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

ANGELES SALLES; MARIA DEL CARMEN KRAWCZYK; ANDREW MALLON; ARTURO ROMANO; MARIANO BOCCIA; RAMIRO FREUDENTHAL

Buenos Aires

Congreso; 2nd Congress of the Federation of Latin-American and Caribbean Societies for Neuroscience (FALAN); 2016

Congreso FALAN 2016 - Buenos Aires, Argentina

PDZ domains are present in several diverse proteins, including PSD-95 where it was first described. These are protein-protein interaction domains that anchormembrane proteins and hold together signaling complexes. PSD-95 is a main component of the post-synaptic density and is a member of the MAGUK family ofproteins, interacting closely with NMDA receptors, among others. We used a stable, cell-permeable peptide that was designed to bind to the PDZ domains 1 and 2 ofPSD-95 with high affinity and we hypothesized that this peptide might modulate the interaction between PSD-95 and other proteins, affecting memory consolidation. Inthis work we show that intra-hippocampal injection of this peptide 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 notimpair nociception when injected locally in the hippocampus. Exploratory toxicity studies of intravenous injections of the peptide showed no signs of toxicity.