciences and marketing. Software platform offers advanced statistical analysis, a library of machine-learning algorithms, text analysis, open-source extensibility, integration with big data and deployment into applications.Versions that were produced by SPSS Inc. before the IBM acquisition (Versions 18 and earlier) would be given origin or publisher of SPSS Inc. in Chicago.
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RRID:IMSR_JAX:003771
Mus musculus with name B6.Cg-Tg(Nes-cre)1Kln/J from IMSR.
View all literature mentionsSTOCK Tg(Eno2-cre)39Jme/J (organism)
RRID:IMSR_JAX:005938
NSE39-Cre transgenic mice harbor a transgenic insert consisting of the cre recombinase gene under the control of the promoter region of the rat neuron specific enolase (NSE or Eno2) gene. Cre recombinase activity is directed to neurons with expression in many tissue types, and may be useful in studies of spinal muscular atrophy (SMA). This is a legacy resource.
View all literature mentionsB6.129-Akt2tm1.2Mbb/J (organism)
RRID:IMSR_JAX:026475
Mus musculus with name B6.129-Akt2tm1.2Mbb/J from IMSR.
View all literature mentionsB6.129S4(FVB)-Akt1tm2.2Mbb/J (organism)
RRID:IMSR_JAX:026474
Mus musculus with name B6.129S4(FVB)-Akt1tm2.2Mbb/J from IMSR.
View all literature mentionsB6.129P2(Cg)-Akt2tm1.1Mbb/J (organism)
RRID:IMSR_JAX:006966
Mus musculus with name B6.129P2(Cg)-Akt2tm1.1Mbb/J from IMSR.
View all literature mentionsB6.129P2-Akt1tm1Mbb/J (organism)
RRID:IMSR_JAX:004912
Mus musculus with name B6.129P2-Akt1tm1Mbb/J from IMSR.
View all literature mentions
