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Homeostatic Changes in GABA and Glutamate Receptors on Excitatory Cortical Neurons during Sleep Deprivation and Recovery.

Frontiers in systems neuroscience | 2017

Neuronal activity is regulated in a homeostatic manner through changes in inhibitory GABA and excitatory glutamate (Glu) AMPA (A) receptors (GluARs). Using immunofluorescent staining, we examined whether calcium/calmodulin-dependent protein kinase IIα (CaMKIIα)-labeled (+) excitatory neurons in the barrel cortex undergo such homeostatic regulation following enforced waking with associated cortical activation during the day when mice normally sleep the majority of the time. Sleep deprived mice were prevented from falling asleep by unilateral whisker stimulation and sleep recovery (SR) mice allowed to sleep freely following deprivation. In parallel with changes in c-Fos reflecting changes in activity, (β2-3 subunits of) GABAA Rs were increased on the membrane of CaMKIIα+ neurons with enforced waking and returned to baseline levels with SR in barrel cortex on sides both contra- and ipsilateral to the whisker stimulation. The GABAAR increase was correlated with increased gamma electroencephalographic (EEG) activity across conditions. On the other hand, (GluA1 subunits of) AMPA Rs were progressively removed from the membrane of CaMKIIα+ neurons by (Rab5+) early endosomes during enforced waking and returned to the membrane by (Rab11+) recycling endosomes during SR. The internalization of the GluA1Rs paralleled the expression of Arc, which mediates homeostatic regulation of AMPA receptors through an endocytic pathway. The reciprocal changes in GluA1Rs relative to GABAARs suggest homeostatic down-scaling during enforced waking and sensory stimulation and restorative up-scaling during recovery sleep. Such homeostatic changes with sleep-wake states and their associated cortical activities could stabilize excitability and activity in excitatory cortical neurons.

Pubmed ID: 28408870 RIS Download

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Thermo Fisher Scientific (tool)

RRID:SCR_008452

Commercial vendor and service provider of laboratory reagents and antibodies. Supplier of scientific instrumentation, reagents and consumables, and software services.

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FISHER (tool)

RRID:SCR_009181

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Adobe Illustrator (tool)

RRID:SCR_010279

Vector graphics software to create digital graphics, illustrations, and typography for several types of media: print, web, interactive, video, and mobile.

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Adobe Photoshop (tool)

RRID:SCR_014199

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C57BL/6J (tool)

RRID:IMSR_JAX:000664

Mus musculus with name C57BL/6J from IMSR.

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Rab11 antibody (antibody)

RRID:AB_10861613

This polyclonal targets Rab11 antibody

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Rab5 antibody - Early Endosome Marker (antibody)

RRID:AB_470264

This polyclonal targets Rab5 antibody - Early Endosome Marker

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Rab11 antibody [KT80] (antibody)

RRID:AB_10688715

This monoclonal targets Rab11 antibody [KT80]

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Rab5 antibody [3A4] (antibody)

RRID:AB_1141650

This monoclonal targets Rab5 antibody [3A4]

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Anti-Glutamate receptor 1 (antibody)

RRID:AB_2113602

This polyclonal targets Glutamate receptor 1

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Anti-GABA A Receptor beta 2,3 Chain, extracellular domain of the beta2 & beta3 subunits of the GABA A receptor, clone BD17 (antibody)

RRID:AB_2109419

This monoclonal targets GABA A Receptor beta 23 Chain extracellular domain of the beta2 & beta3 subunits of the GABA A receptor clone BD17

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Anti-Arc (antibody)

RRID:AB_887694

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CaMKII alpha Polyclonal Antibody (antibody)

RRID:AB_2070314

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Rab11 antibody (antibody)

RRID:AB_10861613

This polyclonal targets Rab11 antibody

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Rab5 antibody - Early Endosome Marker (antibody)

RRID:AB_470264

This polyclonal targets Rab5 antibody - Early Endosome Marker

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Rab11 antibody [KT80] (antibody)

RRID:AB_10688715

This monoclonal targets Rab11 antibody [KT80]

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Rab5 antibody [3A4] (antibody)

RRID:AB_1141650

This monoclonal targets Rab5 antibody [3A4]

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Anti-Glutamate receptor 1 (antibody)

RRID:AB_2113602

This polyclonal targets Glutamate receptor 1

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Anti-GABA A Receptor beta 2,3 Chain, extracellular domain of the beta2 & beta3 subunits of the GABA A receptor, clone BD17 (antibody)

RRID:AB_2109419

This monoclonal targets GABA A Receptor beta 23 Chain extracellular domain of the beta2 & beta3 subunits of the GABA A receptor clone BD17

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Anti-Arc (antibody)

RRID:AB_887694

This polyclonal targets Arc

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CaMKII alpha Polyclonal Antibody (antibody)

RRID:AB_2070314

This unknown targets CaMKII alpha

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Rab11 antibody (antibody)

RRID:AB_10861613

This polyclonal targets Rab11 antibody

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Rab5 antibody - Early Endosome Marker (antibody)

RRID:AB_470264

This polyclonal targets Rab5 antibody - Early Endosome Marker

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Rab11 antibody [KT80] (antibody)

RRID:AB_10688715

This monoclonal targets Rab11 antibody [KT80]

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Rab5 antibody [3A4] (antibody)

RRID:AB_1141650

This monoclonal targets Rab5 antibody [3A4]

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Anti-Glutamate receptor 1 (antibody)

RRID:AB_2113602

This polyclonal targets Glutamate receptor 1

View all literature mentions

Anti-GABA A Receptor beta 2,3 Chain, extracellular domain of the beta2 & beta3 subunits of the GABA A receptor, clone BD17 (antibody)

RRID:AB_2109419

This monoclonal targets GABA A Receptor beta 23 Chain extracellular domain of the beta2 & beta3 subunits of the GABA A receptor clone BD17

View all literature mentions

Anti-Arc (antibody)

RRID:AB_887694

This polyclonal targets Arc

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CaMKII alpha Polyclonal Antibody (antibody)

RRID:AB_2070314

This unknown targets CaMKII alpha

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