HIPPOCAMPAL-PREFRONTAL SYNCHRONY IN WORKING MEMORY
工作记忆中的海马-前额同步
基本信息
- 批准号:8760388
- 负责人:
- 金额:$ 37.6万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2014
- 资助国家:美国
- 起止时间:2014-07-11 至 2019-05-31
- 项目状态:已结题
- 来源:
- 关键词:Action PotentialsAddressAffectAnimalsBehaviorBehavioralCationsChloride IonChloridesCodeCommunicationConfounding Factors (Epidemiology)DataDiscriminationDiseaseExhibitsFrequenciesFundingGeneralized Anxiety DisorderGoalsHippocampus (Brain)ImpairmentLaboratoriesLeadLeftLightMajor Depressive DisorderMeasuresMemoryMemory impairmentMethodsMidline Thalamic NucleiMotivationMotorNeuronsNeurosciencesPatternPerformancePhasePhysiologicalPrefrontal CortexPublishingPumpResearchRewardsRoleSchizophreniaSensoryShort-Term MemorySiteTask PerformancesTechniquesTestingTheta RhythmTimeUpdateWorkbasecognitive functiondesignimprovedmemory processneuromechanismneurophysiologyneuropsychiatryoptogeneticspublic health relevancerelating to nervous systemresearch studyresponsetherapeutic developmenttool
项目摘要
DESCRIPTION (provided by applicant): Despite decades of research, the neural mechanisms of working memory, the ability to hold information over a temporal delay to guide goal-directed behavior, remain poorly understood. Although oscillatory synchrony between the hippocampus (HC) and the prefrontal cortex (PFC) is known to increase in situations of high working memory demand, the mechanisms and circuitry supporting HC-PFC interactions during working memory is unknown. The midline thalamic nucleus reuniens (RE) is reciprocally connected to both the HC and the PFC and has been shown to be critical for working memory tasks. Therefore, the guiding hypothesis of the current proposal is that HC-PFC oscillatory synchrony is regulated by the RE. If this hypothesis is true, when working memory demand is high, RE should drive HC-PFC oscillatory synchrony, giving rise to relatively higher HC-PFC theta coherence and stronger PFC phase-locking to the hippocampal theta rhythm. Similarly, suppression of RE activity should yield reduced HC-PFC oscillatory synchrony and lead to working memory impairments. We have shown that hippocampal neurons exhibit different patterns of spatial coding in response to manipulation of working memory demand. New published data from our lab demonstrate that RE inactivation selectively impairs a working memory task, leaving a very similar, but non-working memory, task unchanged. Additional preliminary data show that HC-PFC oscillatory synchrony is also modulated by working memory demand. The proposed studies will use a combination of electrophysiological methods, bidirectional optogenetic manipulation of neuronal excitation, and behavior to address the following questions (1) Does RE inactivation reduce hippocampal-PFC synchrony and concomitantly impair working memory? (2) Does RE activation increase HC-PFC synchrony and concomitantly improve working memory? (3) Does RE show increased oscillatory synchrony with the HC and PFC during working memory task performance? If funded, the proposed work will have a significant impact on memory research and on the field of neuroscience by advancing the basic understanding of the circuit-level interactions between the HC, RE and PFC. More broadly, the proposal will advance the understanding of the neural mechanisms underlying working memory by uncovering the mechanisms underlying HC-PFC oscillatory synchrony. Moreover, by pioneering RE recordings during memory-guided behavior, we will not only characterize RE behavioral correlates for the first time, but also identify the role of the RE in regulating functinal interactions between the HC and the PFC. Finally, we will be the first to use optogenetic methods to manipulate the activity of the RE and measure the effects on memory-guided behavior as well as on HC-PFC synchrony. Although optogenetic methods are becoming more widely used, the studies proposed here will advance the use of this state-of-the-art technique as a tool for understanding circuits and mechanisms underlying higher cognitive functions.
描述(由申请人提供):尽管经过几十年的研究,工作记忆的神经机制,即在一段时间内保持信息以指导目标导向行为的能力,仍然知之甚少。虽然海马体(HC)和前额叶皮质(PFC)之间的振荡同步在工作记忆需求高的情况下会增加,但在工作记忆中支持HC-PFC相互作用的机制和电路尚不清楚。丘脑中线再合核(RE)与HC和PFC相互连接,并已被证明对工作记忆任务至关重要。因此,本研究的指导假设是HC-PFC的振荡同步受RE的调节。如果该假设成立,当工作记忆需求高时,RE会驱动HC-PFC的振荡同步,导致HC-PFC的θ相干性相对较高,PFC对海马θ节律的锁相性较强。同样,抑制RE活动会导致HC-PFC振荡同步减少,并导致工作记忆受损。我们已经证明海马神经元在工作记忆需求的操纵下表现出不同的空间编码模式。我们实验室最新公布的数据表明,RE失活选择性地损害了工作记忆任务,使非常相似的非工作记忆任务保持不变。另外的初步数据表明,HC-PFC振荡同步也受到工作记忆需求的调节。拟议的研究将结合电生理方法、双向光遗传学操作神经元兴奋和行为来解决以下问题:(1)RE失活是否会减少海马- pfc同步并随之损害工作记忆?(2) RE激活是否增加了HC-PFC的同步性并随之改善了工作记忆?(3)在工作记忆任务执行过程中,反射区是否表现出与HC和PFC增强的振荡同步性?如果获得资助,该研究将对记忆研究和神经科学领域产生重大影响,促进对HC、RE和pfc之间回路水平相互作用的基本理解。更广泛地说,该研究将通过揭示HC- pfc振荡同步的机制,促进对工作记忆的神经机制的理解。此外,通过在记忆引导行为中开创性地记录RE,我们不仅将首次表征RE行为相关性,而且还将确定RE在调节HC和pfc之间功能相互作用中的作用。最后,我们将首次使用光遗传学方法来操纵RE的活动,并测量其对记忆引导行为以及HC- pfc同步的影响。尽管光遗传学方法正得到越来越广泛的应用,但本文提出的研究将推动这一最先进技术的使用,作为理解高级认知功能背后的电路和机制的工具。
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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Amy L. Griffin其他文献
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- DOI:
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2023 - 期刊:
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GeoAI 中的制图:新兴主题和研究挑战
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- 发表时间:
2023 - 期刊:
- 影响因子:0
- 作者:
A. Robinson;A. Çöltekin;Amy L. Griffin;Florian Ledermann - 通讯作者:
Florian Ledermann
Amy L. Griffin的其他文献
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{{ truncateString('Amy L. Griffin', 18)}}的其他基金
Using hippocampal-prefrontal theta synchrony to enhance spatial working memory
利用海马-前额叶θ同步增强空间工作记忆
- 批准号:
9752196 - 财政年份:2019
- 资助金额:
$ 37.6万 - 项目类别:
HIPPOCAMPAL-PREFRONTAL SYNCHRONY IN WORKING MEMORY
工作记忆中的海马-前额同步
- 批准号:
9247806 - 财政年份:2014
- 资助金额:
$ 37.6万 - 项目类别:
Delaware Clinical and Translational Research ACCEL Program (Professional Development Core)
特拉华州临床和转化研究 ACCEL 计划(专业发展核心)
- 批准号:
10721014 - 财政年份:2013
- 资助金额:
$ 37.6万 - 项目类别:
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