Regulation of synaptic plasticity genes during consolidation of fear conditioning.
In mammals, long-term memory induced by Pavlovian fear conditioning has been shown to be dependent on the amygdala during a protein and mRNA synthesis-dependent phase of memory consolidation. We have used genes identified in a kainic acid model of synaptic plasticity as in situ hybridization probes during the consolidation period after fear conditioning. We found that these genes were transcriptionally regulated in several brain areas only when stimuli were presented in a manner that supported behavioral learning and not after unpaired presentations or footshocks alone. Immediate early genes and neurofilament mRNA peaked approximately 30 min after conditioning, as expected. Interestingly, nurr-1, alpha-actinin, and 16c8 increased approximately 2-4 hr later, whereas neurogranin and gephyrin decreased during that time. Our results suggest that fear memory consolidation occurs within a broad neural circuit that includes, but is not limited to, the amygdala. Together, a broad array of transcriptionally regulated genes, encoding transcription factors, cytoskeletal proteins, adhesion molecules, and receptor stabilization molecules, appear to mediate the neural plasticity underlying specific forms of long-term memory in mammals.
Ressler
Kerry J
KJ
Department of Psychiatry and Behavioral Sciences, Center for Behavioral Neuroscience, Emory University School of Medicine, Atlanta, Georgia 30322, USA. kressle@emory.edu
Paschall
Gayla
G
Zhou
Xiao-liu
XL
Davis
Michael
M
D000818:Animals; D001245:Association Learning / Q000502:physiology; D001522:Behavior, Animal / Q000502:physiology; D001921:Brain / Q000378:metabolism; D002148:Calmodulin-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D003214:Conditioning, Classical / Q000502:physiology*; D004597:Electroshock; D005239:Fear / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D017781:Genes, Immediate-Early / Q000502:physiology; D017403:In Situ Hybridization; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008568:Memory / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D016900:Neurofilament Proteins / Q000235:genetics / Q000378:metabolism; D051579:Neurogranin; D009473:Neuronal Plasticity / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D009812:Odorants; D009928:Organ Specificity; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000502:physiology
D002148:Calmodulin-Binding Proteins; D002352:Carrier Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D016900:Neurofilament Proteins; C496651:Nrgn protein, rat; D012333:RNA, Messenger; C073441:gephyrin; D051579:Neurogranin; D007608:Kainic Acid