Role of the basal forebrain in sleep loss induced attention impairments

基底前脑在睡眠不足引起的注意力障碍中的作用

基本信息

  • 批准号:
    10359072
  • 负责人:
  • 金额:
    --
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2015
  • 资助国家:
    美国
  • 起止时间:
    2015-10-01 至 2025-03-31
  • 项目状态:
    未结题

项目摘要

Sleep loss and sleep disorders (e.g., sleep apnea) lead to excessive daytime sleepiness and impaired attention & cognition. The symptoms of sleep disturbance are now recognized as major contributors to accident rates and decreased workplace productivity. Attention, concentration, and cognitive problems are also a major feature of other disorders that are prevalent in US veterans – e.g., TBI, PTSD, Alzheimer's disease, depression, substance use disorder, and schizophrenia. Understanding the brain circuitry controlling attention will guide the development of treatments to ameliorate the attention and cognitive impairments of these conditions. Abundant evidence indicates that the basal forebrain (BF) region contains cortically projecting & wakefulness promoting neurons that are important for cortical activation, behavioral arousal/alertness, and attention. Although previous work has focused on the role of BF cholinergic neurons in attention, advances in optogenetic methods allow the investigation of BF parvalbumin (PV) containing GABAergic neurons. Work on our current Merit grant indicates that selective excitation of BF PV neurons in mice produces cortical activation, wakefulness, and behavioral arousal. Our new preliminary data suggest that excitation of BF PV neurons can enhance attention, cognition, and rescue reaction time performance impairments produced by sleep loss. The findings described led us to two testable hypotheses: 1) BF PV neurons mediate rapid changes in alertness/attention by quickly activating the cortex in response to meaningful or surprising sensory stimuli. 2) Excitation of BF PV neurons does not alter motivation (e.g., hunger) and is not rewarding indicating these neurons can enhance attention and cognition with limited side effects and low addictive potential. Our model prediction: In response to meaningful or surprising sensory stimuli, BF PV neurons briefly activate the cortex, enhancing cortical processing and alertness which facilitates attention-dependent reaction time performance and associative learning. The work will address a gap in our knowledge by demonstrating that regulation of cortical activation by BF PV neurons is important for the control of attention. Methods used include fiber photometry to measure the activity of BF PV neurons and optogenetics to excite and inhibit these neurons in mice; both will be combined with behavioral tests and measures of cortical electrical activity. The 3 aims are: Aim 1 will demonstrate that increasing and decreasing the activity of BF PV neurons can modulate cortical responses to repetitive presentations of sensory stimuli. This finding will provide a plausible mechanism for how these neurons enhance the attention dependent behavioral performance studied in Aims 2 & 3. Aim 2 will demonstrate that BF PV excitation enhances sustained attention and performance in a mouse reaction time test like the test used in humans to detect sleepiness and sustained attention deficits. Experiments will demonstrate that sleep deprivation (SD) and BF PV inhibition slows reaction times, whereas BF PV excitation will quicken reaction times and will rescue deficits produced by SD. Aim 3. Attention is also important for learning and here BF PV manipulations are used to alter the attention needed for associative learning. Our predictions, supported by preliminary data, are that BF PV excitation enhances associative learning by broadcasting `surprise' signals to the cortex that are encoded in high frequency cortical gamma oscillations, and that BF PV excitation does not affect reward pathways. We also predict that BF PV inhibition and SD will impair attention-dependent associative learning. If successful, this project will show that the BF PV neuron excitation model enhances attention and cognition with limited side effects and low addictive potential. This model can be readily applied to mouse models of other conditions that are prevalent in the US Veteran population. Future work could also identify novel therapeutics to pharmacologically target receptors on BF PV neurons in order to activate them.
睡眠不足和睡眠障碍(如睡眠呼吸暂停)导致白天过度嗜睡和受损

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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ROBERT E STRECKER其他文献

ROBERT E STRECKER的其他文献

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{{ truncateString('ROBERT E STRECKER', 18)}}的其他基金

BLRD Research Career Scientist Award Application
BLRD 研究职业科学家奖申请
  • 批准号:
    10373036
  • 财政年份:
    2021
  • 资助金额:
    --
  • 项目类别:
BLRD Research Career Scientist Award Application
BLRD 研究职业科学家奖申请
  • 批准号:
    10618193
  • 财政年份:
    2021
  • 资助金额:
    --
  • 项目类别:
Role of the basal forebrain in sleep loss induced attention impairments
基底前脑在睡眠不足引起的注意力障碍中的作用
  • 批准号:
    10620170
  • 财政年份:
    2015
  • 资助金额:
    --
  • 项目类别:
Sleep loss impairment of arousal and cognition: role of the basal forebrain
睡眠不足对觉醒和认知的损害:基底前脑的作用
  • 批准号:
    8921583
  • 财政年份:
    2015
  • 资助金额:
    --
  • 项目类别:
Sleep loss impairment of arousal and cognition: role of the basal forebrain
睡眠不足对觉醒和认知的损害:基底前脑的作用
  • 批准号:
    9206087
  • 财政年份:
    2015
  • 资助金额:
    --
  • 项目类别:
Adenosine and the Basal Forebrain in the Control of Behavioral State
腺苷和基底前脑控制行为状态
  • 批准号:
    7786264
  • 财政年份:
    2009
  • 资助金额:
    --
  • 项目类别:
Adenosine and the Basal Forebrain in the Control of Behavioral State
腺苷和基底前脑控制行为状态
  • 批准号:
    7687191
  • 财政年份:
    2009
  • 资助金额:
    --
  • 项目类别:
Adenosine and the Basal Forebrain in the Control of Behavioral State
腺苷和基底前脑控制行为状态
  • 批准号:
    8195550
  • 财政年份:
    2009
  • 资助金额:
    --
  • 项目类别:
Adenosine and the Basal Forebrain in the Control of Behavioral State
腺苷和基底前脑控制行为状态
  • 批准号:
    8258633
  • 财政年份:
    2009
  • 资助金额:
    --
  • 项目类别:
DOPAMINE RELEASE INDUCED BY 4-METHYLAMINOREX
4-METHYLAMINOREX 诱导的多巴胺释放
  • 批准号:
    2119972
  • 财政年份:
    1991
  • 资助金额:
    --
  • 项目类别:

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