Three Rostromedial Tegmental Afferents Drive Triply Dissociable Aspects of Punishment Learning and Aversive Valence Encoding

Neuron. 2019 Dec 4;104(5):987-999.e4. doi: 10.1016/j.neuron.2019.08.040. Epub 2019 Oct 15.


Persistence of reward seeking despite punishment or other negative consequences is a defining feature of mania and addiction, and numerous brain regions have been implicated in such punishment learning, but in disparate ways that are difficult to reconcile. We now show that the ability of an aversive punisher to inhibit reward seeking depends on coordinated activity of three distinct afferents to the rostromedial tegmental nucleus (RMTg) arising from cortex, brainstem, and habenula that drive triply dissociable RMTg responses to aversive cues, outcomes, and prediction errors, respectively. These three pathways drive correspondingly dissociable aspects of punishment learning. The RMTg in turn drives negative, but not positive, valence encoding patterns in the ventral tegmental area (VTA). Hence, punishment learning involves pathways and functions that are highly distinct, yet tightly coordinated.

Keywords: RMTg; VTA; aversion; dopamine; habenula; learning; parabrachial; prefrontal; punishment; valence.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Learning / physiology*
  • Male
  • Neural Pathways / physiology*
  • Neurons, Afferent / physiology
  • Punishment*
  • Rats
  • Rats, Sprague-Dawley
  • Reward*
  • Tegmentum Mesencephali / physiology*
  • Ventral Tegmental Area / physiology