Basal forebrain parvalbumin neurons modulate vigilant attention

Abstract

SummaryAttention is impaired in many neuropsychiatric disorders1 and by sleep disruption, leading to decreased workplace productivity and increased risk of accidents2–4. Thus, understanding the underlying neural substrates is important for developing treatments. The basal forebrain (BF) is a brain region which degenerates in dementia5–7 and is implicated in the negative effects of sleep disruption on vigilance and cognition8,9. Previous studies demonstrated that the BF controls cortical fast oscillations that underlie attention10–12 and revealed the important role of cholinergic neurons13–15. However, the role of other neurochemically defined BF subtypes is unknown. Recent work has shown that one population of BF GABAergic neurons containing the calcium-binding protein parvalbumin (PV) control cortical fast oscillations and arousals from sleep16–19 but their role in awake behavior is unclear. Thus, here we test the hypothesis that BF-PV neurons modulate vigilant attention in mice. A lever release version of the rodent psychomotor vigilance test (rPVT) was used to assess vigilant attention as measured by reaction time. Brief and continuous low power optogenetic excitation of BF-PV neurons (1s,473nm@5mW) that preceded the cue light signal by 0.5s improved vigilant attention as indicated by quicker reaction times. In contrast, both sleep deprivation (8h) and optogenetic inhibition of BF-PV neurons (1s,530nm@10mW) slowed reaction times. Importantly, BF-PV excitation rescued the reaction time deficits in sleep deprived mice. These findings reveal for the first time a role for BF-PV neurons in attention.HIGHLIGHTSOptogenetic methods tested the neural circuitry of vigilant attention in miceExcitation of basal forebrain parvalbumin neurons quickened reaction timesSleep deprivation or inhibition of parvalbumin neurons slowed reaction timesExcitation of parvalbumin neurons rescued deficits produced by sleep deprivation