ABSTRACT
Ubiquitination is involved in synaptic plasticity and memory, but the involvement of HECT E3 ligases in these processes has not yet been established. Here, we bilaterally infused heclin, a specific inhibitor of some of these ligases, into the dorsal hippocampus of male Wistar rats that were trained in a contextual fear conditioning. Heclin improved short-term memory, consolidation, retrieval, and reconsolidation when administered immediately post training, prior to testing, or after memory reactivation, respectively. In addition, it impaired memory extinction when administered prior to a long reactivation session. Heclin infusion was also tested for locomotor activity and anxiety-like behavior in a circular arena, but no effect was seen. Taken together, these results indicate that HECT E3 ligases are involved in the modulation of fear memory.
Subject(s)
Conditioning, Classical/physiology , Fear/physiology , Hippocampus/physiology , Memory/physiology , Ubiquitin-Protein Ligases/physiology , Acrylamides/administration & dosage , Acrylamides/pharmacology , Animals , Conditioning, Classical/drug effects , Enzyme Inhibitors/administration & dosage , Enzyme Inhibitors/pharmacology , Extinction, Psychological/drug effects , Extinction, Psychological/physiology , Furans/administration & dosage , Furans/pharmacology , Hippocampus/drug effects , Male , Memory/drug effects , Memory Consolidation/drug effects , Memory Consolidation/physiology , Mental Recall/drug effects , Mental Recall/physiology , Rats, Wistar , Ubiquitin-Protein Ligases/antagonists & inhibitorsABSTRACT
It has been proposed that long-lasting changes in dendritic spines provide a physical correlate for memory formation and maintenance. Spine size and shape are highly plastic, controlled by actin polymerization/depolymerization cycles. This actin dynamics are regulated by proteins such as calpain, a calcium-dependent cysteine protease that cleaves the structural cytoskeleton proteins and other targets involved in synaptic plasticity. Here, we tested whether the pharmacological inhibition of calpain in the dorsal hippocampus affects memory consolidation, retrieval and reconsolidation in rats trained in contextual fear conditioning. We first found that post-training infusion of the calpain inhibitor PD150606 impaired long-term memory consolidation, but not short-term memory. Next, we showed that pre-test infusion of the calpain inhibitor hindered memory retrieval. Finally, blocking calpain activity after memory reactivation disrupted reconsolidation. Taken together, our results show that calpain play an essential role in the hippocampus by enabling memory formation, expression and reconsolidation.
