Inactivation of the anterior cingulate reveals enhanced reliance on cortical networks for remote spatial memory retrieval after sequential memory processing

PLoS One. 2014 Oct 3;9(10):e108711. doi: 10.1371/journal.pone.0108711. eCollection 2014.

Abstract

One system consolidation model suggests that as time passes, ensembles of cortical neurons form strong connections to represent remote memories. In this model, the anterior cingulate cortex (ACC) serves as a cortical region that represents remote memories. However, there is debate as to whether remote spatial memories go through this systems consolidation process and come to rely on the ACC. The present experiment examined whether increasing the processing demand on the hippocampus, by sequential training on two spatial tasks, would more fully engage the ACC during retrieval of a remote spatial memory. In this scenario, inactivation of the ACC at a remote time point was hypothesized to produce a severe memory deficit if rats had been trained on two, sequential spatial tasks. Rats were trained on a water maze (WM) task only or a WM task followed by a radial arm maze task. A WM probe test was given recently or remotely to all rats. Prior to the probe test, rats received an injection of saline or muscimol into the ACC. A subtle deficit in probe performance was found at the remote time point in the group trained on only one spatial task and treated with muscimol. In the group trained on two spatial tasks and treated with muscimol, a subtle deficit in probe performance was noted at the recent time point and a substantial deficit in probe performance was observed at the remote time point. c-Fos labeling in the hippocampus revealed more labeling in the CA1 region in all remotely tested groups than recently tested groups. Findings suggest that spatial remote memories come to rely more fully on the ACC when hippocampal processing requirements are increased. Results also suggest continued involvement of the hippocampus in spatial memory retrieval along with a progressive strengthening of cortical connections as time progresses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • GABA-A Receptor Agonists / pharmacology
  • Gyrus Cinguli / drug effects
  • Gyrus Cinguli / physiology*
  • Male
  • Maze Learning / drug effects
  • Maze Learning / physiology*
  • Memory, Long-Term / drug effects
  • Memory, Long-Term / physiology*
  • Muscimol / pharmacology
  • Rats
  • Rats, Long-Evans
  • Space Perception / drug effects
  • Space Perception / physiology
  • Spatial Memory / drug effects
  • Spatial Memory / physiology*

Substances

  • GABA-A Receptor Agonists
  • Muscimol

Grants and funding

This research was supported by National Science and Engineering Research Council of Canada Discovery grants to MRH (RGPIN 341673) and a Canadian Foundation for Innovation grant (335892) to MRH. BCW was supported by an Alexander Graham Bell Post-Graduate Scholarship from the National Science and Engineering Research Council of Canada. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.