A distinct role for norepinephrine in memory retrieval.
A role for norepinephrine in learning and memory has been elusive and controversial. A longstanding hypothesis states that the adrenergic nervous system mediates enhanced memory consolidation of emotional events. We tested this hypothesis in several learning tasks using mutant mice conditionally lacking norepinephrine and epinephrine, as well as control mice and rats treated with adrenergic receptor agonists and antagonists. We find that adrenergic signaling is critical for the retrieval of intermediate-term contextual and spatial memories, but is not necessary for the retrieval or consolidation of emotional memories in general. The role of norepinephrine in retrieval requires signaling through the beta(1)-adrenergic receptor in the hippocampus. The results demonstrate that mechanisms of memory retrieval can vary over time and can be different from those required for acquisition or consolidation. These findings may be relevant to symptoms in several neuropsychiatric disorders as well as the treatment of cardiac failure with beta blockers.
Murchison
Charles F
CF
Department of Pharmacology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Zhang
Xiao-Yan
XY
Zhang
Wei-Ping
WP
Ouyang
Ming
M
Lee
Anee
A
Thomas
Steven A
SA
D000322:Adrenergic Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000009:adverse effects; D000818:Animals; D003214:Conditioning, Classical; D004305:Dose-Response Relationship, Drug; D004644:Emotions / Q000502:physiology; D004837:Epinephrine / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D008569:Memory Disorders / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D013028:Space Perception / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology*
D000322:Adrenergic Agonists; D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; D009638:Norepinephrine; D004837:Epinephrine