A Central Amygdala-Substantia Innominata Neural Circuitry Encodes Aversive Reinforcement Signals

Cell Rep. 2017 Nov 14;21(7):1770-1782. doi: 10.1016/j.celrep.2017.10.062.


Aversive stimuli can impact motivation and support associative learning as reinforcers. However, the neural circuitry underlying the processing of aversive reinforcers has not been elucidated. Here, we report that a subpopulation of central amygdala (CeA) GABAergic neurons expressing protein kinase C-delta (PKC-δ+) displays robust responses to aversive stimuli during negative reinforcement learning. Importantly, projections from PKC-δ+ neurons of the CeA to the substantia innominata (SI) could bi-directionally modulate negative reinforcement learning. Moreover, consistent with the idea that SI-projecting PKC-δ+ neurons of the CeA encode aversive information, optogenetic activation of this pathway produces conditioned place aversion, a behavior prevented by simultaneous ablating of SI glutamatergic neurons. Taken together, our data define a cell-type-specific neural circuitry modulating associative learning by encoding aversive reinforcement signals.

Keywords: aversive signals; central amygdala; negative reinforcement learning; substantia innominate.

MeSH terms

  • Amygdala / cytology
  • Amygdala / metabolism
  • Amygdala / physiology*
  • Animals
  • Female
  • GABAergic Neurons / metabolism
  • GABAergic Neurons / physiology*
  • Glutamic Acid / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Protein Kinase C-delta / metabolism
  • Reward*
  • Substantia Innominata / cytology
  • Substantia Innominata / metabolism
  • Substantia Innominata / physiology*


  • Glutamic Acid
  • Protein Kinase C-delta