BLR&D Research Career Scientist Award Application
BLR
基本信息
- 批准号:10454221
- 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:2018
- 资助国家:美国
- 起止时间:2018-04-01 至 2025-03-31
- 项目状态:未结题
- 来源:
- 关键词:3-DimensionalAgingAmericanAnxietyAreaArousalAtypical depressive disorderAutopsyAwardBehaviorBehavioral SymptomsBooksBrainBrain MappingBrain imagingComplexDataDefectDiseaseDrowsinessEmotionalEnvironmentFDA approvedFluorescenceFundingGene TransferGeneral PopulationGenerationsGenetic EngineeringGenetically Engineered MouseGoalsGrantGrant ReviewGrowth and Development functionHeartHypothalamic structureImageIndividualInjuryInternationalJet Lag SyndromeJournalsKidneyLaboratoriesLaboratory ResearchLifeLimbic SystemLinkLiverMagnetic Resonance ImagingMalignant NeoplasmsMammalsMapsMeasuresMemoryMental DepressionMentorsMethodologyMethodsMicroscopeMicrotomyModern MedicineMolecularMoodsMusNarcolepsyNerve DegenerationNeurobiologyNeurodegenerative DisordersNeuronsNeurosciencesObstructive Sleep ApneaPathologyPatientsPeer ReviewPharmacogeneticsPhenotypePhilosophyPost-Traumatic Stress DisordersProsthesisProteinsPublishingRattusResearchResearch PersonnelResolutionReview CommitteeRodent ModelScienceScientistSeriesServicesSignal TransductionSleepSleep DeprivationSleep DisordersSleep disturbancesSleeplessnessSliceSpinal CordStrokeStudentsSubstance abuse problemTestingTimeTissuesTrainingTraumaTraumatic Brain InjuryUnited States National Institutes of HealthVeteransVisualWakefulnessWorkawakebrain tissuecalcium indicatorcareercell typeconditioned fearemotional behaviorexperienceexperimental studyfallshypnotichypocretinimaging modalityinterestliver imagingmicroendoscopemild traumatic brain injurymouse modelneural circuitneuronal circuitrynon-alcoholic fatty liver diseaseoptogeneticspost-traumatic symptomsprogramsreconstructionskillstooltranslational potentialwound healing
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、情绪和记忆力下降
睡眠不足,持续睡眠不足会变得更糟。睡眠障碍是一种常见的
我们退伍军人中常见的抱怨。过度唤醒导致的睡眠不足是创伤后应激障碍的症状之一,但事实并非如此
不知道为什么患有创伤后应激障碍的退伍军人无法入睡。我的研究重点是识别和绘制
诱导睡眠的脑神经元。我的研究的总体影响是它将提供第一个直接的
将神经元的特定表型与其负责诱导睡眠的回路联系起来的证据。这将使
在唤醒动力非常强的情况下,例如在失眠的情况下,可以诱导睡眠
创伤后应激障碍,或在过度困倦时保持清醒,如阻塞性疾病患者
睡眠呼吸暂停或不典型抑郁症。
一系列实验使用光遗传学和药物遗传学来识别大脑中的功能回路
大脑。大脑包含许多不同类型的细胞,通过光遗传学和药物遗传学
现在有可能分解大脑以识别负责复杂行为的罪魁祸首神经元,如
作为睡眠。我的实验室是睡眠神经生物学领域第一个使用光遗传学诱导睡眠的实验室。
(Konadhode等人,2013年,所附)。我们激活了下丘脑中的一种特定表型的神经元
发现在一天中老鼠应该醒着的时候,它会诱导睡眠。我们现在有了
在老鼠身上也显示了同样的效果,这表明激活这些神经元会在哺乳动物中驱动睡眠。我们现在
想要测试在高唤醒状态下的睡眠诱导效果,例如恐惧条件反射(PTSD)或焦虑。
结合光遗传学和药物遗传学,我正在使用大脑深部成像方法来
想象一下大脑中特定表型神经元的活动。此方法测量
单个神经元中遗传编码的钙指示剂的荧光。荧光信号是
通过附在微型显微镜(2g)上的显微内窥镜拍摄。显微内窥镜可以放置在
在老鼠大脑中的任何地方提供了前所未有的神经元活动记录。我在用它来获取
睡眠和清醒时特定神经元回路活动的视觉证据。
另一系列研究使用Clarity方法来描绘由光遗传学激活的电路。
Clarity是一种新的神经解剖学方法,它使死后组织,如大脑,变得透明。
PI与RHJVAMC的研究人员合作,获得了蔡司光片显微镜,并将其用于
制作脑神经元电路的3D重建(见Shiroomi and Peever,2017年附件)。我的意图是
为了使用Clarity来可视化脑外伤啮齿动物模型的死后大脑,并成像一个透明的心脏,
肝和肾。其目标是提供病变组织中回路断裂的可视记录。
第四系列实验使用基因转移方法修复有缺陷的电路并恢复
行为。我已经成功地用它纠正了小鼠模型中的行为症状
神经退行性睡眠障碍,嗜睡症。我们现在正在使用基因转移的方法来阻止触发
异常行为,例如在恐惧条件反射中。总体而言,这些神经科学方法和工具有助于
RHJ VAMC的集体研究工作。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
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
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ 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:
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:
相似海外基金
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:
10910604 - 财政年份:2023
- 资助金额:
-- - 项目类别:
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:
10370185 - 财政年份:2022
- 资助金额:
-- - 项目类别:
50th Annual Meeting of the American Aging Association
美国老龄化协会第 50 届年会
- 批准号:
10468570 - 财政年份:2022
- 资助金额:
-- - 项目类别:
The Black American United Memory & Aging Project (BA-UMAP): An examination of cognitive decline in midlife and older Black adults using remote cognitive assessments, risk factors & biomarkers
美国黑人联合记忆
- 批准号:
10686987 - 财政年份:2022
- 资助金额:
-- - 项目类别:
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:
10565869 - 财政年份:2022
- 资助金额:
-- - 项目类别:
The Black American United Memory & Aging Project (BA-UMAP): An examination of cognitive decline in midlife and older Black adults using remote cognitive assessments, risk factors & biomarkers
美国黑人联合记忆
- 批准号:
10526152 - 财政年份:2022
- 资助金额:
-- - 项目类别:
51st Annual Meeting of the American Aging Association
美国老龄化协会第 51 届年会
- 批准号:
10602831 - 财政年份:2022
- 资助金额:
-- - 项目类别:
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)
- 批准号:
10460942 - 财政年份:2021
- 资助金额:
-- - 项目类别:
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)
- 批准号:
10172529 - 财政年份:2021
- 资助金额:
-- - 项目类别:
Diversity Supplement to Psychosocial Stress due to COVID-19 and Vascular Aging in African-American Women
对非裔美国女性因 COVID-19 和血管老化造成的心理社会压力进行多样性补充
- 批准号:
10709289 - 财政年份:2021
- 资助金额:
-- - 项目类别:














{{item.name}}会员




