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

基本信息

  • 批准号:
    10674994
  • 负责人:
  • 金额:
    $ 63.84万
  • 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:
    2022-08-01 至 2027-07-31
  • 项目状态:
    未结题

项目摘要

SUMMARY Synaptic plasticity in the hippocampus is critical to the formation, storage and retrieval of episodic memories. The separate regions of the hippocampus have evolved to play distinct roles in spatial navigation, contextual memories, social memories, and our ability to separate patterns or complete patterns to reconstruct partial memories. In particular the dentate and CA3 regions of the hippocampus are involved in pattern separation that is vital to the integrity of episodic memories. At the center of this region are the mossy fiber afferents that make conditional detonator synapses onto CA3 pyramidal neurons, which have a distinct form of presynaptic cAMP dependent plasticity. Despite the importance of cAMP plasticity to memory formation and retrieval in the CA3 the exact molecular mechanisms underlying MF LTP have yet to be uncovered. The premise of this research builds upon our finding that there are at least two downstream cAMP effectors, PKA (protein kinase A) and Epac2 (exchange protein directly activated by cAMP 2), that contribute to cAMP dependent MF LTP. Despite these findings it is still not known how signaling by each of these effectors results in elevated release from MF synapses and, what are the important targets and substrates that are involved in MF LTP. Here we will use a comprehensive approach with leading edge proteomic, biochemical and electrophysiological approaches to determine the signaling partners of the cAMP effectors, and uncover the physiological mechanism of their actions. Thus, in Aim 1 we will take orthogonal approaches to find the interactors and substrates of PKA and Epac2 and validate these by performing high resolution labeling in situ. In Aim 2 we will determine the exact physiological mechanism that underlie increases in release of neurotransmitter at MF synapses using a combined optoactivation-knockout/pharmacological strategy. In the final Aim we will answer the question of how these different, but convergent, mechanisms are engaged during naturalistic activity patterns, and whether selective disruption of these effectors impairs the ability of mice to separate similar patterns that underlie the formation and retrieval of episodic memories.
总结

项目成果

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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:
    $ 63.84万
  • 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:
    $ 63.84万
  • 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:
    $ 63.84万
  • 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:
    $ 63.84万
  • 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:
    $ 63.84万
  • 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:
    $ 63.84万
  • 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:
    $ 63.84万
  • 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:
    10613431
  • 财政年份:
    2020
  • 资助金额:
    $ 63.84万
  • 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:
    $ 63.84万
  • 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:
    $ 63.84万
  • 项目类别:
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