Sleep Deprivation in Rats Causes Dissociation of the Synaptic NMDA Receptor/D1 Dopamine Receptor Heterocomplex

TL;DR

Sleep deprivation in rats disrupts specific receptor complexes in the brain, affecting synaptic plasticity and actin structures.

Contribution

This study reveals that sleep deprivation causes dissociation of a specific synaptic receptor complex involving NMDA, D1 dopamine, and Homer proteins.

Findings

Sleep deprivation reduces Homer in the GluN2A/mGluR1/D1R complex but not in GluN2B/mGluR1/D2R.

SD decreases the Homer/IP3R interaction, indicating dissociation of the Homer/mGluR1/IP3R supercomplex.

Sleep deprivation increases synaptic GluA1 and alters actin filament assembly via cofilin dephosphorylation.

Abstract

Glutamate and dopamine receptors play a crucial role in regulating synaptic plasticity throughout the sleep–wake cycle. These receptors form various heterocomplexes in synaptic areas; however, the role of this protein interactome in sleep–wake cycles remains unclear. Co-immunoprecipitation experiments were conducted to observe the complexation of the NMDA glutamate receptor (NMDAR) subunits GluN2A and GluN2B, metabotropic glutamate receptors mGluR1/5, and dopamine receptors (D1R and D2R) with the scaffold protein Homer in the synaptic membranes of the hippocampus after six hours of sleep deprivation (SD) in rats. Our findings indicate that the level of Homer in the GluN2A/mGluR1/D1R interactome decreased during SD, while the content of Homer remained unchanged in the GluN2B/mGluR1/D2R heterocomplex. Moreover, Homer immunoprecipitated a reduced amount of inositol trisphosphate receptor (IP3R) in the microsomal and synaptic fractions, confirming the dissociation of the ternary supercomplex Homer/mGluR1/IP3R during SD. Additionally, our findings indicate that SD increases the synaptic content of the AMPA receptor (AMPAR) subunit GluA1. Unlike AMPAR, NMDAR subunits in synaptic membranes do not undergo significant changes. Furthermore, the G-to-F actin ratio decreases during SD. Changes in the assembly of actin filaments occur due to the dephosphorylation of cofilin. These results suggest that SD causes the dissociation of the GluN2A/mGluR1/D1R/Homer/IP3R heterocomplex in synaptic and endoplasmic membranes.

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