, P.B.), and the Lipper Family Foundation (C.F.C.). None of ISRIB mouse the authors of this manuscript have a financial interest related to this work. “
“It is widely accepted that there are at least three stages in the life of a memory: encoding, retrieval, and consolidation. There has been a wealth of cognitive neuroscience research in the last decade focused on revealing the mechanisms by which the medial temporal lobe (MTL) creates, or encodes, a lasting trace of our experience so that we can later retrieve it. A number of recent reviews describe our current knowledge with respect to the roles of distinct MTL subregions in memory encoding and retrieval (Davachi, 2006, Eichenbaum et al., 2007, Diana et al., 2007 and Squire

et al., 2007). In sum, there is growing evidence from both animal and human research that the perirhinal cortex is important

in the encoding of individual items or objects from an experience, while the hippocampus is important for linking distinct item representations in memory (Davachi et al., 2003, Staresina and Davachi, 2009, Ranganath et al., 2004, Tubridy and Davachi, 2011 and Brown and Aggleton, 2001). Further, the perirhinal cortex also appears to contribute to some forms of associative encoding. Recent fMRI work has shown that blood oxygenation level-dependent (BOLD) activation in the perirhinal cortex is related to item encoding as well as the associative encoding Neratinib of item features, but not extra-item episodic details else (Staresina and Davachi, 2008 and Staresina et al., 2011). However, little is known about how MTL structures interact to support memory consolidation. Systems-level memory consolidation is typically conceptualized as the process by which initially hippocampal-dependent memories become less reliant on the hippocampus and become more widely supported by cortical regions. This shift, or distribution of the memory trace, is thought to provide resistance to local damage and confer

a resistance to forgetting (see Wixted, 2004). One emerging mechanism hypothesized to support memory consolidation is hippocampal-mediated replay or reactivation. Replay has been defined as the reactivation of brain activity characteristic of a prior experience during postencoding time periods (Buzsáki, 1989, Stickgold et al., 2001 and Marr, 1971; see also Káli and Dayan, 2004). Thus far, evidence in support of this proposal has emerged primarily from animal electrophysiological studies demonstrating that hippocampal neural firing patterns associated with maze running and learning are subsequently replayed during sleep and awake rest (e.g., Skaggs and McNaughton, 1996, Qin et al., 1997, Wilson and McNaughton, 1994, Ji and Wilson, 2007 and Karlsson and Frank, 2009). Furthermore, disruption of neural signatures of replay (i.e., sharp-wave ripples) has been shown to impair learning, providing a causal link between memory consolidation and neural replay (Ego-Stengel and Wilson, 2010 and Jadhav et al., 2012).