Electrical stimulation of lateral habenula during learning: frequency-dependent effects on acquisition but not retrieval of a two-way active avoidance response

PLoS One. 2013 Jun 28;8(6):e65684. doi: 10.1371/journal.pone.0065684. Print 2013.


The lateral habenula (LHb) is an epithalamic structure involved in signaling reward omission and aversive stimuli, and it inhibits dopaminergic neurons during motivated behavior. Less is known about LHb involvement in the acquisition and retrieval of avoidance learning. Our previous studies indicated that brief electrical stimulation of the LHb, time-locked to the avoidance of aversive footshock (presumably during the positive affective "relief" state that occurs when an aversive outcome is averted), inhibited the acquisition of avoidance learning. In the present study, we used the same paradigm to investigate different frequencies of LHb stimulation. The effect of 20 Hz vs. 50 Hz vs. 100 Hz stimulation was investigated during two phases, either during acquisition or retrieval in Mongolian gerbils. The results indicated that 50 Hz, but not 20 Hz, was sufficient to produce a long-term impairment in avoidance learning, and was somewhat more effective than 100 Hz in this regard. None of the stimulation parameters led to any effects on retrieval of avoidance learning, nor did they affect general motor activity. This suggests that, at frequencies in excess of the observed tonic firing rates of LHb neurons (>1-20 Hz), LHb stimulation may serve to interrupt the consolidation of new avoidance memories. However, these stimulation parameters are not capable of modifying avoidance memories that have already undergone extensive consolidation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Avoidance Learning / physiology*
  • Electric Stimulation
  • Electrodes, Implanted
  • Gerbillinae
  • Habenula / physiology*
  • Male
  • Motor Activity
  • Reward

Grants and funding

The study was supported by grants from the Deutsche Forschungsgemeinschaft DFG (SFB 779, SFB-TRR-62) and from the Center for Behavioral Brain Research (CBBS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.