Neurogenetics and pharmacology of learning, motivation, and cognition.
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.
Frank
Michael J
MJ
Department of Cognitive, Linguistic and Psychological Sciences, Brown Institute for Brain Science, Brown University, Providence, RI 02912-1978, USA. michael_frank@brown.edu
Fossella
John A
JA
D000818:Animals; D003071:Cognition / Q000502:physiology; D003342:Corpus Striatum / Q000737:chemistry / Q000502:physiology*; D004298:Dopamine / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D007858:Learning / Q000502:physiology; D009042:Motivation / Q000235:genetics; D011110:Polymorphism, Genetic; D017397:Prefrontal Cortex / Q000737:chemistry / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000235:genetics; D050638:Receptors, Dopamine D4 / Q000235:genetics
C493599:DRD4 protein, human; D050483:Dopamine Plasma Membrane Transport Proteins; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; C497928:PPP1R1B protein, human; D017448:Receptors, Dopamine D2; C493214:SLC6A3 protein, human; D050638:Receptors, Dopamine D4; D004298:Dopamine