Synaptic and behavioral profile of multiple glutamatergic inputs to the nucleus accumbens

Neuron. 2012 Nov 21;76(4):790-803. doi: 10.1016/j.neuron.2012.09.040.


Excitatory afferents to the nucleus accumbens (NAc) are thought to facilitate reward seeking by encoding reward-associated cues. Selective activation of different glutamatergic inputs to the NAc can produce divergent physiological and behavioral responses, but mechanistic explanations for these pathway-specific effects are lacking. Here, we compared the innervation patterns and synaptic properties of ventral hippocampus, basolateral amygdala, and prefrontal cortex input to the NAc. Ventral hippocampal input was found to be uniquely localized to the medial NAc shell, where it was predominant and selectively potentiated after cocaine exposure. In vivo, bidirectional optogenetic manipulations of this pathway attenuated and enhanced cocaine-induced locomotion. Challenging the idea that any of these inputs encode motivationally neutral information, activation of each discrete pathway reinforced instrumental behaviors. Finally, direct optical activation of medium spiny neurons proved to be capable of supporting self-stimulation, demonstrating that behavioral reinforcement is an explicit consequence of strong excitatory drive to the NAc.

Publication types

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

MeSH terms

  • Analysis of Variance
  • Animals
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Biophysics
  • Cerebral Cortex / physiology
  • Channelrhodopsins
  • Cocaine / pharmacology
  • Dopamine Uptake Inhibitors / pharmacology
  • Electric Stimulation
  • Glutamic Acid / metabolism*
  • Hippocampus / physiology
  • Light
  • Locomotion / drug effects
  • Locomotion / physiology*
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Male
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Mice
  • Mice, Inbred C57BL
  • Microinjections
  • Neural Pathways / physiology
  • Neurons / physiology*
  • Nucleus Accumbens / cytology*
  • Nucleus Accumbens / metabolism*
  • Optogenetics
  • Patch-Clamp Techniques
  • Stilbamidines / metabolism
  • Synapses / drug effects
  • Synapses / physiology*
  • Transduction, Genetic


  • 2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt
  • Bacterial Proteins
  • Channelrhodopsins
  • Dopamine Uptake Inhibitors
  • Luminescent Proteins
  • Stilbamidines
  • yellow fluorescent protein, Bacteria
  • Glutamic Acid
  • Cocaine