Neurogenetics and pharmacology of learning, motivation, and cognition

Neuropsychopharmacology. 2011 Jan;36(1):133-52. doi: 10.1038/npp.2010.96. Epub 2010 Jul 14.


Many of the individual differences in cognition, motivation, and learning-and the disruption of these processes in neurological conditions-are influenced by genetic factors. We provide an integrative synthesis across human and animal studies, focusing on a recent spate of evidence implicating a role for genes controlling dopaminergic function in frontostriatal circuitry, including COMT, DARPP-32, DAT1, DRD2, and DRD4. These genetic effects are interpreted within theoretical frameworks developed in the context of the broader cognitive and computational neuroscience literature, constrained by data from pharmacological, neuroimaging, electrophysiological, and patient studies. In this framework, genes modulate the efficacy of particular neural computations, and effects of genetic variation are revealed by assays designed to be maximally sensitive to these computations. We discuss the merits and caveats of this approach and outline a number of novel candidate genes of interest for future study.

Publication types

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

MeSH terms

  • Animals
  • Cognition / physiology
  • Corpus Striatum / chemistry
  • Corpus Striatum / physiology*
  • Dopamine / deficiency
  • Dopamine / genetics
  • Dopamine / metabolism*
  • Dopamine Plasma Membrane Transport Proteins / genetics
  • Dopamine and cAMP-Regulated Phosphoprotein 32 / genetics
  • Genetic Variation / genetics
  • Humans
  • Learning / physiology
  • Motivation / genetics
  • Polymorphism, Genetic
  • Prefrontal Cortex / chemistry
  • Prefrontal Cortex / physiology*
  • Receptors, Dopamine D2 / genetics
  • Receptors, Dopamine D4 / genetics


  • DRD4 protein, human
  • Dopamine Plasma Membrane Transport Proteins
  • Dopamine and cAMP-Regulated Phosphoprotein 32
  • PPP1R1B protein, human
  • Receptors, Dopamine D2
  • SLC6A3 protein, human
  • Receptors, Dopamine D4
  • Dopamine