Enhanced Control of Attention by Stimulating Mesolimbic-Corticopetal Cholinergic Circuitry

Sustaining and recovering attentional performance requires interactions between the brain's motivation and attention systems. The first experiment demonstrated that in rats performing a sustained attention task ( SAT), presentation of a distractor (dSAT) augmented performance-associated increases in cholinergic neurotransmission in prefrontal cortex. Because stimulation of NMDA receptors in the shell of the nucleus accumbens activates PFC cholinergic neurotransmission, a second experiment demonstrated that bilateral infusions of NMDA into the NAc shell, but not core, improved dSAT performance to levels observed in the absence of a distractor. A third experiment demonstrated that removal of prefrontal or posterior parietal cholinergic inputs, by intracortical infusions of the cholinotoxin 192 IgG-saporin, attenuated the beneficial effects of NMDA on dSAT performance. Mesolimbic activation of cholinergic projections to the cortex benefits the cognitive control of attentional performance by enhancing the detection of cues and the filtering of distractors.