VA Boston Healthcare System and Department of Psychiatry, Harvard Medical School, Boston, Massachusetts, USA.
Genetics and Aging Research Unit, McCance Center for Brain Health, Mass General Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
J Sleep Res. 2024 May;33(3):e13919. doi: 10.1111/jsr.13919. Epub 2023 May 21.
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.
注意力在许多神经精神疾病以及睡眠障碍中受到损害，导致工作场所生产力下降和事故风险增加。因此，了解神经基础很重要。在这里，我们测试了这样一个假设，即含有钙结合蛋白 parvalbumin 的基底前脑神经元调节小鼠的警觉性注意力。此外，我们还测试了增加基底前脑 parvalbumin 神经元的活性是否可以挽救睡眠剥夺对警觉性的有害影响。使用啮齿动物精神运动性警觉测试的杠杆释放版本来评估警觉性注意力。短暂且连续的低功率光遗传学刺激（1s，473nm@5mW）或抑制（1s，530nm@10mW）基底前脑 parvalbumin 神经元，用于测试在对照条件下以及在经过 8 小时的轻柔处理睡眠剥夺后，注意力的影响，通过反应时间来衡量。在提示光信号之前 0.5s 刺激基底前脑 parvalbumin 神经元可改善警觉性注意力，表现为反应时间更快。相比之下，睡眠剥夺和光遗传学抑制都会使反应时间变慢。重要的是，基底前脑 parvalbumin 兴奋挽救了睡眠剥夺小鼠的反应时间缺陷。使用渐进比率操作任务的对照实验证实，基底前脑 parvalbumin 神经元的光遗传学操作不会改变动机。这些发现首次揭示了基底前脑 parvalbumin 神经元在注意力中的作用，并表明增加其活性可以补偿睡眠剥夺的破坏作用。
