Role of thalamic modulation in motor learning
丘脑调节在运动学习中的作用
基本信息
- 批准号:10740323
- 负责人:
- 金额:$ 12.29万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-08-20 至 2025-07-31
- 项目状态:未结题
- 来源:
- 关键词:AcuteAdrenergic AgentsAnatomyAwardBasal GangliaBehaviorBrainBrain imagingBrain regionCerebellumCharacteristicsDevelopmentElectrophysiology (science)GoalsHeadImageIndividualInstitutionLearningLifeLocationMeasuresMentorsMolecularMonitorMotorMotor ActivityMotor CortexMotor SkillsMovementMovement DisordersMusNeuronsOutcomeParkinson DiseasePatternPhasePlayPositioning AttributePropertyResearchResearch PersonnelRoleSignal PathwaySignal TransductionSliceStructureTask PerformancesTestingThalamic structureTrainingViralcareercareer developmentexperienceexperimental studyin vivoin vivo two-photon imaginginsightlocus ceruleus structuremotor behaviormotor controlmotor disordermotor learningneuroregulationnovelnovel therapeutic interventionoptogeneticspharmacologicpreventsensorskillsspatiotemporaltwo-photon
项目摘要
PROJECT SUMMARY
Learning and executing motor skills are crucial functions of the brain and involve the coordinated activity of
multiple brain regions. Traditionally, the motor cortex (MCtx), the basal ganglia (BG), and the cerebellum (CB)
have been considered key motor control regions of the brain, and plasticity within these regions are known to
support motor learning. In addition, neuromodulation, such as from adrenergic neurons in the locus coeruleus
(LC), is critical for proper behavior and learning. Despite the key role these regions play in controlling
movements and their implication in movement disorders, we are only beginning to understand how motor
signals from these regions interact with each other. Anatomically, the thalamus serves as a common target
structure for MCtx, BG, and CB, yet conventionally, the thalamus has been viewed as a passive relay station.
However, there is emerging evidence that the thalamus can functionally integrate and modulate these diverse
motor signals. How thalamic neurons respond to motor inputs, the role of motor thalamus in motor learning,
and how adrenergic signaling modulates thalamic activity are largely undefined. My central hypothesis is that
the motor thalamus serves as a point of convergence for motor signals from MCtx, BG, and CB, as well as
neuromodulatory input from LC, allowing it to functionally integrate these inputs to control movements and
promote motor learning. I propose to use a combination of in vivo deep-brain imaging and novel fluorescent
sensors for intracellular signaling in mice performing motor tasks, as well as slice electrophysiology, to
measure the activity of motor thalamus during movement and determine how such activity is modulated by
adrenergic input from LC. These approaches will allow me to define the inputs to motor thalamus and measure
thalamic activity during movement and motor learning (Aim 1), determine the functional role of motor thalamus
and its inputs in motor control (Aim 2), and determine how adrenergic signaling modulates thalamic activity
during motor learning (Aim 3). Results from this study will not only clarify the role of the motor thalamus in
motor control and motor learning but also provide an understanding of how adrenergic neuromodulation
influences thalamic activity during behavior. This is of critical importance, as abnormal thalamic activity and
disrupted adrenergic signaling are characteristic features of motor diseases. The experiments proposed in this
study will span the mentored K99 and independent R00 phase of this award, with the K99 phase being focused
on defining the activity and role of motor thalamus during motor learning and the R00 phase focused on
understanding how adrenergic input to the thalamus modulates motor signals. My proposed training plan builds
on my experience in two-photon in vivo imaging and mouse behaviors and will add training in slice
electrophysiology. In addition, my expert mentoring team will also provide guidance in my career development
with the goal of launching a successful career as independent investigator at a research institution.
项目摘要
学习和执行运动技能是大脑的重要功能,涉及大脑的协调活动。
多个大脑区域传统上,运动皮层(MCtx),基底神经节(BG)和小脑(CB)
被认为是大脑的关键运动控制区域,这些区域内的可塑性被认为
支持运动学习。此外,神经调节,例如来自蓝斑中的肾上腺素能神经元,
(LC)是正确行为和学习的关键。尽管这些区域在控制
运动及其在运动障碍中的意义,我们才刚刚开始了解运动是如何发生的。
来自这些区域的信号相互作用。从解剖学上讲,丘脑是一个共同的目标
虽然丘脑是MCtx、BG和CB的重要结构,但传统上,丘脑被视为被动中继站。
然而,有新的证据表明,丘脑可以在功能上整合和调节这些不同的,
电机信号丘脑神经元如何对运动输入做出反应,运动丘脑在运动学习中的作用,
以及肾上腺素能信号如何调节丘脑活动在很大程度上是不确定的。我的核心假设是
运动丘脑作为来自MCtx、BG和CB的运动信号的汇聚点,以及
LC的神经调节输入,使其能够在功能上整合这些输入以控制运动,
促进运动学习。我建议使用体内脑深部成像和新型荧光
用于小鼠执行运动任务的细胞内信号传导的传感器以及切片电生理学,
测量运动过程中运动丘脑的活动,并确定这种活动是如何通过
肾上腺素能输入来自LC。这些方法将允许我定义运动丘脑的输入,并测量
运动和运动学习过程中丘脑的活动(目的1),确定运动丘脑的功能作用
及其在运动控制中的输入(目的2),并确定肾上腺素能信号如何调节丘脑活动
在运动学习中(目标3)。这项研究的结果不仅将阐明运动丘脑在
运动控制和运动学习,而且还提供了肾上腺素能神经调节
影响行为过程中的丘脑活动这是至关重要的,因为异常的丘脑活动,
中断的肾上腺素能信号传导是运动疾病的特征性特征。在此提出的实验
该研究将涵盖该奖项的辅导K99和独立R00阶段,重点关注K99阶段
定义运动丘脑在运动学习中的活动和作用,R00阶段侧重于
了解丘脑的肾上腺素输入如何调节运动信号。我提出的训练计划
我在双光子体内成像和小鼠行为方面的经验,并将增加切片培训
电生理学此外,我的专家指导团队也将在我的职业发展方面提供指导
目标是在研究机构作为独立调查员开展成功的职业生涯。
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 }}
Richard Roth其他文献
Richard Roth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 }}
相似海外基金
Preclinical test for the efficacy of adrenergic agents in treatment of AD
肾上腺素能药物治疗AD疗效的临床前试验
- 批准号:
8358448 - 财政年份:2012
- 资助金额:
$ 12.29万 - 项目类别:
Preclinical test for the efficacy of adrenergic agents in treatment of AD
肾上腺素能药物治疗AD疗效的临床前试验
- 批准号:
8517552 - 财政年份:2012
- 资助金额:
$ 12.29万 - 项目类别:
MODULATING FLUID THERAPY WITH ADRENERGIC AGENTS AND CYCLIC AMP ENHANCERS IN
使用肾上腺素能药物和环放大器增强剂调节液体治疗
- 批准号:
7952159 - 财政年份:2009
- 资助金额:
$ 12.29万 - 项目类别:
THE EFFECT OF BETA-ADRENERGIC AGENTS AND FLUID THERAPY IN HUMANS
β-肾上腺素能药物和液体疗法对人体的影响
- 批准号:
7952152 - 财政年份:2009
- 资助金额:
$ 12.29万 - 项目类别:
MODULATING FLUID THERAPY WITH ADRENERGIC AGENTS AND CYCLIC AMP ENHANCERS IN
使用肾上腺素能药物和环放大器增强剂调节液体治疗
- 批准号:
7719194 - 财政年份:2008
- 资助金额:
$ 12.29万 - 项目类别:
THE EFFECT OF BETA-ADRENERGIC AGENTS AND FLUID THERAPY IN HUMANS
β-肾上腺素能药物和液体疗法对人体的影响
- 批准号:
7605416 - 财政年份:2007
- 资助金额:
$ 12.29万 - 项目类别:
MODULATING FLUID THERAPY WITH ADRENERGIC AGENTS AND CYCLIC AMP ENHANCERS IN
使用肾上腺素能药物和环放大器增强剂调节液体治疗
- 批准号:
7605425 - 财政年份:2007
- 资助金额:
$ 12.29万 - 项目类别:
THE EFFECT OF BETA-ADRENERGIC AGENTS AND FLUID THERAPY IN HUMANS
β-肾上腺素能药物和液体疗法对人体的影响
- 批准号:
7378753 - 财政年份:2006
- 资助金额:
$ 12.29万 - 项目类别:
Adrenergic Agents for Methamphetamine: Outpatient Trials
甲基苯丙胺肾上腺素药物:门诊试验
- 批准号:
6825160 - 财政年份:2004
- 资助金额:
$ 12.29万 - 项目类别:
ADRENERGIC AGENTS FOR CARDIOPULMONARY RESUSCITATION
用于心肺复苏的肾上腺素能药物
- 批准号:
2702283 - 财政年份:1997
- 资助金额:
$ 12.29万 - 项目类别: