title: Mechanisms underlying long-term fear memory formation from a metaplastic neuronal state.
abstract: We previously showed that a single weak fear conditioning trial, that does not produce a long-term fear memory (LTM), appeared to prime memory formation such that when a second trial followed within a circumscribed time window a robust and long-lasting fear memory was formed. We also showed that this priming effect could be blocked if we interfered with protein kinase A (PKA) signaling in the amygdala during the first conditioning trial. The goals of the current study were to determine if LTM formation after the second trial depends on PKA signaling in the amygdala and to characterize the underlying memory processes engaged during the second trial that allows for LTM formation. Our interpretation of the original findings is that the second conditioning trial triggers LTM from a metaplastic state that is engaged by the first conditioning trial. However, it is also possible that the second conditioning trial acts as a reminder of the first and engages a reconsolidation-like process. Several experiments were conducted to distinguish between these two possibilities. We show that interfering with PKA signaling during the second conditioning trial disrupts memory formation. However, if a third trial follows the second or if the second trial was presented without shock, the PKA inhibitor was no longer effective. Our findings demonstrate that the induction of fear memory from a metaplastic state involves new learning that is distinct from retrieval-dependent updating of memories.
authors.affiliation: Emory University, Department of Psychiatry and Behavioral Sciences, United States; Stony Brook University, Department of Psychology and Neurosciences Institute, United States. Electronic address: ryan.parsons@stonybrook.edu.
authors.forename: Ryan G
authors.initials: RG
authors.lastname: Parsons
authors.affiliation: Emory University, Department of Psychiatry and Behavioral Sciences, United States.
authors.forename: David L
authors.initials: DL
authors.lastname: Walker
authors.affiliation: Emory University, Department of Psychiatry and Behavioral Sciences, United States.
authors.forename: Michael
authors.initials: M
authors.lastname: Davis
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005239:Fear / Q000187:drug effects / Q000502:physiology*; D008297:Male; D000069077:Memory Consolidation / Q000187:drug effects / Q000502:physiology*; D057567:Memory, Long-Term / Q000187:drug effects / Q000502:physiology*; D011939:Mental Recall / Q000187:drug effects / Q000502:physiology*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013873:Thionucleotides / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D013873:Thionucleotides; C015929:8-((4-chlorophenyl)thio)cyclic-3',5'-AMP; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases
keywords: Amygdala; Consolidation; Fear; Memory; Metaplasticity; Retrieval