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Published online August 9, 2007, 10.1101/lm.558707
 LEARNING & MEMORY 14:554-563
©2007 by Cold Spring Harbor Laboratory Press; ISSN 1072-0502/07 $5.00
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Review
Molecular activity underlying working memory

Pramod K. Dash1, Anthony N. Moore, Nobuhide Kobori, and Jason D. Runyan

The Vivian L. Smith Center for Neurologic Research, and Department of Neurobiology and Anatomy, The University of Texas Medical School, Houston, Texas 77225, USA

The prefrontal cortex is necessary for directing thought and planning action. Working memory, the active, transient maintenance of information in mind for subsequent monitoring and manipulation, lies at the core of many simple, as well as high-level, cognitive functions. Working memory has been shown to be compromised in a number of neurological and psychiatric conditions and may contribute to the behavioral and cognitive deficits associated with these disorders. It has been theorized that working memory depends upon reverberating circuits within the prefrontal cortex and other cortical areas. However, recent work indicates that intracellular signals and protein dephosphorylation are critical for working memory. The present article will review recent research into the involvement of the modulatory neurotransmitters and their receptors in working memory. The intracellular signaling pathways activated by these receptors and evidence that indicates a role for Gq-initiated PI-PLC and calcium-dependent protein phosphatase calcineurin activity in working memory will be discussed. Additionally, the negative influence of calcium- and cAMP-dependent protein kinase (i.e., calcium/calmodulin-dependent protein kinase II (CaMKII), calcium/diacylglycerol-activated protein kinase C (PKC), and cAMP-dependent protein kinase A (PKA)) activities on working memory will be reviewed. The implications of these experimental findings on the observed inverted-U relationship between D1 receptor stimulation and working memory, as well as age-associated working memory dysfunction, will be presented. Finally, we will discuss considerations for the development of clinical treatments for working memory disorders.

Received February 16, 2007; accepted in revised form June 7, 2007.

1 Corresponding author.

E-mail p.dash{at}uth.tmc.edu; fax (713) 500-0621.

Article is online at http://www.learnmem.org/cgi/doi/10.1101/lm.558707


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