Cognition, Behavior, and Memory
Author: Agustina Denise Robles | email: agusd.robles@gmail.com
Agustina Robles 1°, Arturo Romano 1°
1° Instituto de Fisiología, Biología Molecular y Neurociencias, Departamento de Fisiología, Biología Molecular y Celular, CONICET, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires
HDAC3 has been associated with memory formation processes, acting as a negative modulator that represses memory related gene expression. It was also observed that transcription during memory consolidation occurs within a definite time window and in waves. In this study, we aimed to determine the effect of HDAC3 inhibition at different time points after a weak learning session on long-term memory consolidation using the Novel Object Recognition (NOR) and Fear Conditioning (FC) tasks in mice. HDAC3 inhibitor RGFP966 has a facilitating effect producing a memory that lasts up to 7 days in the NOR task only when administered immediately or 6 hours after training. In contrast, administration at 3 or 9 hours after training had no effect compared to vehicle injected controls. However, this facilitating effect was not observed in the FC task. These two points of sensitivity found in the NOR task match with two waves of transcriptional activity described in rats and with two waves of NF-kB activation reported in crabs, the latter being partly regulated by HDAC3 which inactivates it by p65 deacetilation. Ongoing experiments are being conducted to elucidate the link between NF-kB and HDAC3. We hypothesize that mice also have two waves of NF-kB activation and transcriptional activity during memory consolidation, but under weak training conditions HDAC3 would be blocking long-term memory formation by repressing gene expression through histone deacetilation and NF-kB inactivation.