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- W3215880937 abstract "mGlu3 receptors control the sleep/wake architecture which plays a role in the glutamatergic pathophysiology of schizophrenia. Interestingly, mGlu3 receptors expression is decreased in the brain of schizophrenic patients. However, little is known about the molecular mechanisms regulating mGlu3 receptors at the cell membrane. Subcellular receptor localization is strongly dependent on protein-protein interactions. Here we show that mGlu3 interacts with PICK1 and that their binding is important for receptor surface expression and function. Disruption of their interaction via an mGlu3 C-terminal mimicking peptide or an inhibitor of the PDZ domain of PICK1 altered the functional expression of mGlu3 receptors. Consequently, we investigated whether disruption of the mGlu3-PICK1 interaction affects hippocampal theta oscillations in vitro and in vivo. We found a decreased frequency of theta oscillations in organotypic hippocampal slices, similar to what previously observed in mGlu3 -/- mice. In addition, hippocampal theta power was reduced during REM sleep, NREM sleep and wake states after intra-ventricular administration of the mGlu3 C-terminal mimicking peptide. Targeting the mGlu3-PICK1 complex could thus be relevant to the pathophysiology of schizophrenia." @default.
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- W3215880937 date "2021-11-19" @default.
- W3215880937 modified "2023-10-18" @default.
- W3215880937 title "Modulation of hippocampal network oscillation by PICK1-dependent cell surface expression of mGlu3 receptors" @default.
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- W3215880937 doi "https://doi.org/10.1101/2021.11.19.469240" @default.
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