Key role of NF-kB for memory consolidation in fear conditioning in fish

A. BARBOSA JÚNIOR; A. HOFFMANN; L. M. IDE; R. FREUDENTHAL; A. ROMANO; S. MORATO

San Diego

Encuentro; Anual Meeting Society for Neuroscience; 2013

Society for Neuroscience

Although it is generally accepted that memory consolidation requires regulation of gene expression, only a few transcription factors (TFs) have been clearly demonstrated to be specifically involved in this process. NF-κB is an evolutionarily conserved family of TFs critically involved in basic cellular mechanisms of the immune response, inflammation, development and apoptosis. Recently, an increasing number of reports have called attention to the role of NF-κB in processes that require long-term regulation of the synaptic function underlying memory and neural plasticity in crabs and mammals, but not in fish. This works presents data supporting a role of the TF NF-κB in fear memory consolidation in the South American freshwater fish Leporinus macrocephalus. To assess the effect of inhibiting NFkB signaling on memory consolidation, vehicle or drug sulfasalazine (SSZ, 3.5mM and 5mM), a direct pharmacological inhibitor of NF-kB pathway, were administered intracerebroventricularly at a volume of 1ul immediately after training session. During training, an initially neutral conditioned stimulus (CS, a blue light) was associated with a fear unconditioned stimulus (US, the alarm pheromone) that elicit freezing behavior. After training, the vehicle or SSZ were administered and a retention memory test (only CS-exposed) was performed 24h after drug infusion. During training all experimental groups displayed freezing behavior and significant reduction in the behavioral endpoints (distance traveled, velocity in swimming, movement duration and the time spent in the top of the aquarium). In vehicle-treated animals, freezing behavior and reduction in the behavioral endpoints were observed during memory retention test session. However, intracerebroventricular infusion of SSZ 3.5mM and 5mM, an inhibitor of IkB kinase that activates the NB-kB, immediately after training disrupted the consolidation of fear conditioning in L. macrocephalus. Freezing behavior and a significant reduction in behavioral endpoints were not observed in SSZ-treated animals during retention memory test. This is the first work to demonstrate a specifically role of NF-kB in memory process in fish. These results suggest a key evolutionary-conserved role of the NF-kB TF in memory storage and maintenance.