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 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.
Swank
M W
MW
Division of Neuroscience, Baylor College of Medicine, Houston, Texas 77030, USA. mswank@cns.bcm.tmc.edu
Sweatt
J D
JD
D000107:Acetylation / Q000187:drug effects; D000123:Acetyltransferases / Q000378:metabolism*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D002540:Cerebral Cortex / Q000737:chemistry / Q000201:enzymology*; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D004193:Discrimination Learning / Q000187:drug effects / Q000502:physiology*; D004435:Eating / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051548:Histone Acetyltransferases; D056572:Histone Deacetylase Inhibitors; D066298:In Vitro Techniques; D018021:Lithium Chloride / Q000494:pharmacology; D008239:Lysine / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011494:Protein Kinases / Q000378:metabolism; D019893:Ribosomal Protein S6 Kinases; D029701:Saccharomyces cerevisiae Proteins; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013649:Taste / Q000502:physiology*
D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D029701:Saccharomyces cerevisiae Proteins; D000123:Acetyltransferases; D051548:Histone Acetyltransferases; D011494:Protein Kinases; D019893:Ribosomal Protein S6 Kinases; D020928:Mitogen-Activated Protein Kinases; D018021:Lithium Chloride; D008239:Lysine