GABA neurons of the VTA drive conditioned place aversion

Neuron. 2012 Mar 22;73(6):1173-83. doi: 10.1016/j.neuron.2012.02.015. Epub 2012 Mar 21.

Abstract

Salient but aversive stimuli inhibit the majority of dopamine (DA) neurons in the ventral tegmental area (VTA) and cause conditioned place aversion (CPA). The cellular mechanism underlying DA neuron inhibition has not been investigated and the causal link to behavior remains elusive. Here, we show that GABA neurons of the VTA inhibit DA neurons through neurotransmission at GABA(A) receptors. We also observe that GABA neurons increase their firing in response to a footshock and provide evidence that driving GABA neurons with optogenetic effectors is sufficient to affect behavior. Taken together, our data demonstrate that synaptic inhibition of DA neurons drives place aversion.

Publication types

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

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / genetics
  • Analgesics, Opioid / pharmacology
  • Analysis of Variance
  • Animals
  • Apomorphine / pharmacology
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Channelrhodopsins
  • Conditioning, Operant / drug effects
  • Conditioning, Operant / physiology*
  • Dopamine Agonists / pharmacology
  • Dopamine Antagonists / pharmacology
  • Dopaminergic Neurons / drug effects
  • Dopaminergic Neurons / physiology*
  • Electroshock / adverse effects
  • Escape Reaction / drug effects
  • Escape Reaction / physiology*
  • G Protein-Coupled Inwardly-Rectifying Potassium Channels / deficiency
  • G Protein-Coupled Inwardly-Rectifying Potassium Channels / genetics
  • GABAergic Neurons / drug effects
  • GABAergic Neurons / physiology*
  • Glutamate Decarboxylase / genetics
  • Haloperidol / pharmacology
  • In Vitro Techniques
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Morphine / pharmacology
  • Optics and Photonics
  • Time Factors
  • Tyrosine 3-Monooxygenase / genetics
  • Tyrosine 3-Monooxygenase / metabolism
  • Ventral Tegmental Area / cytology*
  • Ventral Tegmental Area / drug effects

Substances

  • Analgesics, Opioid
  • Bacterial Proteins
  • Channelrhodopsins
  • Dopamine Agonists
  • Dopamine Antagonists
  • G Protein-Coupled Inwardly-Rectifying Potassium Channels
  • Kcnj6 protein, mouse
  • Luminescent Proteins
  • yellow fluorescent protein, Bacteria
  • Morphine
  • Tyrosine 3-Monooxygenase
  • Glutamate Decarboxylase
  • glutamate decarboxylase 2
  • Haloperidol
  • Apomorphine