Health & Environmental Research Online (HERO)


Print Feedback Export to File
6727160 
Journal Article 
Review 
Neuromodulation of thought: flexibilities and vulnerabilities in prefrontal cortical network synapses 
Arnsten, AF; Wang, MJ; Paspalas, CD 
2012 
1 
Neuron
ISSN: 0896-6273
EISSN: 1097-4199 
76 
1 
223-239 
English 
23040817 
WOS:000309799000016 
This review describes unique neuromodulatory influences on working memory prefrontal cortical (PFC) circuits that coordinate cognitive strength with arousal state. Working memory arises from recurrent excitation within layer III PFC pyramidal cell NMDA circuits, which are afflicted in aging and schizophrenia. Neuromodulators rapidly and flexibly alter the efficacy of these synaptic connections, while leaving the synaptic architecture unchanged, a process called dynamic network connectivity (DNC). Increases in calcium-cAMP signaling open ion channels in long, thin spines, gating network connections. Inhibition of calcium-cAMP signaling by stimulating α2A-adrenoceptors on spines strengthens synaptic efficacy and increases network firing, whereas optimal stimulation of dopamine D1 receptors sculpts network inputs to refine mental representation. Generalized increases in calcium-cAMP signaling during fatigue or stress disengage dlPFC recurrent circuits, reduce firing and impair top-down cognition. Impaired DNC regulation contributes to age-related cognitive decline, while genetic insults to DNC proteins are commonly linked to schizophrenia.