Metabotropic glutamate type 5 receptor requires contactin‐associated protein 1 to control memory formation

Abstract The hippocampus is a key brain region for memory formation. Metabotropic glutamate type 5 receptors (mGlu5R) are strongly expressed in CA1 pyramidal neurons and fine‐tune synaptic plasticity. Accordingly, mGlu5R pharmacological manipulation may represent an attractive therapeutic strategy to manage hippocampal‐related neurological disorders. Here, by means of a membrane yeast two‐hybrid screening, we identified contactin‐associated protein 1 (Caspr1), a type I transmembrane protein member of the neurexin family, as a new mGlu5R partner. We report that mGlu5R and Caspr1 co‐distribute and co‐assemble both in heterologous expression systems and in rat brain. Furthermore, downregulation of Caspr1 in rat hippocampal primary cultures decreased mGlu5R‐mediated signaling. Finally, silencing Caspr1 expression in the hippocampus impaired the impact of mGlu5R on spatial memory. Our results indicate that Caspr1 plays a pivotal role controlling mGlu5R function in hippocampus‐dependent memory formation. Hence, this new protein‐protein interaction may represent novel target for neurological disorders affecting hippocampal glutamatergic neurotransmission.

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