期刊
NEURON
卷 76, 期 1, 页码 223-239出版社
CELL PRESS
DOI: 10.1016/j.neuron.2012.08.038
关键词
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资金
- National Institutes of Health (NIH) [PO1 AG030004, RL1AA017536, MH 09335401]
- NARSAD
- Alzheimer's Association
- Shire Pharmaceuticals
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 alpha 2A-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 dIPFC 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.
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