A requirement for memory retrieval during and after long-term extinction learning
- Department of Pharmacology, University of Pennsylvania, 3620 Hamilton Walk, Philadelphia, PA 19104-6084
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Edited by Richard D. Palmiter, University of Washington School of Medicine, Seattle, WA (received for review March 21, 2005)
Abstract
Current learning theories are based on the idea that learning is driven by the difference between expectations and experience (the delta rule). In extinction, one learns that certain expectations no longer apply. Here, we test the potential validity of the delta rule by manipulating memory retrieval (and thus expectations) during extinction learning. Adrenergic signaling is critical for the time-limited retrieval (but not acquisition or consolidation) of contextual fear. Using genetic and pharmacologic approaches to manipulate adrenergic signaling, we find that long-term extinction requires memory retrieval but not conditioned responding. Identical manipulations of the adrenergic system that do not affect memory retrieval do not alter extinction. The results provide substantial support for the delta rule of learning theory. In addition, the timing over which extinction is sensitive to adrenergic manipulation suggests a model whereby memory retrieval occurs during, and several hours after, extinction learning to consolidate long-term extinction memory.
Footnotes
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↵ * To whom correspondence should be addressed. E-mail: thomas{at}pharm.med.upenn.edu.
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Author contributions: M.O. performed research; M.O. and S.A.T. analyzed data; S.A.T. designed research; and S.A.T. wrote the paper.
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This paper was submitted directly (Track II) to the PNAS office.
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Abbreviations: Aten, (-)-atenolol; CGP, CGP 20712A; CH, central hippocampus; CR, conditioned response; CS, conditioned stimulus; DH, dorsal hippocampus; E, epinephrine; ICV, intracerebroventricular; Iso, (±)-isoproterenol; L-DOPS, l-threo-3,4-dihydroxyphenylserine; NE, norepinephrine; Prop, (-)-propranolol; Sal, saline; US, unconditioned stimulus; Xam, xamoterol.
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See Commentary on page 9091.
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↵ † Robleto, K. & Thompson, R. F. (2004) Soc. Neurosci. Abstr. 30, 325.327 (abstr.).
- Copyright © 2005, The National Academy of Sciences
