A metaplasticity-like mechanism supports the selection of fear memories: role of protein kinase a in the amygdala.
How the brain determines which memories are selected for long-term storage is critical for a full understanding of memory. One possibility is that memories are selected based on the history of activity and current state of neurons within a given memory circuit. Many in vitro studies have demonstrated metaplasticity-like effects whereby prior neuronal activity can affect the ability of cells to express synaptic plasticity in the future; however, the significance of these findings to memory is less clear. Here we show in rats that a single pairing of a light with shock, insufficient to support either short- or long-term fear memory, primes future learning such that another trial delivered within a circumscribed time window lasting from ∼60 min to 3 d results in the formation of a long-lasting and robust fear memory. Two adequately spaced training trials support long-term fear memory only if the two trials are signaled by the same cue. Furthermore, although a single training trial does not support formation of an observable fear memory, it does result in the phosphorylation of several targets of protein kinase A (PKA) in the amygdala. Accordingly, blocking PKA signaling in the amygdala before the first training trial completely prevents the ability of that trial to facilitate the formation of long-term fear memory when a second trial is delivered 24 h later. These findings may provide insight into how memories are selected for long-term storage.
Department of Psychiatry and Behavioral Sciences, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia 30329, USA. rparso3@emory.edu
Ryan G
RG
Parsons
Michael
M
Davis
D000679:Amygdala / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001522:Behavior, Animal; D015153:Blotting, Western; D003463:Cues; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D004597:Electroshock; D005239:Fear / Q000187:drug effects / Q000502:physiology* / Q000523:psychology*; D007858:Learning / Q000502:physiology; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D057567:Memory, Long-Term / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects / Q000502:physiology; D013873:Thionucleotides / Q000494:pharmacology
D047428:Protein Kinase Inhibitors; D013873:Thionucleotides; C015929:8-((4-chlorophenyl)thio)cyclic-3',5'-AMP; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases