Temporal factors control hippocampal contributions to fear renewal after extinction
Article first published online: 26 MAY 2011
Copyright © 2011 Wiley Periodicals, Inc.
Special Issue: Proteins and Proteomics
Volume 22, Issue 5, pages 1096–1106, May 2012
How to Cite
Zelikowsky, M., Pham, D. L. and Fanselow, M. S. (2012), Temporal factors control hippocampal contributions to fear renewal after extinction. Hippocampus, 22: 1096–1106. doi: 10.1002/hipo.20954
- Issue published online: 14 APR 2012
- Article first published online: 26 MAY 2011
- Manuscript Accepted: 4 MAR 2011
- National Institute of Mental Health. Grant Number: RO1MH062122
- University of California, Los Angeles Cota Robles Fellowship
- fear conditioning;
Fear can be extinguished by repeated exposure to a cue that signals threat. However, extinction does not erase fear, as an extinguished cue presented in a context distinct from that of extinction results in renewed fear of that cue. The hippocampus, which is involved in the formation of contextual representations, is a natural candidate structure for investigations into the neural circuitry underlying fear renewal. Thus far, studies examining the necessity of the hippocampus for fear renewal have produced mixed results. We isolated the conditions under which the hippocampus may be required for renewal. Rats received lesions of the dorsal hippocampus either prior to tone fear conditioning or following extinction. Fear renewal was measured using discrete tone presentations or a long, continuous tone. The topography of fear responding at test was assessed by comparing “early” and “sustained” renewal, where early fear was determined by freezing to the first discrete tone or the equivalent initial segment of a continuous tone and sustained fear was determined by freezing averaged across all discrete tones or the entire continuous tone. We found that following pretraining damage of the hippocampus, early renewal remained intact regardless of lesion condition. However, sustained renewal only persisted in discrete, but not continuous, tone-tested animals. A more extensive analysis of the topography of fear responding revealed that the disruption of renewal was generated when the tone duration at test began to violate that used during extinction, suggesting that the hippocampus is sensitive to mismatches in CS-duration. Postextinction lesions resulted in an overall reduction of fear renewal. This pattern of results is consistent with those observed for contextual fear conditioning, wherein animals display a resistance to anterograde amnesia despite the presence of a strong retrograde amnesia for the same contextual information. Furthermore, the data support a role for the hippocampus in sustaining renewal when the CS duration at test does not match that used during extinction. © 2011 Wiley Periodicals, Inc.