Molecular substrates of action control in cortico-striatal circuits

Prog Neurobiol. 2011 Sep 15;95(1):1-13. doi: 10.1016/j.pneurobio.2011.05.007. Epub 2011 Jun 17.


The purpose of this review is to describe the molecular mechanisms in the striatum that mediate reward-based learning and action control during instrumental conditioning. Experiments assessing the neural bases of instrumental conditioning have uncovered functional circuits in the striatum, including dorsal and ventral striatal sub-regions, involved in action-outcome learning, stimulus-response learning, and the motivational control of action by reward-associated cues. Integration of dopamine (DA) and glutamate neurotransmission within these striatal sub-regions is hypothesized to enable learning and action control through its role in shaping synaptic plasticity and cellular excitability. The extracellular signal regulated kinase (ERK) appears to be particularly important for reward-based learning and action control due to its sensitivity to combined DA and glutamate receptor activation and its involvement in a range of cellular functions. ERK activation in striatal neurons is proposed to have a dual role in both the learning and performance factors that contribute to instrumental conditioning through its regulation of plasticity-related transcription factors and its modulation of intrinsic cellular excitability. Furthermore, perturbation of ERK activation by drugs of abuse may give rise to behavioral disorders such as addiction.

Publication types

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

MeSH terms

  • Animals
  • Cerebral Cortex / anatomy & histology*
  • Cerebral Cortex / physiology*
  • Conditioning, Classical / physiology
  • Corpus Striatum / anatomy & histology*
  • Corpus Striatum / physiology*
  • Dopamine / metabolism
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Glutamic Acid / metabolism
  • Humans
  • Learning / physiology
  • Neural Pathways / anatomy & histology*
  • Neural Pathways / physiology*
  • Neuronal Plasticity / physiology
  • Reward


  • Glutamic Acid
  • Extracellular Signal-Regulated MAP Kinases
  • Dopamine