Redundant catecholamine signaling consolidates fear memory via phospholipase C.
Memories for emotionally arousing experiences are typically vivid and persistent. The recurrent, intrusive memories of traumatic events in post-traumatic stress disorder (PTSD) are an extreme example. Stress-responsive neurotransmitters released during emotional arousal are proposed to enhance the consolidation of fear memory. These transmitters may include norepinephrine and epinephrine (NE/E) because stimulating β-adrenergic receptors shortly after training can enhance memory consolidation. However, mice lacking NE/E acquire and consolidate fear memory normally. Here, we show by using pharmacologic and genetic manipulations in mice and rats that NE/E are not essential for classical fear memory consolidation because signaling by the β(2)-adrenergic receptor is redundant with signaling by dopamine at the D(5)-dopaminergic receptor. The intracellular signaling that is stimulated by these receptors to promote consolidation uses distinct G proteins to redundantly activate phospholipase C. The results support recent evidence indicating that blocking β-adrenergic receptors alone shortly after trauma may not be sufficient to prevent PTSD.
Department of Pharmacology and Neuroscience Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6084, USA.
Ming
M
Ouyang
Matthew B
MB
Young
Melissa M
MM
Lestini
Keith
K
Schutsky
Steven A
SA
Thomas
D000818:Animals; D001930:Brain Injuries / Q000201:enzymology / Q000378:metabolism / Q000523:psychology; D004298:Dopamine / Q000502:physiology; D004837:Epinephrine / Q000172:deficiency / Q000502:physiology*; D005239:Fear / Q000502:physiology* / Q000523:psychology; D005260:Female; D008568:Memory / Q000502:physiology*; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009638:Norepinephrine / Q000172:deficiency / Q000502:physiology*; D051381:Rats; D011916:Rats, Inbred F344; D018343:Receptors, Adrenergic, beta-2 / Q000502:physiology; D050641:Receptors, Dopamine D5 / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D010738:Type C Phospholipases / Q000502:physiology*
D018343:Receptors, Adrenergic, beta-2; D050641:Receptors, Dopamine D5; D010738:Type C Phospholipases; D004298:Dopamine; D009638:Norepinephrine; D004837:Epinephrine