CNO was obtained from the NIH as part of the Rapid Access to Investigative Drug Program funded by the NINDS. This work was supported
by grants from “Anonymous Foundation” and NARSAD to C.K., from the International Mental Health Research Organization, the Hope for Depression Research Foundation, and the NIH (R21 MH093887 and R01 MH081968) to J.A.G, U19MH82441 to B.L.R., and a Fondation Fyssen Fellowship to S.P. A.I.A. is a Leon Levy Foundation Resident Fellow and is supported by R25 MH086466. S.P. designed and performed the experiments, conducted the data analysis, and wrote the paper. P.K.O. performed the in vivo recordings experiment and conducted the analysis. S.S.B. and R.D.W. helped with behavior experiments. A.I.A. assisted in the analysis of the in vivo recordings. B.L.R. provided the DREADD system. P.B. supervised and designed behavioral IOX1 concentration experiments. J.A.G. and C.K. designed and supervised the performance of the experiments and data analysis and wrote the paper. “
“New experiences are accompanied by profound increases in the level of coordinated
memory reactivation in the hippocampus during sharp-wave ripple (SWR) events (Foster and Wilson, 2006; Cheng and Frank, 2008; Karlsson and Frank, 2008; O’Neill et al., 2008). These reactivation events frequently replay entire behavioral trajectories representing either past or possible future locations (Foster and Wilson, 2006; Diba and Buzsáki, 2007; Davidson et al., 2009; Karlsson and Frank, 2009; Gupta et al., 2010) and reactivation strength during and after an experience correlates with subsequent memory (Nakashiba selleck screening library et al., 2009; Dupret et al., 2010). Disrupting SWRs during sleep leads to subsequent performance deficits in a spatial memory task (Girardeau et al., 2009; Ego-Stengel and Wilson, 2010), and disrupting SWRs during behavior causes performance
deficits in a spatial learning task (Jadhav et al., 2012). While these findings have established the importance of SWRs for learning, it is unclear how SWR activity contributes to memory-guided behavior. We have hypothesized that SWR reactivation represents recent and possible future paths to aid ongoing memory-guided navigation (Karlsson and Frank, 2009; almost Carr et al., 2011). However, to date no one has examined whether reactivation during learning is related to choice behavior in a hippocampally dependent spatial task. We asked how SWR reactivation could aid memory-guided decisions in animals learning a W-track alternation task in initially novel environments (Frank et al., 2000; Karlsson and Frank, 2008; Kim and Frank, 2009). We focused on the outbound, SWR-dependent component of the task (Jadhav et al., 2012). On outbound trials, animals begin in the center arm of the track. Correct performance of the task is to alternate between outside arms. To accomplish this, animals must remember which outside arm they visited most recently and choose a path to the opposite arm.