NEWS AND VIEWS Figure 1 Simplified illustration of the Phase 1:awake conditioning in scanner experimental protocol.In phase 1,two faces (face 1 and face 3)were presented without being Target odor Non-target odor paired with shock and two other faces (face 2 and face 4)were paired with shock.Face 1 (the target CS-)and face 2 (the target CS+)were presented in the presence of one odor(the target odor,here ace 2 Face 3: Face 4: oranges),and face 3(the non-target CS-)and face 4(the non-target CS+)were presented in the presence of a different odor (the non-target odor, here pine).After having been paired with shock, both face 2 and face 4 elicited fear (indicated by an elevated skin-conductance response).In Target CS Non-target CS- Non-target CS+ phase 2,the subject napped and the target odor was re-exposed during slow-wave sleep in 30-s on-off cycles.Finally,in phase 3,the faces were presented again.Face 2 (the target CS+)then elicited less fear than face 4(the non-target CS+). REM,rapid eye motion sleep. re-exposed.Presumably,no competing mem- ories were formed when context re-exposure occurred during slow-wave sleep (and probably not when animals were re-exposed to a famil- Phase 2:target odorant context re-exposure during sleep sy6u iar context in earlier studies either).In con- trast,awake subjects in Hauner et al.viewed a nature-themed documentary film during odorant context re-exposure.Memory for the documentary film was not subsequently tested, but it seems likely that,had it been tested,the subjects would have remembered much of Stage Stage 2 Slow-wave sleep REM what they had seen in the film.The encoding of these film-related memories during odor- ant context re-exposure undoubtedly activated Phase 3:awake testing in scanner hippocampal encoding and consolidation pro- cesses that could interfere with other memo- Target odor Non-target odor 8100 ries formed around the same time.Thus,for T FEAR O the awake controls,film-related memories may have competed with the consolidation of any Face 1: Face 3: F3084 CS+memories that were concomitantly cued by the presentation of the odorant context (perhaps preventing consolidation of memory for a safe version of that stimulus). In studies using rats,a distinction is often drawn between active wake versus quiet wake Target CS- Target CS+ Non-target CS- Non-target CS+ In Buzsaki's two-stage model ofencoding and consolidationo,for example,active wake (such as exploration of a novel environment) is associated with encoding activity,whereas quiet wake is associated with the consolida- tion of recently formed memories (perhaps via neural replay,which occurs not only dur- ing slow-wave sleep,but also during quiet wakell).Presumably,humans watching a re-exposure-memories that might otherwise be considerably greater if it were possible to nature-themed documentary film are not in have been consolidated if a state of quiet wake achieve in the awake state.Context stimuli a state of quiet wake,but are instead in a state had been in effect instead12.13.Indeed,inother often consist of visual cues,such as when a that is more akin to rats exploring a novel envi- kinds oflearning tasks,post-learning wakeful PTSD patient acquires an exaggerated fear of ronment(that is,in a state that is more akin to resting has yielded effects on the consolidation driving in close proximity to a truck following active wake).If so,the encoding of extrane- of memory not unlike the effects associated a serious motor vehicle accident.Obviously. ous memories that will inevitably occur dur- with slow-wave sleep4.15. visual context cues cannot be conveniently ing active wake may serve to interfere with The potential therapeutic benefit of extin- presented during sleep,but the results reported recently formed (and,therefore,still labile) guishing a feared CS without having to pre- by Hauner et als raise the possibility that memories of the safe CS+cued by context sent the CS itself is considerable and would context re-exposure during quiet wake may NATURE NEUROSCIENCE VOLUME 16 NUMBER 11I NOVEMBER 2013 1511nature neuroscience volume 16 | number 11 | NOVEMber 2013 1511 news and views be considerably greater if it were possible to achieve in the awake state. Context stimuli often consist of visual cues, such as when a PTSD patient acquires an exaggerated fear of driving in close proximity to a truck following a serious motor vehicle accident. Obviously, visual context cues cannot be conveniently presented during sleep, but the results reported by Hauner et al.5 raise the possibility that context re-exposure during quiet wake may re-exposed. Presumably, no competing mem￾ories were formed when context re-exposure occurred during slow-wave sleep (and probably not when animals were re-exposed to a famil￾iar context in earlier studies either). In con￾trast, awake subjects in Hauner et al.5 viewed a nature-themed documentary film during odorant context re-exposure. Memory for the documentary film was not subsequently tested, but it seems likely that, had it been tested, the subjects would have remembered much of what they had seen in the film. The encoding of these film-related memories during odor￾ant context re-exposure undoubtedly activated hippocampal encoding and consolidation pro￾cesses that could interfere with other memo￾ries formed around the same time9. Thus, for the awake controls, film-related memories may have competed with the consolidation of any CS+ memories that were concomitantly cued by the presentation of the odorant context (perhaps preventing consolidation of memory for a safe version of that stimulus). In studies using rats, a distinction is often drawn between active wake versus quiet wake. In Buzsáki’s two-stage model of encoding and consolidation10, for example, active wake (such as exploration of a novel environment) is associated with encoding activity, whereas quiet wake is associated with the consolida￾tion of recently formed memories (perhaps via neural replay, which occurs not only dur￾ing slow-wave sleep, but also during quiet wake11). Presumably, humans watching a nature-themed documentary film are not in a state of quiet wake, but are instead in a state that is more akin to rats exploring a novel envi￾ronment (that is, in a state that is more akin to active wake). If so, the encoding of extrane￾ous memories that will inevitably occur dur￾ing active wake may serve to interfere with recently formed (and, therefore, still labile) memories of the safe CS+ cued by context re-exposure—memories that might otherwise have been consolidated if a state of quiet wake had been in effect instead12,13. Indeed, in other kinds of learning tasks, post-learning wakeful resting has yielded effects on the consolidation of memory not unlike the effects associated with slow-wave sleep14,15. The potential therapeutic benefit of extin￾guishing a feared CS without having to pre￾sent the CS itself is considerable and would Marina Corral Spence Figure 1 Simplified illustration of the experimental protocol. In phase 1, two faces (face 1 and face 3) were presented without being paired with shock and two other faces (face 2 and face 4) were paired with shock. Face 1 (the target CS–) and face 2 (the target CS+) were presented in the presence of one odor (the target odor, here oranges), and face 3 (the non-target CS–) and face 4 (the non-target CS+) were presented in the presence of a different odor (the non-target odor, here pine). After having been paired with shock, both face 2 and face 4 elicited fear (indicated by an elevated skin-conductance response). In phase 2, the subject napped and the target odor was re-exposed during slow-wave sleep in 30-s on-off cycles. Finally, in phase 3, the faces were presented again. Face 2 (the target CS+) then elicited less fear than face 4 (the non-target CS+). REM, rapid eye motion sleep. FEAR FEAR FEAR FEAR Phase 1: awake conditioning in scanner Phase 2: target odorant context re-exposure during sleep Target CS– Target CS+ Non-target CS– Non-target CS+ Target odor Non-target odor Stage 1 Stage 2 Slow-wave sleep REM Face 1: Face 2: Face 3: Face 4: Target CS– Target CS+ Non-target CS– Non-target CS+ Face 1: Face 2: Face 3: Face 4: Phase 3: awake testing in scanner Target odor Non-target odor npg © 2013 Nature America, Inc. All rights reserved