PDZ domains 1 and 2 of PSD-95 are necessary for memory consolidation

SALLES A; KRAWCZYK MC; MALLON A; ROMANO A; BOCCIA MM

CABA

Congreso; 2nd FALAN CONGRESS; 2016

FALAN

PDZ domains are present in several diverse proteins, including PSD-95 where it was first described. These are protein-protein interaction domains that anchor membrane proteins and hold together signalling complexes. PSD-95 is a main component of the post-synaptic density and is a member of the MAGUK family of proteins, interacting closely with NMDA receptors, among others. AT010 is a stable, cell-permeable peptide that was designed to bind to the PDZ domains 1 and 2 of PSD-95 with high affinity. We hypothesized AT010 might modulate the interaction between PSD-95 and other proteins, affecting memory consolidation. In this work we show that intra-hippocampal injection of AT010 reversibly interferes with memory consolidation of the inhibitory avoidance paradigm in mice. Although previous work has shown that interfering with the PSD-95 complex with intrathecal injections of the peptide has an analgesic effect, we show that it does not impair nociception when injected locally in the hippocampus. Exploratory toxicity studies of intravenous injections of AT010 showed no signs of toxicity.