Brain stimulation reward is integrated by a network of electrically coupled GABA neurons

Brain Res. 2007 Jul 2:1156:46-58. doi: 10.1016/j.brainres.2007.04.053. Epub 2007 Apr 25.


The neural substrate of brain stimulation reward (BSR) has eluded identification since its discovery more than a half-century ago. Notwithstanding the difficulties in identifying the neuronal integrator of BSR, the mesocorticolimbic dopamine (DA) system originating in the ventral tegmental area (VTA) of the midbrain has been implicated. We have previously demonstrated that the firing rate of a subpopulation of gamma-aminobutyric acid (GABA) neurons in the VTA increases in anticipation of BSR. We show here that GABA neurons in the VTA, midbrain, hypothalamus, and thalamus of rats express connexin-36 (Cx36) gap junctions (GJs) and couple electrically upon DA application or by stimulation of the internal capsule (IC), which also supports self-stimulation. The threshold for responding for IC self-stimulation was the threshold for electrical coupling between GABA neurons, the degree of responding for IC self-stimulation was proportional to the magnitude of electrical coupling between GABA neurons, and GJ blockers increased the threshold for IC self-stimulation without affecting performance. Thus, a network of electrically coupled GABA neurons in the ventral brain may form the elusive neural integrator of BSR.

Publication types

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

MeSH terms

  • Animals
  • Brain / physiology*
  • Connexins / genetics
  • Electric Stimulation
  • Gene Expression Regulation
  • In Situ Hybridization, Fluorescence
  • Neurons / physiology*
  • Rats
  • Reward*
  • Self Stimulation
  • Ventral Tegmental Area / physiology
  • gamma-Aminobutyric Acid / physiology*


  • Connexins
  • connexin 36
  • gamma-Aminobutyric Acid