BLR&D Research Career Scientist Award Application

BLR

基本信息

项目摘要

70 million Americans suffer from some sort of sleep disorder. Behavior, mood and memory deteriorate with sleep loss and it gets worse with continuing sleep deprivation. Sleep disturbance is a frequent and common complaint among our Veterans. Lack of sleep due to hyperarousal is one symptom of PTSD, but it is not known why Veterans with PTSD cannot fall asleep. My research focuses on identifying and mapping the brain neurons that induce sleep. The overall impact of my research is that it will provide the first direct evidence linking specific phenotypes of neurons and their circuits responsible for inducing sleep. This will make it possible to induce sleep in conditions where the arousal drive is very strong, such as in the insomnia of PTSD, or to maintain wakefulness when there is excessive sleepiness, such as in patients with obstructive sleep apnea or atypical depression. One series of experiments uses optogenetics and pharmacogenetics to identify functional circuits in the brain. The brain contains many different types of cells and through optogenetics and pharmacogenetics it is now possible to disassemble the brain to identify the culprit neurons responsible for complex behaviors, such as sleep. My lab was the first in the area of sleep neurobiology to use optogenetics to induce sleep (Konadhode et al., 2013, attached). We activated a specific phenotype of neurons in the hypothalamus and discovered that it induced sleep at a time of day when the mouse should have been awake. We have now shown the same effect in rats, indicating that activating these neurons drives sleep across mammals. We now want to test the sleep-inducing effect in conditions of high arousal, such as fear-conditioning (PTSD) or anxiety. In conjunction with optogenetics and pharmacogenetics, I am using the deep-brain imaging method to image the activity of phenotype-specific neurons in the brains. This method measures changes in fluorescence of a genetically encoded calcium indicator in individual neurons. The fluorescence signal is captured via a microendoscope attached to a miniature microscope (2g). The microendoscope can be placed anywhere in the brains of mice providing unprecedented record of neuronal activity. I am using it to obtain visual evidence of the activity of specific neuronal circuits during sleep and waking. Another series of studies uses the CLARITY method to map the circuit activated by optogenetics. CLARITY is a new neuroanatomical method that makes postmortem tissue, such as the brain, transparent. The PI collaborated with RHJVAMC researchers to acquire a Zeiss Lightsheet microscope and used it to produce a 3D reconstruction of brain neuronal circuits (see Shiromani and Peever, 2017 attached). My intent is to use CLARITY to visualize postmortem brains in rodent models of TBI, and also image a transparent heart, liver and kidney. The goal is to provide a visual record of the break in a circuit in diseased tissue. The fourth series of experiments use the gene transfer approach to fix defective circuits and restore behavior. I have used it to successfully to correct behavioral symptoms in a mouse model of the neurodegenerative sleep disorder, narcolepsy. We are now using the gene transfer method to block triggering of abnormal behavior, for example in fear-conditioning. Overall, these neuroscience methods and tools aid the collective research effort at RHJ VAMC.
7000万美国人患有某种睡眠障碍。行为、情绪和记忆都会恶化

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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Priyattam J. Shiromani其他文献

Usando neurotoxinas para entender el circuito cerebral que regula el ciclo vigilia-sueño
神经毒素对大脑回路的调节作用
  • DOI:
  • 发表时间:
    2008
  • 期刊:
  • 影响因子:
    0
  • 作者:
    C. B. Centurión;Priyattam J. Shiromani
  • 通讯作者:
    Priyattam J. Shiromani
Different neuronal phenotypes in the lateral hypothalamus and their role in sleep and wakefulness
  • DOI:
    10.1385/mn:29:1:41
  • 发表时间:
    2004-01-01
  • 期刊:
  • 影响因子:
    4.300
  • 作者:
    Dmitry Gerashchenko;Priyattam J. Shiromani
  • 通讯作者:
    Priyattam J. Shiromani
The relative effects of selective M<sub>1</sub> muscarinic antagonists on rapid eye movement sleep
  • DOI:
    10.1016/0006-8993(93)91457-4
  • 发表时间:
    1993-04-16
  • 期刊:
  • 影响因子:
  • 作者:
    Rebecca K. Zoltoski;Javier Velazquez-Moctezuma;Priyattam J. Shiromani;J. Christian Gillin
  • 通讯作者:
    J. Christian Gillin

Priyattam J. Shiromani的其他文献

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{{ truncateString('Priyattam J. Shiromani', 18)}}的其他基金

Neuronal Activity in Sleep & Wake in Alzheimer's Disease Mice
睡眠中的神经元活动
  • 批准号:
    10723302
  • 财政年份:
    2023
  • 资助金额:
    --
  • 项目类别:
ShEEP Request for iNSCOPIX nVue System
SheEEP 对 iNSCOPIX nVue 系统的请求
  • 批准号:
    10534510
  • 财政年份:
    2022
  • 资助金额:
    --
  • 项目类别:
BLR&D Research Career Scientist Award Application
BLR
  • 批准号:
    10618287
  • 财政年份:
    2018
  • 资助金额:
    --
  • 项目类别:
BLR&D Research Career Scientist Award Application
BLR
  • 批准号:
    10265393
  • 财政年份:
    2018
  • 资助金额:
    --
  • 项目类别:
BLR&D Research Career Scientist Award Application
BLR
  • 批准号:
    9899097
  • 财政年份:
    2018
  • 资助金额:
    --
  • 项目类别:
Astroglia-Neuron Regulation of Sleep
星形胶质细胞神经元对睡眠的调节
  • 批准号:
    9189564
  • 财政年份:
    2016
  • 资助金额:
    --
  • 项目类别:
Astroglial Orexin in Sleep Disorders
睡眠障碍中的星形胶质细胞食欲素
  • 批准号:
    8585663
  • 财政年份:
    2013
  • 资助金额:
    --
  • 项目类别:
Astroglial Orexin in Sleep Disorders
睡眠障碍中的星形胶质细胞食欲素
  • 批准号:
    8706253
  • 财政年份:
    2013
  • 资助金额:
    --
  • 项目类别:
Selective Activation of Neurons to Control Narcolepsy
选择性激活神经元来控制发作性睡病
  • 批准号:
    8488510
  • 财政年份:
    2012
  • 资助金额:
    --
  • 项目类别:
Selective Activation of Neurons to Control Narcolepsy
选择性激活神经元来控制发作性睡病
  • 批准号:
    8358785
  • 财政年份:
    2012
  • 资助金额:
    --
  • 项目类别:

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Indicators of Accelerated Aging in Asian American Childhood Survivors
亚裔美国童年幸存者加速衰老的指标
  • 批准号:
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  • 财政年份:
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    --
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50th Annual Meeting of the American Aging Association
美国老龄化协会第 50 届年会
  • 批准号:
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  • 财政年份:
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  • 资助金额:
    --
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Longitudinal Examination of Neighborhood Disadvantage, Cognitive Aging, and Alzheimer's Disease Risk in Disinvested, African American Neighborhoods
对投资撤资的非裔美国人社区的社区劣势、认知老化和阿尔茨海默病风险进行纵向调查
  • 批准号:
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    2022
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    --
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51st Annual Meeting of the American Aging Association
美国老龄化协会第 51 届年会
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Advancing Native American Diversity in Aging Research through Undergraduate Education (Native American ADAR)
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    --
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Advancing Native American Diversity in Aging Research through Undergraduate Education (Native American ADAR)
通过本科教育促进美国原住民老龄化研究的多样性(美国原住民 ADAR)
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