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The Journal of Neuroscience, May 15, 2001, 21(10):3383-3391

Increased Histone Acetyltransferase and Lysine Acetyltransferase Activity and Biphasic Activation of the ERK/RSK Cascade in Insular Cortex During Novel Taste Learning

Michael W. Swank and J. David Sweatt

Division of Neuroscience, Baylor College of Medicine, Houston, Texas 77030

Changes in gene expression are thought to be involved in neuronal plasticity associated with learning and memory. Although acetylation of lysine residues on histones by histone acetyltransferases (HAT) is an obligatory component of transcription, HAT activity has been largely ignored in studies of the nervous system. We developed a new model for studying novel taste learning using novel solid food presentation to nondeprived animals. Using this behavioral paradigm, we investigated short- and long-term regulation of lysine 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 learning elicited biphasic (acute and long-lasting) activation of two distinct lysine 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, suggesting a causal relationship between ERK activation and lysine acetyltransferase activity in insular cortex. Overall, our studies reveal an unanticipated long-lasting activation of insular cortex signal transduction cascades in novel taste learning. Furthermore, our studies suggest the hypothesis that acute and long-term ERK activation and lysine-histone acetyltransferase activation may play a role in regulating gene expression in single-trial learning and long-term memory formation.

Key words: MAP kinase; histone acetyltransferase; protein kinase; taste aversion; insular cortex; learning; memory; gene expression

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Copyright © 2001 Society for Neuroscience  0270-6474/01/21103383-09$05.00/0

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