Strecker, R. E. | Search bioRxiv

bioRxiv2021

Basal forebrain parvalbumin neurons modulate vigilant attention.

Attention 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. HIGHLIGHTSO_LIOptogenetic methods tested the neural circuitry of vigilant attention in mice C_LIO_LIExcitation of basal forebrain parvalbumin neurons quickened reaction times C_LIO_LISleep deprivation or inhibition of parvalbumin neurons slowed reaction times C_LIO_LIExcitation of parvalbumin neurons rescued deficits produced by sleep deprivation C_LI

neuroscience↗

bioRxiv2019

Basal forebrain parvalbumin neurons mediate arousals from sleep induced by hypercarbia or auditory stimuli

Brief arousals from sleep in patients with sleep apnea and other disorders prevent restful sleep, and contribute to cognitive, metabolic and physiologic dysfunction. Little is currently known about which neural systems mediate these brief arousals, hindering the development of treatments. The basal forebrain (BF) receives inputs from many nuclei of the ascending arousal system. These inputs include the brainstem parabrachial neurons which promote arousal in response to elevated blood carbon dioxide levels, as seen in sleep apnea. Optical inhibition of the terminals of parabrachial neurons in the BF impairs cortical arousals to hypercarbia, but which cell types within the BF mediate cortical arousals in response to hypercarbia or other sensory stimuli is unknown. Here using optogenetic techniques in mice, we show that BF parvalbumin (PV) neurons fulfill several criteria for a system mediating brief arousals from sleep. Optical stimulation of BF PV neurons during the light period, when mice normally sleep, caused rapid transitions to wakefulness and increased wake bout durations. Unlike many other ascending arousal systems, arousals induced by stimulation of BF PV neurons were brief, resulting in only a small (13.6%) increase in the total amount of wakefulness. Bilateral optical inhibition of BF PV neurons increased the latency to arousal produced by hypercarbia or auditory stimuli. Thus, BF PV neurons are an important component of the brain circuitry which generates brief arousals from sleep in response to internal and external sensory stimuli.

neuroscience↗