Presynaptic Modulation of Synaptic Inhibition onto Hippocampal Pyramidal Neurons

海马锥体神经元突触抑制的突触前调节

基本信息

项目摘要

PROJECT SUMMARY Throughout the hippocampus, pyramidal cells integrate excitatory and inhibitory inputs from a diverse population of interneurons. These cells provide feedforward and feedback inhibition onto CA1 pyramidal cells, and can be recruited via glutamate spillover, a phenomenon that describes non-synaptic actions of glutamate diffusing away from the synaptic cleft. The current prevailing view is that glutamate spillover leads to activation of presynaptic group III metabotropic (mGluRIII) glutamate receptors, which inhibit synaptic excitation and inhibition only onto interneurons, not CA1 pyramidal cells. Against this interpretation, our preliminary data indicates that spillover activation of mGluRIII receptors also exists at inhibitory synapses formed onto CA1 pyramidal cells. The main goals in this application are: (i) to determine how mGluRIII activation via glutamate spillover varies between excitatory and inhibitory inputs, and among inhibitory inputs formed by different classes of interneurons; (ii) to identify the intracellular signaling mechanisms that couple mGluRIII activation to neurotransmitter release; (iii) the determine the sub-cellular location of different type of mGluRIII receptors at different types of inhibitory synapses onto CA1 pyramidal cells; (iv) to determine how spillover activation of mGluRIII alters encoding of spatial information by hippocampal CA1 place cells in vivo. The proposed experiments capitalize on in vitro and in vivo electrophysiology, and EM approaches. These findings will generate new information on the operating principles of neuronal circuits involved in spatial map representation and will contribute to the future development of effective strategies to treat disease states associated with hippocampal neural circuit dysfunction, like epilepsy and autism spectrum disorder.
项目总结 在整个海马区,锥体细胞整合来自不同来源的兴奋性和抑制性输入 中间神经元的数量。这些细胞对CA1锥体细胞提供前馈和反馈抑制, 并且可以通过谷氨酸溢出来招募,谷氨酸溢出是一种描述谷氨酸的非突触行为的现象 从突触裂隙扩散开来。目前流行的观点是谷氨酸溢出导致激活 突触前III组代谢性(MGluRIII)谷氨酸受体,它抑制突触兴奋和 仅对中间神经元有抑制作用,对CA1锥体细胞无抑制作用。与这种解释相反,我们的初步数据 提示在CA1上形成的抑制性突触上也存在mGluRIII受体的溢出激活 锥体细胞。本申请的主要目标是:(I)确定mGluRIII是如何通过谷氨酸激活的 兴奋性输入和抑制性输入之间以及不同类别形成的抑制性输入之间的溢出效应不同 (Ii)确定将mGluRIII激活偶联到 神经递质释放;(Iii)确定不同类型mGluRIII受体的亚细胞位置 不同类型的抑制性突触连接到CA1锥体细胞;(Iv)确定外溢激活如何 MGluRIII改变了体内海马CA1区细胞对空间信息的编码。建议数 实验利用了体外和体内的电生理学和EM方法。这些发现将产生 关于参与空间地图表示和意志的神经元电路工作原理的新信息 有助于未来制定有效的策略来治疗与海马体相关的疾病状态 神经回路功能障碍,如癫痫和自闭症谱系障碍。

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 }}

Annalisa Scimemi其他文献

Annalisa Scimemi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 }}

{{ truncateString('Annalisa Scimemi', 18)}}的其他基金

Astrocyte remodeling during the sleep/wake cycle
睡眠/觉醒周期期间星形胶质细胞的重塑
  • 批准号:
    9374291
  • 财政年份:
    2017
  • 资助金额:
    $ 46.11万
  • 项目类别:

相似国自然基金

层出镰刀菌氮代谢调控因子AreA 介导伏马菌素 FB1 生物合成的作用机理
  • 批准号:
    2021JJ40433
  • 批准年份:
    2021
  • 资助金额:
    0.0 万元
  • 项目类别:
    省市级项目
寄主诱导梢腐病菌AreA和CYP51基因沉默增强甘蔗抗病性机制解析
  • 批准号:
    32001603
  • 批准年份:
    2020
  • 资助金额:
    24.0 万元
  • 项目类别:
    青年科学基金项目
AREA国际经济模型的移植.改进和应用
  • 批准号:
    18870435
  • 批准年份:
    1988
  • 资助金额:
    2.0 万元
  • 项目类别:
    面上项目

相似海外基金

Role of Central Neurotensin Signaling in the Ventral Tegmental Area for Ingestive Behavior and Body Weight
中枢神经降压素信号在腹侧被盖区对摄入行为和体重的作用
  • 批准号:
    10536558
  • 财政年份:
    2022
  • 资助金额:
    $ 46.11万
  • 项目类别:
Role of Central Neurotensin Signaling in the Ventral Tegmental Area for Ingestive Behavior and Body Weight
中枢神经降压素信号在腹侧被盖区对摄入行为和体重的作用
  • 批准号:
    10665597
  • 财政年份:
    2022
  • 资助金额:
    $ 46.11万
  • 项目类别:
Elucidation of the functional role of neural stem cells in the area postrema in the regulation of feeding behavior
阐明后区神经干细胞在调节摄食行为中的功能作用
  • 批准号:
    21K15177
  • 财政年份:
    2021
  • 资助金额:
    $ 46.11万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
Evaluation Analysis of Networked Compact City Considering the Wandering Behavior in the Urban Function and Residential guidance Area.
考虑城市功能与居住引导区游走行为的网络化紧凑城市评价分析。
  • 批准号:
    21K04296
  • 财政年份:
    2021
  • 资助金额:
    $ 46.11万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
What is the origin of friction force depending on the sliding velocity? Approach from atomic-scale behavior in real area of contact
取决于滑动速度的摩擦力的来源是什么?
  • 批准号:
    20K04115
  • 财政年份:
    2020
  • 资助金额:
    $ 46.11万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Defining the differential roles of Glutamatergic and GABAergic projections from the Lateral Preoptic Area to the Lateral Habenula in Reward, Aversion, and Drug-Seeking Behavior.
定义从外侧视前区到外侧缰核的谷氨酸能和 GABA 能投射在奖励、厌恶和药物寻求行为中的不同作用。
  • 批准号:
    10242872
  • 财政年份:
    2019
  • 资助金额:
    $ 46.11万
  • 项目类别:
Elucidating roles of ventral tegmental area dopaminergic neurons in motivation of appetitive goal-directed behavior
阐明腹侧被盖区多巴胺能神经元在食欲目标导向行为的激励中的作用
  • 批准号:
    19K03381
  • 财政年份:
    2019
  • 资助金额:
    $ 46.11万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Defining the differential roles of Glutamatergic and GABAergic projections from the Lateral Preoptic Area to the Lateral Habenula in Reward, Aversion, and Drug-Seeking Behavior.
定义从外侧视前区到外侧缰核的谷氨酸能和 GABA 能投射在奖励、厌恶和药物寻求行为中的不同作用。
  • 批准号:
    9926602
  • 财政年份:
    2019
  • 资助金额:
    $ 46.11万
  • 项目类别:
Investigating the interplay between ventral tegmental area dopamine, medial orbitofrontal cortex, and ventromedial striatum in compulsive-like behavior
研究强迫样行为中腹侧被盖区多巴胺、内侧眶额皮质和腹内侧纹状体之间的相互作用
  • 批准号:
    9393053
  • 财政年份:
    2018
  • 资助金额:
    $ 46.11万
  • 项目类别:
Role of Lateral Hypothalmic Area Perineuronal Nets in the Reinstatement of Cocaine-Seeking Behavior
外侧下丘脑区神经周围网络在恢复可卡因寻求行为中的作用
  • 批准号:
    9598308
  • 财政年份:
    2018
  • 资助金额:
    $ 46.11万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了