Artificial theta stimulation impairs encoding of contextual fear memory

PLoS One. 2012;7(11):e48506. doi: 10.1371/journal.pone.0048506. Epub 2012 Nov 1.

Abstract

Several experiments have demonstrated an intimate relationship between hippocampal theta rhythm (4-12 Hz) and memory. Lesioning the medial septum or fimbria-fornix, a fiber track connecting the hippocampus and the medial septum, abolishes the theta rhythm and results in a severe impairment in declarative memory. To assess whether there is a causal relationship between hippocampal theta and memory formation we investigated whether restoration of hippocampal theta by electrical stimulation during the encoding phase also restores fimbria-fornix lesion induced memory deficit in rats in the fear conditioning paradigm. Male Wistar rats underwent sham or fimbria-fornix lesion operation. Stimulation electrodes were implanted in the ventral hippocampal commissure and recording electrodes in the septal hippocampus. Artificial theta stimulation of 8 Hz was delivered during 3-min free exploration of the test cage in half of the rats before aversive conditioning with three foot shocks during 2 min. Memory was assessed by total freezing time in the same environment 24 h and 28 h after fear conditioning, and in an intervening test session in a different context. As expected, fimbria-fornix lesion impaired fear memory and dramatically attenuated hippocampal theta power. Artificial theta stimulation produced continuous theta oscillations that were almost similar to endogenous theta rhythm in amplitude and frequency. However, contrary to our predictions, artificial theta stimulation impaired conditioned fear response in both sham and fimbria-fornix lesioned animals. These data suggest that restoration of theta oscillation per se is not sufficient to support memory encoding after fimbria-fornix lesion and that universal theta oscillation in the hippocampus with a fixed frequency may actually impair memory.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amygdala / physiology
  • Animals
  • Brain Mapping / methods
  • Conditioning, Psychological
  • Electrodes
  • Electroencephalography / methods
  • Fear*
  • Hippocampus / physiology
  • Immunohistochemistry / methods
  • Male
  • Maze Learning
  • Memory / physiology*
  • Oscillometry / methods
  • Rats
  • Rats, Wistar
  • Theta Rhythm / physiology*
  • Time Factors

Grants and funding

The study was supported by the Emil Aaltonen Foundation (personal grant AJL). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.