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The inverted U- alterations in PFC function based on arousal state


Coordinating Arousal with Cognition

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Understanding how neuromodulators influence dlPFC circuits helps to explain how higher cognition is altered by our state of arousal. In deep sleep we may be unconscious due to the absence of acetylcholine stimulation of nic-α7R which is permissive for NMDA actions. When we are awake, cholinergic stimulation of nic-α7R allows networks to connect. Moderate levels of norepinephrine release in response to interesting events stimulates α2A-AR, which strengthens preferred connections and promotes PFC cognitive abilities. Dopamine is also released to salient events, which gates out nonpreferred network inputs through stimulation of D1R. Low levels of dopamine D1R sculpting may be optimal for creative thinking when a broad range of inputs are needed, while moderate levels of D1R stimulation may be optimal for tasks requiring precise focus. In contrast, high levels of norepinephrine and dopamine release during stress suppress neuronal firing and impair prefrontal function through a α1R and D1R, respectively.

If you are interested: Arnsten AFT, Wang MJ, Paspalas CD (2012) Neuromodulation of thought: Flexibilities and vulnerabilities in prefrontal cortical network synapses. Neuron 76: 223-239.