Loss of UBE3A from TH-expressing neurons suppresses GABA co-release and enhances VTA-NAc optical self-stimulation

Nat Commun. 2016 Feb 12;7:10702. doi: 10.1038/ncomms10702.

Abstract

Motivated reward-seeking behaviours are governed by dopaminergic ventral tegmental area projections to the nucleus accumbens. In addition to dopamine, these mesoaccumbal terminals co-release other neurotransmitters including glutamate and GABA, whose roles in regulating motivated behaviours are currently being investigated. Here we demonstrate that loss of the E3-ubiquitin ligase, UBE3A, from tyrosine hydroxylase-expressing neurons impairs mesoaccumbal, non-canonical GABA co-release and enhances reward-seeking behaviour measured by optical self-stimulation.

Publication types

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

MeSH terms

  • Animals
  • Behavior, Animal*
  • Dopamine / metabolism*
  • Dopaminergic Neurons / metabolism*
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Motivation / genetics*
  • Neural Pathways
  • Neurons / metabolism
  • Nucleus Accumbens / metabolism*
  • Optogenetics
  • Patch-Clamp Techniques
  • Reinforcement, Psychology
  • Reward
  • Self Stimulation*
  • Stereotaxic Techniques
  • Synaptic Transmission / genetics
  • Tyrosine 3-Monooxygenase / metabolism*
  • Ubiquitin-Protein Ligases / genetics*
  • Ventral Tegmental Area / cytology
  • Ventral Tegmental Area / metabolism*
  • gamma-Aminobutyric Acid / metabolism*

Substances

  • gamma-Aminobutyric Acid
  • Tyrosine 3-Monooxygenase
  • Ube3a protein, mouse
  • Ubiquitin-Protein Ligases
  • Dopamine