Tonic activity in lateral habenula neurons acts as a neutral valence brake on reward-seeking behavior

Curr Biol. 2022 Oct 24;32(20):4325-4336.e5. doi: 10.1016/j.cub.2022.08.016. Epub 2022 Aug 31.

Abstract

Survival requires both the ability to persistently pursue goals and the ability to determine when it is time to stop, an adaptive balance of perseverance and disengagement. Neural activity in the lateral habenula (LHb) has been linked to negative valence, but its role in regulating the balance between engaged reward seeking and disengaged behavioral states remains unclear. Here, we show that LHb neural activity is tonically elevated during minutes-long periods of disengagement from reward-seeking behavior, both when due to repeated reward omission (negative valence) and when sufficient reward has been consumed (positive valence). Furthermore, we show that LHb inhibition extends ongoing reward-seeking behavioral states but does not prompt task re-engagement. We find no evidence for similar tonic activity changes in ventral tegmental area dopamine neurons. Our findings support a framework in which tonic activity in LHb neurons suppresses engagement in reward-seeking behavior in response to both negatively and positively valenced factors.

Keywords: behavioral state; calcium imaging; disengagement; dopamine; lateral habenula; motivated behavior; reward; tonic activity; valence; ventral tegmental area.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dopaminergic Neurons / physiology
  • Electric Stimulation
  • Habenula* / physiology
  • Neural Pathways / physiology
  • Reward
  • Ventral Tegmental Area / physiology