Basal forebrain parvalbumin neurons modulate vigilant attention and rescue deficits produced by sleep deprivation

Attention is impaired in many neuropsychiatric disorders, as well as by sleep disruption, leading to decreased workplace productivity and increased risk of accidents. Thus, understanding the neural substrates is important. Here we test the hypothesis that basal forebrain neurons that contain the calcium-binding protein parvalbumin modulate vigilant attention in mice. Furthermore, we test whether increasing the activity of basal forebrain parvalbumin neurons can rescue the deleterious effects of sleep deprivation on vigilance. A lever release version of the rodent psychomotor vigilance test was used to assess vigilant attention. Brief and continuous low-power optogenetic excitation (1 s, 473 nm @ 5 mW) or inhibition (1 s, 530 nm @ 10 mW) of basal forebrain parvalbumin neurons was used to test the effect on attention, as measured by reaction time, under control conditions and following 8 hr of sleep deprivation by gentle handling. Optogenetic excitation of basal forebrain parvalbumin neurons that preceded the cue light signal by 0.5 s improved vigilant attention as indicated by quicker reaction times. By contrast, both sleep deprivation and optogenetic inhibition slowed reaction times. Importantly, basal forebrain parvalbumin excitation rescued the reaction time deficits in sleep-deprived mice. Control experiments using a progressive ratio operant task confirmed that optogenetic manipulation of basal forebrain parvalbumin neurons did not alter motivation. These findings reveal for the first time a role for basal forebrain parvalbumin neurons in attention, and show that increasing their activity can compensate for disruptive effects of sleep deprivation.