Glutamate receptor signaling pathways in the circuit integration of adult-born neurons
成人神经元电路整合中的谷氨酸受体信号通路
基本信息
- 批准号:10613431
- 负责人:
- 金额:$ 44.18万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-08-01 至 2025-04-30
- 项目状态:未结题
- 来源:
- 关键词:AblationAccelerationAdultAffectAffectiveAge-Related Memory DisordersAlzheimer&aposs DiseaseAnimalsArray tomographyBehaviorBrainCell MaturationCellsChloridesDevelopmental ProcessEpisodic memoryEquilibriumFamilyGenesGenetic RecombinationGlutamate ReceptorGoalsHeadHippocampusImageImpairmentInterneuronsKainic Acid ReceptorsLearningLinkMapsMemoryMicroscopeModelingMolecularMolecular ProfilingMood DisordersMusNeurodegenerative DisordersNeuronsPatternPhasePlayPost-Traumatic Stress DisordersProcessPropertyReceptor SignalingResolutionRetrievalRoleSchizophreniaSignal PathwaySignal TransductionSpace PerceptionSynapsesSynaptic plasticityTestingadult neurogenesisbehavior measurementconditional knockoutdentate gyrusexperimental studygamma-Aminobutyric Acidgranule cellin vivoinsightmemory processmicroendoscopenerve stem cellnervous system disorderneural circuitneural correlateneuropsychiatric disordernewborn neuronnormal agingnovelnovel therapeuticsoptogeneticssingle cell analysisspatiotemporalsymportertooltranscriptometransmission process
项目摘要
Adult neurogenesis in the hippocampus occurs in the well-defined neurogenic niche in the subgranular zone of
the dentate gyrus. Newborn neurons are continuously generated and mature over the course of weeks to
integrate into the hippocampal circuit. Adult-born immature dentate gyrus cells (DGCs) have unique functional
properties that give them a privileged role in circuits that define specific behaviors, and which are critical to
episodic memory formation and retrieval. In particular these neurons play important roles in an animal’s ability
to separate similar patterns and disambiguate overlapping memories, processes that become impaired during
normal aging and in neurodegenerative and neuropsychiatric disorders. Therefore, mechanisms that regulate
adult-born DGC maturation and integration are important in understanding diverse neurological disorders
including Alzheimer’s disease, schizophrenia and post-traumatic stress disorders. Kainate receptors are a
class of glutamate receptor whose contributions to heterogeneous synaptic processes are still not fully
understood. The premise of these studies is built upon foundational studies in which we discovered that the
maturation of adult-born DGCs is more rapid after ablation of kainate receptors. We found that this effect was
likely through a disruption of intracellular Cl- gradient because of an effect on a neuronal Cl- transporter. We
will fully describe the altered molecular, synaptic, and functional alterations after loss of kainate receptor
signaling and will test whether GABA disruption is causal to the altered integration of maturating DGCs into the
hippocampal circuit. We will determine how altered maturation of adult-born DGCs affects the animal’s ability
to discriminate between similar patterns and temporal overlap of episodic memories and using in vivo
microendoscope imaging correlate cellular activity to behavioral measurements in a pattern separation task.
The goal of this project is to examine a new mechanism by which glutamate receptors affect adult-born DGC
integration by modulating GABA signaling. These studies would define novel processes that regulate adult-born neurons that could underlie the known involvement of kainate receptor signaling in mechanisms of
learning and memory.
海马的成年神经发生发生在海马颗粒下区的明确的神经发生龛中。
齿状回新生神经元在数周内不断产生和成熟,
整合到海马电路中。成年出生的未成熟齿状回细胞(DGC)具有独特的功能,
在定义特定行为的电路中赋予它们特权角色的特性,以及对
情景记忆的形成和提取特别是这些神经元在动物的能力中起着重要的作用
为了分离相似的模式并消除重叠的记忆,
正常衰老以及神经变性和神经精神障碍。因此,调控机制
成人出生的DGC成熟和整合在理解各种神经系统疾病中很重要
包括老年痴呆症、精神分裂症和创伤后应激障碍。红藻氨酸受体是一种
一类谷氨酸受体,其对异质性突触过程的贡献仍不完全
明白这些研究的前提是建立在基础研究的基础上,我们发现,
在去除红藻氨酸受体后,成人出生的DGC的成熟更快。我们发现这种效应
可能是由于对神经元Cl-转运体的影响而破坏细胞内Cl-梯度。我们
将充分描述红藻氨酸受体丧失后分子、突触和功能的改变
信号传导,并将测试GABA破坏是否是成熟DGC整合到细胞中的改变的原因。
海马回路我们将确定成年DGC成熟的改变如何影响动物的能力,
区分情节记忆的相似模式和时间重叠,并在体内使用
显微内窥镜成像将细胞活性与模式分离任务中的行为测量相关联。
本项目的目标是研究谷氨酸受体影响成人DGC的新机制
通过调节GABA信号整合。这些研究将定义调节成年出生的神经元的新过程,这些过程可能是已知的红藻氨酸受体信号传导参与神经元凋亡机制的基础。
学习和记忆。
项目成果
期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
A Pathogenic Missense Mutation in Kainate Receptors Elevates Dendritic Excitability and Synaptic Integration through Dysregulation of SK Channels.
红藻氨酸受体中的致病性错义突变通过 SK 通道失调来提高树突兴奋性和突触整合。
- DOI:10.1523/jneurosci.1259-23.2023
- 发表时间:2023
- 期刊:
- 影响因子:0
- 作者:Nomura,Toshihiro;Taniguchi,Sakiko;Wang,Yi-Zhi;Yeh,Nai-Hsing;Wilen,AnikaP;Castillon,CharlotteCM;Foote,KendallM;Xu,Jian;Armstrong,JohnN;Savas,JeffreyN;Swanson,GeoffreyT;Contractor,Anis
- 通讯作者:Contractor,Anis
Recruitment of parvalbumin and somatostatin interneuron inputs to adult born dentate granule neurons.
- DOI:10.1038/s41598-020-74385-2
- 发表时间:2020-10-16
- 期刊:
- 影响因子:4.6
- 作者:Remmers CL;Castillon CCM;Armstrong JN;Contractor A
- 通讯作者:Contractor A
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{{ truncateString('Anis Contractor', 18)}}的其他基金
Regulation of kainate receptor expression in cone bipolar cells
视锥双极细胞中红藻氨酸受体表达的调节
- 批准号:
10367733 - 财政年份:2022
- 资助金额:
$ 44.18万 - 项目类别:
Effectors of presynaptic cAMP dependent potentiation at mossy fiber synapses
苔藓纤维突触突触前 cAMP 依赖性增强的效应器
- 批准号:
10501884 - 财政年份:2022
- 资助金额:
$ 44.18万 - 项目类别:
Effectors of presynaptic cAMP dependent potentiation at mossy fiber synapses
苔藓纤维突触突触前 cAMP 依赖性增强的效应器
- 批准号:
10674994 - 财政年份:2022
- 资助金额:
$ 44.18万 - 项目类别:
Effectors of presynaptic cAMP dependent potentiation at mossy fiber synapses_Diversity Supplement
苔藓纤维突触突触前 cAMP 依赖性增强效应器_Diversity Supplement
- 批准号:
10810245 - 财政年份:2022
- 资助金额:
$ 44.18万 - 项目类别:
Cortical Interneuron Dysfunction in Fragile X Syndrome
脆性 X 综合征中的皮质中间神经元功能障碍
- 批准号:
10599332 - 财政年份:2022
- 资助金额:
$ 44.18万 - 项目类别:
Cortical Interneuron Dysfunction in Fragile X Syndrome
脆性 X 综合征中的皮质中间神经元功能障碍
- 批准号:
10418431 - 财政年份:2022
- 资助金额:
$ 44.18万 - 项目类别:
Regulation of kainate receptor expression in cone bipolar cells
视锥双极细胞中红藻氨酸受体表达的调节
- 批准号:
10706972 - 财政年份:2022
- 资助金额:
$ 44.18万 - 项目类别:
Glutamate receptor signaling pathways in the circuit integration of adult-born neurons
成人神经元电路整合中的谷氨酸受体信号通路
- 批准号:
10393032 - 财政年份:2020
- 资助金额:
$ 44.18万 - 项目类别:
Mechanisms of cAMP dependent potentiation of mossy fiber synapses
苔藓纤维突触 cAMP 依赖性增强机制
- 批准号:
10201932 - 财政年份:2020
- 资助金额:
$ 44.18万 - 项目类别:
Glutamate receptor signaling pathways in the circuit integration of adult-born neurons
成人神经元电路整合中的谷氨酸受体信号通路
- 批准号:
10219367 - 财政年份:2020
- 资助金额:
$ 44.18万 - 项目类别:
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