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Annotation

Zhang Y, Bertolino A, Fazio L, Blasi G, Rampino A, Romano R, Lee ML, Xiao T, Papp A, Wang D, Sadée W. Polymorphisms in human dopamine D2 receptor gene affect gene expression, splicing, and neuronal activity during working memory. Proc Natl Acad Sci U S A . 2007 Dec 18 ; 104(51):20552-7. PubMed Abstract

Comments on Paper and Primary News
Primary News: Genetic Variation Linked to Dopamine D2 Receptor Levels and Working Memory

Comment by:  Michael J. Frank
Submitted 21 December 2007 Posted 21 December 2007

First, Zhang and colleagues examine multiple polymorphisms in the D2 receptor gene and find that none of the "standard" ones that have been linked to clinical characteristics actually affected D2 receptor density in prefrontal cortex or striatum. However, they find that two other, previously unstudied polymorphisms altered the relative expression of short versus long isoforms of the D2 receptor, likely reflecting presynaptic and postsynaptic D2 receptors, respectively. These findings could provide a basis for understanding several perplexing effects in the literature, such as opposing effects of D2 receptor drugs on cognition in individuals with low and high working memory ability, who are shown here to have differential pre- versus postsynaptic D2 receptor function.

Further, the presynaptic receptor is thought to regulate phasic dopamine signaling via its autoreceptor functions (in addition to controlling glutamate release in corticostriatal terminals via the heteroreceptors alluded to in the article). Thus, based on current evidence, it is expected that these...  Read more


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