A role for prefrontal calcium-sensitive protein phosphatase and kinase activities in working memory.
The prefrontal cortex is involved in the integration and interpretation of information for directing thoughts and planning action. Working memory is defined as the active maintenance of information in mind and is thought to lie at the core of many prefrontal functions. Although dopamine and other neurotransmitters have been implicated, the intracellular events activated by their receptors that influence working memory are poorly understood. We demonstrate that working memory involves transient changes in prefrontal G(q/11)-signaling and in calcium-dependent intracellular protein phosphatase and kinase activity. Interestingly, inhibition of the calcium activated phosphatase calcineurin impaired, while calcium/calmodulin dependent kinase II (CaMKII) and calcium-dependent protein kinase C (PKC) enhanced, working memory. Our findings suggest that the active maintenance of information required for working memory involves transient changes in the balance of these enzymes' activities.
Runyan
Jason D
JD
The Vivian L. Smith Center for Neurological Research, Department of Neurobiology and Anatomy, The University of Texas Medical School, Houston, Texas 77225, USA.
Moore
Anthony N
AN
Dash
Pramod K
PK
D000818:Animals; D020013:Calcium Signaling / Q000502:physiology*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D004193:Discrimination Learning / Q000502:physiology; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000378:metabolism; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000201:enzymology*; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013998:Time Perception / Q000502:physiology
D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D010749:Phosphoprotein Phosphatases; D011494:Protein Kinases; D017447:Receptors, Dopamine D1