Basal forebrain parvalbumin neurons modulate vigilant attention

Abstract

Attention is impaired in many neuropsychiatric disorders and by sleep disruption, leading to decreased workplace productivity and increased risk of accidents. Thus, understanding the underlying neural substrates is important for developing treatments. The basal forebrain (BF) is a brain region which degenerates in dementia and is implicated in the negative effects of sleep disruption on vigilance and cognition. Previous studies demonstrated that the BF controls cortical fast oscillations that underlie attention and revealed the important role of cholinergic neurons. 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 sleep 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.

Dual orexin/hypocretin receptor antagonism attenuates attentional impairments in an NMDA receptor hypofunction model of schizophrenia

“…In addition to putatively anticholinergic effects in the BF, dual orexin receptor antagonism may have indirectly addressed dizocilpine-induced dysfunctions of signal-driven input selection and cortical vigilance networks stemming via various non-cholinergic loci in the mesocorticolimbic system, including PV+ GABAergic neurons of the BF. These fast-spiking neurons - which have recently been shown to quicken reaction times in a rodent psychomotor vigilance task when optogenetically stimulated [75, 76] - are depolarized by orexins and are themselves sufficient to stimulate cortical arousal when exposed to OxA in animals with lesions to corticopetal cholinergic projections [43, 77]. Thus, frontocortical activation may be suppressed when blocking orexin receptors expressed on these neurons as well as orexin receptors located on cortical glutamatergic outputs to the BF, which synapse exclusively with these PV+ GABAergic neurons [78, 79].…”