Late changes in protein levels after one-trial inhibitory avoidance learning depend upon training

PEDRO BEKINSCHTEIN; LIONEL MÜLLER IGAZ; IVAN IZQUIERDO; MARTÍN CAMMAROTA; JORGE H. MEDINA

New York, USA

Congreso; 35th Annual Meeting . American Society for Neurochemistry; 2004

American Society for Neurochemistry

It is widely accepted that formation of long-term memory requires gene expression and de novo protein synthesis. We analyzed the temporal expression profile of candidate gene products regulated by one-trial inhibitory avoidance (IA) learning. Although hippocampal mRNA changes were detected 3 hours (h) after IA training (not shown), most protein level changes were not detected until 18 to 24 h after. This was the case for CaMKIIa, Erk-2, syntaxin-1a, c-fos, homer-1a and Akt. Significant increases in Casein Kinase Ila and Erk-1 levels were detected between 9 to 18 h post training but were absent at 24 h. These late increases were correlated with training strength. In rats that received a low electric shock (0,5 mA), sufficient to express memory 24 h later, increases in protein levels were not detected. However, when shock was increased (to 0,7 or 0,9 mA), latency to step down was significantly higher and biochemical changes were evident. It is interesting the fact that mRNA changes seem to be delayed respect to protein level changes. Moreover, c-fos and homer-1a are well known immediate early genes, having an unusual regulation of expression after IA learning. Some of the studied gene products were kinases that are known to be activated early after acquisition, such as CaMKIIa, Erk-2 and Akt. Given that IA memory appears to be fully consolidated 24 h after training, late protein synthesis in rat hippocampus might be necessary for memory maintenance, since biochemical changes correlate with higher and more perdurable memory expression.