Sleep Deprivation in Rats Causes a Redistribution of Scaffold Proteins, NMDAR Subunits, mGluR1, Dopamine Receptor-1, and Their Heterocomplexes Between Synaptic and Extrasynaptic Membranes

Several studies show that sleep deprivation (SD) reduces hippocampal long-term potentiation (LTP) by disrupting glutamatergic transmission. Reorganization of glutamate receptor complexes through post-translational modifications, mobility, and protein-protein interactions in the postsynaptic area is crucial for regulating synaptic plasticity. The cognitive impairment caused by SD may result from a temporary shift of components of the multiprotein complex from the synaptic to the extrasynaptic region, possibly linked to a short-term decrease in glutamatergic transmission. Our results indicate that the levels of three main scaffold proteins—PSD-95, Shank, and Homer—that associate with glutamatergic synaptic organization decrease in synaptic membranes and increase at extrasynaptic sites during SD. This redistribution is associated with increased attachment of NMDAR subunits, mGluR1, and D1 receptors to these scaffold proteins in extrasynaptic regions. Analysis of NMDAR subunits shows that NR2B increases more than NR2A, thus changing the NR2B/NR2A ratio in extrasynaptic membranes during SD. Furthermore, the heterocomplex containing NR1, PSD-95, and D1R accumulates at extrasynaptic membranes but remains stable at synaptic membranes. The distribution of PSD-95 transiently increases in extrasynaptic membranes during SD and decreases during recovery periods. Additionally, phosphorylation of Fyn tyrosine kinases correlates with the extrasynaptic movement of proteins during sleep deprivation. The redistribution of glutamatergic proteins in the hippocampal synaptic membrane likely accounts for the transient reduction in synaptic plasticity during SD.