Increased histone acetyltransferase and lysine acetyltransferase activity and biphasic activation of the ERK/RSK cascade in insular cortex during novel taste learning

Changes in gene expression are thought to be involved in neuronal plasticit y associated with learning and memory. Although acetylation of lysine resid ues on histones by histone acetyltransferases (HAT) is an obligatory compon ent of transcription, HAT activity has been largely ignored in studies of t he nervous system. We developed a new model for studying novel taste learni ng using novel solid food presentation to nondeprived animals. Using this b ehavioral paradigm, we investigated short- and long-term regulation of lysi ne acetyltransferase activity and the ERK/mitogen-activated protein kinase (MAPK)/RSK cascade in insular cortex, a CNS region known to be crucial for the formation of novel taste memories. We observed that novel taste learnin g elicited biphasic (acute and long-lasting) activation of two distinct lys ine acetyltransferase activities along with the ERK/MAPK cascade in insular cortex. In vitro studies revealed that the ERK cascade could regulate the lysine acetylation of a 42 kDa lysine acetyltransferase substrate, suggesti ng a causal relationship between ERK activation and lysine acetyltransferas e activity in insular cortex. Overall, our studies reveal an unanticipated long-lasting activation of insular cortex signal transduction cascades in n ovel taste learning. Furthermore, our studies suggest the hypothesis that a cute and long-term ERK activation and lysine-histone acetyltransferase acti vation may play a role in regulating gene expression in single-trial learni ng and long-term memory formation.