Prefrontal neural modulation to restore cognitive deficits in an Alzheimer's Disease rat model
前额神经调节可恢复阿尔茨海默病大鼠模型的认知缺陷
基本信息
- 批准号:10373174
- 负责人:
- 金额:$ 41.23万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-02-15 至 2025-01-31
- 项目状态:未结题
- 来源:
- 关键词:AffectAlzheimer disease screeningAlzheimer&aposs DiseaseAlzheimer&aposs disease pathologyAlzheimer&aposs disease patientAlzheimer&aposs disease riskAmyloidAmyloid beta-ProteinAttentionBehaviorBehavioralBrainCognitiveCognitive deficitsComplexDecision MakingDorsalExhibitsFaceFrequenciesFunctional disorderFutureGoalsHippocampus (Brain)HumanHuman Amyloid Precursor ProteinImpairmentLeadLinkMeasuresMedialMediatingMemoryMemory LossMemory impairmentModelingNeurofibrillary TanglesNeuronal DysfunctionNeuronal InjuryNeuronsNeurophysiology - biologic functionPathologyPatientsPositioning AttributePredispositionPrefrontal CortexProcessProtocols documentationQuality of lifeRattusReversal LearningRewardsRodentShort-Term MemoryTemporal LobeTestingTransgenic Organismsage relatedbehavior changebehavioral impairmentcognitive controlcognitive functioncognitive processcognitive taskflexibilityfrontal lobegray matterimprovedin vivoloss of functionmemory processmutantneural circuitneuroinflammationneuropathologyneurophysiologyneuroregulationnoninvasive brain stimulationoverexpressionpresenilin-1relating to nervous systemresponsetau Proteinstherapeutic target
项目摘要
Project Summary
Alzheimer’s disease (AD) is characterized by memory impairments and underlying neuropathology, including
plaques, amyloid-β peptides, tau, in conjunction with neuroinflammation, and neuronal injury/loss, particularly in
the medial temporal lobe. Recent studies, however, suggest neurophysiological alterations in the prefrontal
cortex (PFC) evident in AD patients prior to gross neuropathology which may contribute to deficits in cognitive
processing early in AD. Given that the PFC contributes to top-down control of memory processing necessary
for optimal decision-making, dysfunction within the PFC may contribute to suboptimal decision-making which
often precedes gross memory loss in AD patients. Optimal decision-making requires functioning working memory
processes (i.e., using information “online” to guide choices) and flexible behavior (the ability to shift behavior in
response to changing consequences). Critically, early-stage AD may target brain circuits that underlie these
prefrontal dependent processes leading to early impairment in optimal cognitive processing. As such,
understanding neural circuits that are affected in AD underlie complex cognitive deficits may lead to earlier and
effective screening for AD risk and serve as an important therapeutic target for improving the quality of life AD
patients. The rat prelimbic cortex (PrL) is heavily implicated in working memory and flexible behavior necessary
for online decision-making. AD rats that were developed to show age-dependent neuropathological signatures
(plaques, tau) consistent with AD are impaired in PrL-dependent cognitive tasks prior to accumulation of
neuropathology. Critically, these deficits in PrL-dependent tasks precede behavioral deficits in other memory
tasks that do not depend on PrL function. As such, targeting the PrL function in vivo may restore these cognitive
processes in the AD rat model. Here, we aim to use noninvasive brain stimulation that modulates neural
oscillations to restore PrL-hippocampal neural activity (Aim 1) and PrL-orbitofrontal cortex neural activity (Aim 2)
in working memory (delay nonmatch to position task) and flexible behavior (reversal learning), respectively.
项目摘要
阿尔茨海默病(AD)的特征在于记忆障碍和潜在的神经病理学,包括
斑块、淀粉样蛋白-β肽、tau蛋白,与神经炎症和神经元损伤/丧失相关,特别是在
内侧颞叶然而,最近的研究表明,前额叶的神经生理学改变,
在AD患者中,在大体神经病理学之前明显存在皮质(PFC),这可能导致认知功能缺陷
在AD早期处理。鉴于PFC有助于自上而下控制记忆处理的必要性,
对于最佳决策,前额叶皮层功能障碍可能导致次优决策,
通常在AD患者出现严重记忆丧失之前出现。最佳决策需要工作记忆
过程(即,使用“在线”信息来指导选择)和灵活的行为(在
改变的后果)。至关重要的是,早期AD可能会针对这些疾病背后的大脑回路
前额叶依赖性过程导致最佳认知过程的早期损伤。因此,在本发明的一个方面,
了解在AD中受影响的神经回路是复杂认知缺陷的基础,
有效筛查AD风险并作为改善AD生活质量的重要治疗靶点
患者大鼠前边缘皮层(PrL)与工作记忆和灵活行为密切相关
在线决策。显示年龄依赖性神经病理学特征的AD大鼠
与AD一致的斑块(tau蛋白)在PRL依赖性认知任务中受损,
神经病理学关键的是,这些缺陷在PRL依赖的任务之前的行为缺陷,在其他记忆
不依赖于PrL功能的任务。因此,在体内靶向PrL功能可以恢复这些认知功能。
在AD大鼠模型中的过程。在这里,我们的目标是使用非侵入性脑刺激,
振荡以恢复PrL-海马神经活动(Aim 1)和PrL-眶额皮质神经活动(Aim 2)
在工作记忆(延迟不匹配位置任务)和灵活行为(反向学习)。
项目成果
期刊论文数量(1)
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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{{ truncateString('Elizabeth A West', 18)}}的其他基金
NEURAL CIRCUITRY MEDIATING BEHAVIORAL FLEXIBILITY
神经回路调节行为灵活性
- 批准号:
10055804 - 财政年份:2020
- 资助金额:
$ 41.23万 - 项目类别:
B1 noradrenergic blockade in early withdrawal to reduce cocaine induced behavioral flexibility deficit
早期戒断时 B1 去甲肾上腺素能阻断可减少可卡因引起的行为灵活性缺陷
- 批准号:
10550086 - 财政年份:2020
- 资助金额:
$ 41.23万 - 项目类别:
NEURAL CIRCUITRY MEDIATING BEHAVIORAL FLEXIBILITY
神经回路调节行为灵活性
- 批准号:
10363725 - 财政年份:2020
- 资助金额:
$ 41.23万 - 项目类别:
Neural circuitry mediating behavioral flexibility
调节行为灵活性的神经回路
- 批准号:
9385375 - 财政年份:2017
- 资助金额:
$ 41.23万 - 项目类别:
Neural circuitry mediating behavioral flexibility
调节行为灵活性的神经回路
- 批准号:
9548189 - 财政年份:2017
- 资助金额:
$ 41.23万 - 项目类别:
NEURAL CIRCUITRY MEDIATING BEHAVIORAL FLEXIBILITY
神经回路调节行为灵活性
- 批准号:
10121211 - 财政年份:2017
- 资助金额:
$ 41.23万 - 项目类别:
The role of accumbens neural activity and dopamine release in flexible behavior
伏隔核神经活动和多巴胺释放在灵活行为中的作用
- 批准号:
8914958 - 财政年份:2014
- 资助金额:
$ 41.23万 - 项目类别:
The role of the orbitofrontal cortex in goal-directed behavior
眶额皮质在目标导向行为中的作用
- 批准号:
8063317 - 财政年份:2011
- 资助金额:
$ 41.23万 - 项目类别: