Retrieval-specific endocytosis of GluA2-AMPARs underlies adaptive reconsolidation of contextual fear

Priyanka Rao-Ruiz (1) , Diana C. Rotaru (1) , Rolinka J van Der Loo (1) , Huibert Mansvelder (1) , Oliver Stiedl (1) , August B Smit (1) , Sabine Spijker (1)

1 Molecular & Cellular Neurobiology

Upon retrieval, fear memories are rendered labile and prone to modifications, necessitating a restabilization process of reconsolidation to persist further. This process is also crucial to modulate both strength and content of an existing memory and forms a promising therapeutic target for fear-related disorders. However, the molecular and cellular mechanism of adaptive reconsolidation still remains obscure. Here, we show that retrieval of fear memory induces a biphasic temporal change in GluA2-containing α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor (AMPAR) membrane expression and synaptic strength in the mouse dorsal hippocampus. Blocking retrieval-induced regulated GluA2-dependent endocytosis enhanced subsequent expression of fear. In addition, this blockade prevented the loss of fear response after reconsolidation-update of fear memory content on the long-term. Thus, endocytosis of GluA2-containing AMPARs allows plastic changes at the synaptic level that exerts an inhibitory constraint on memory strengthening, and underlies the loss of fear response by reinterpretation of memory content during adaptive reconsolidation.

Mots clés: Memory; Receptors; Plasticity; Synaptic Transmission

Domaines: Neurosciences [q-bio.NC]

Priyanka Rao-Ruiz, Diana C. Rotaru, Rolinka J van Der Loo, Huibert Mansvelder, Oliver Stiedl, et al.. Retrieval-specific endocytosis of GluA2-AMPARs underlies adaptive reconsolidation of contextual fear. Nature Neuroscience, 2011, ⟨10.1038/nn.2907⟩. ⟨hal-00677961⟩