Context-dependent modulation of hippocampal and cortical recruitment during remote spatial memory retrieval

Hippocampus. 2012 Apr;22(4):827-41. doi: 10.1002/hipo.20943. Epub 2011 May 3.


According to systems consolidation, as hippocampal-dependent memories mature over time, they become additionally (or exclusively) dependent on extra-hippocampal structures. We assessed the recruitment of hippocampal and cortical structures on remote memory retrieval in a performance-degradation resistant (PDR; no performance degradation with time) versus performance-degradation prone (PDP; performance degraded with time) context. Using a water-maze task in two contexts with a hidden platform and three control conditions (home cage, visible platform with or without access to distal cues), we compared neuronal activation (c-Fos imaging) patterns in the dorsal hippocampus and the medial prefrontal cortex (mPFC) after the retrieval of recent (5 days) versus remote (25 days) spatial memory. In the PDR context, the hippocampus exhibited greater c-Fos protein expression on remote than recent memory retrieval, be it in the visible or hidden platform group. In the PDP context, hippocampal activation increased at the remote time point and only in the hidden platform group. In the anterior cingulate cortex, c-Fos expression was greater for remote than for recent memory retrieval and only in the PDR context. The necessity of the mPFC for remote memory retrieval in the PDR context was confirmed using region-specific lidocaine inactivation, which had no impact on recent memory. Conversely, inactivation of the dorsal hippocampus impaired both recent and remote memory in the PDR context, and only recent memory in the PDP context, in which remote memory performance was degraded. While confirming that neuronal circuits supporting spatial memory consolidation are reorganized in a time-dependent manner, our findings further indicate that mPFC and hippocampus recruitment (i) depends on the content and perhaps the strength of the memory and (ii) may be influenced by the environmental conditions (e.g., cue saliency, complexity) in which memories are initially formed and subsequently recalled.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Hippocampus / drug effects
  • Hippocampus / physiology*
  • Lidocaine / administration & dosage
  • Male
  • Maze Learning / physiology
  • Memory, Long-Term / drug effects
  • Memory, Long-Term / physiology*
  • Mental Recall / physiology
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / physiology*
  • Proto-Oncogene Proteins c-fos / metabolism
  • Rats
  • Rats, Long-Evans
  • Recruitment, Neurophysiological / physiology
  • Time Factors


  • Proto-Oncogene Proteins c-fos
  • Lidocaine