Netrin-1 mediates stress-induced plasticity of adult pyramidal neurons
Netrin-1 介导应激诱导的成年锥体神经元可塑性
基本信息
- 批准号:RGPIN-2020-04703
- 负责人:
- 金额:$ 4.74万
- 依托单位:
- 依托单位国家:加拿大
- 项目类别:Discovery Grants Program - Individual
- 财政年份:2021
- 资助国家:加拿大
- 起止时间:2021-01-01 至 2022-12-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
During development, the guidance cue receptor, DCC, guides growing axons towards Netrin-1-secreting targets. However, DCC receptors also dictate the fine organization of synaptic connectivity once growing axons have reached their final targets, by controlling axon arborization, dendritic growth and synapse formation. These post-axonal pathfinding processes continue to occur in adulthood and are intimately involved in experience-induced synaptic plasticity. Recent work from our laboratory shows that exposure to chronic social defeat stress in adult male mice results in upregulation of DCC receptor expression in medial prefrontal cortex (mPFC) pyramidal neurons and that this causes susceptibility to develop social avoidance, anhedonia, and anxiety-like behaviors. Knocking out DCC receptors in these neurons prior to stress exposure induces resilience to these effects. How DCC-mediated Netrin-1 signaling in adult pyramidal neurons mediate stress-induced behavioral changes remains to be determined. This proposal is aimed at addressing this question by investigating whether (i) DCC-dependent reorganization of dendritic structure/organization and of spine morphology are involved and (ii) specific neuronal circuits are affected, namely mPFC projections to the nucleus accumbens and/or mPFC projections to the amygdala, two limbic regions involved in motivation and processing of emotional information. To test these ideas, we will continue using a model of chronic social stress in adult male mice and a battery of behavioral tests to measure social interaction, motivation and reward. We will combine these behavioral methods with state-of-the-art anatomical, molecular, and neural recording strategies. In these experiments we will also implement a model of social stress defeat in female mice to begin addressing similar questions in females. This research will provide information, for the first time, about the role of guidance cues in stress-induced plasticity. It will also identify the neural circuitries that are involved in this process.
在发育过程中,引导线索受体DCC引导生长的轴突朝向Netrin-1分泌靶点。然而,DCC受体也通过控制轴突的分枝、树突的生长和突触的形成,在生长的轴突达到最终目标后决定突触连接的精细组织。这些轴突后寻路过程在成年后继续发生,并与经验诱导的突触可塑性密切相关。我们实验室最近的工作表明,成年雄性小鼠暴露在慢性社会失败应激下,会导致内侧前额叶皮质(MPFC)锥体神经元DCC受体表达上调,从而导致容易出现社交回避、快感缺失和焦虑样行为。在应激暴露前敲除这些神经元中的DCC受体可以诱导对这些影响的弹性。DCC介导的成年锥体神经元Netrin-1信号如何介导应激诱导的行为改变仍有待确定。这一建议旨在通过研究是否涉及(I)依赖于DCC的树突结构/组织和脊椎形态的重组以及(Ii)特定的神经元回路是否受到影响,即mPFC投射到伏隔核和/或mPFC投射到杏仁核,这两个边缘区域参与动机和情绪信息的处理。为了测试这些想法,我们将继续使用成年雄性小鼠的慢性社交压力模型和一系列行为测试来衡量社交互动、动机和奖励。我们将把这些行为方法与最先进的解剖学、分子和神经记录策略结合起来。在这些实验中,我们还将在雌性小鼠中实施社会压力失败的模型,以开始在雌性小鼠中解决类似的问题。这项研究将首次提供有关指导线索在应力诱导的可塑性中的作用的信息。它还将识别参与这一过程的神经回路。
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 }}
Flores, Cecilia其他文献
Dopamine Axon Targeting in the Nucleus Accumbens in Adolescence Requires Netrin-1
- DOI:
10.3389/fcell.2020.00487 - 发表时间:
2020-06-25 - 期刊:
- 影响因子:5.5
- 作者:
Cuesta, Santiago;Nouel, Dominique;Flores, Cecilia - 通讯作者:
Flores, Cecilia
Resilience to amphetamine in mouse models of netrin-1 haploinsufficiency: role of mesocortical dopamine
- DOI:
10.1007/s00213-015-4032-9 - 发表时间:
2015-10-01 - 期刊:
- 影响因子:3.4
- 作者:
Pokinko, Matthew;Moquin, Luc;Flores, Cecilia - 通讯作者:
Flores, Cecilia
Early Adolescence is a Critical Period for the Maturation of Inhibitory Behavior
- DOI:
10.1093/cercor/bhy247 - 发表时间:
2019-09-01 - 期刊:
- 影响因子:3.7
- 作者:
Reynolds, Lauren M.;Yetnikoff, Leora;Flores, Cecilia - 通讯作者:
Flores, Cecilia
Awakening the dormant: Role of axonal guidance cues in stress-induced reorganization of the adult prefrontal cortex leading to depression-like behavior.
- DOI:
10.3389/fncir.2023.1113023 - 发表时间:
2023 - 期刊:
- 影响因子:3.5
- 作者:
Mahmud, Ashraf;Avramescu, Radu Gabriel;Niu, Zhipeng;Flores, Cecilia - 通讯作者:
Flores, Cecilia
Axo-glial interactions between midbrain dopamine neurons and oligodendrocyte lineage cells in the anterior corpus callosum.
- DOI:
10.1007/s00429-023-02695-y - 发表时间:
2023-11 - 期刊:
- 影响因子:3.1
- 作者:
Caldwell, Megan;Ayo-Jibunoh, Vanessa;Mendoza, Josue Criollo;Brimblecombe, Katherine R.;Reynolds, Lauren M.;Zhu Jiang, Xin Yan;Alarcon, Colin;Fiore, Elizabeth;N. Tomaio, Jacquelyn;Phillips, Greg R.;Mingote, Susana;Flores, Cecilia;Casaccia, Patrizia;Liu, Jia;Cragg, Stephanie J.;Mccloskey, Dan P.;Yetnikoff, Leora - 通讯作者:
Yetnikoff, Leora
Flores, Cecilia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('Flores, Cecilia', 18)}}的其他基金
Netrin-1 mediates stress-induced plasticity of adult pyramidal neurons
Netrin-1 介导应激诱导的成年锥体神经元可塑性
- 批准号:
RGPIN-2020-04703 - 财政年份:2022
- 资助金额:
$ 4.74万 - 项目类别:
Discovery Grants Program - Individual
Netrin-1 mediates stress-induced plasticity of adult pyramidal neurons
Netrin-1 介导应激诱导的成年锥体神经元可塑性
- 批准号:
RGPIN-2020-04703 - 财政年份:2020
- 资助金额:
$ 4.74万 - 项目类别:
Discovery Grants Program - Individual
Guidance molecules interact to orchestrate dopamine plasticity in adulthood
引导分子相互作用以协调成年期的多巴胺可塑性
- 批准号:
RGPIN-2015-04819 - 财政年份:2019
- 资助金额:
$ 4.74万 - 项目类别:
Discovery Grants Program - Individual
Guidance molecules interact to orchestrate dopamine plasticity in adulthood
引导分子相互作用以协调成年期的多巴胺可塑性
- 批准号:
RGPIN-2015-04819 - 财政年份:2018
- 资助金额:
$ 4.74万 - 项目类别:
Discovery Grants Program - Individual
Guidance molecules interact to orchestrate dopamine plasticity in adulthood
引导分子相互作用以协调成年期的多巴胺可塑性
- 批准号:
RGPIN-2015-04819 - 财政年份:2017
- 资助金额:
$ 4.74万 - 项目类别:
Discovery Grants Program - Individual
Guidance molecules interact to orchestrate dopamine plasticity in adulthood
引导分子相互作用以协调成年期的多巴胺可塑性
- 批准号:
RGPIN-2015-04819 - 财政年份:2016
- 资助金额:
$ 4.74万 - 项目类别:
Discovery Grants Program - Individual
Guidance molecules interact to orchestrate dopamine plasticity in adulthood
引导分子相互作用以协调成年期的多巴胺可塑性
- 批准号:
RGPIN-2015-04819 - 财政年份:2015
- 资助金额:
$ 4.74万 - 项目类别:
Discovery Grants Program - Individual
Mechanisms underlaying drug-induced behavioral sensitization in the adult brain: possible role of guidance cues
成人大脑中药物诱导行为敏感的机制:引导线索的可能作用
- 批准号:
298226-2010 - 财政年份:2014
- 资助金额:
$ 4.74万 - 项目类别:
Discovery Grants Program - Individual
Mechanisms underlaying drug-induced behavioral sensitization in the adult brain: possible role of guidance cues
成人大脑中药物诱导行为敏感的机制:引导线索的可能作用
- 批准号:
298226-2010 - 财政年份:2013
- 资助金额:
$ 4.74万 - 项目类别:
Discovery Grants Program - Individual
Mechanisms underlaying drug-induced behavioral sensitization in the adult brain: possible role of guidance cues
成人大脑中药物诱导行为敏感的机制:引导线索的可能作用
- 批准号:
298226-2010 - 财政年份:2012
- 资助金额:
$ 4.74万 - 项目类别:
Discovery Grants Program - Individual
相似海外基金
Determination of structure-function relationships and role in virulence of a MerR-type regulator that mediates zinc tolerance in Streptococcus mutans
确定介导变形链球菌锌耐受性的 MerR 型调节因子的结构-功能关系及其毒力作用
- 批准号:
10749982 - 财政年份:2023
- 资助金额:
$ 4.74万 - 项目类别:
Adipose tissue mediates cardiac metabolic remodeling in the pathologically stressed heart in the absence of primary metabolic stress
在没有主要代谢应激的情况下,脂肪组织介导病理应激心脏的心脏代谢重塑
- 批准号:
10657015 - 财政年份:2023
- 资助金额:
$ 4.74万 - 项目类别:
Oxytocin Mediates Phasic and Tonic Dopamine Release
催产素介导阶段性和强直性多巴胺释放
- 批准号:
10575856 - 财政年份:2023
- 资助金额:
$ 4.74万 - 项目类别:
Dysregulated cholesterol homeostasis, caused by lysosomal/autophagy dysfunction, mediates pancreatitis
由溶酶体/自噬功能障碍引起的胆固醇稳态失调可介导胰腺炎
- 批准号:
10587086 - 财政年份:2023
- 资助金额:
$ 4.74万 - 项目类别:
CD200 signaling mediates the interactions of neurons and endothelia with circulating leukocytes in stroke
CD200 信号传导介导中风中神经元和内皮细胞与循环白细胞的相互作用
- 批准号:
10737356 - 财政年份:2023
- 资助金额:
$ 4.74万 - 项目类别:
Heterogeneous microglia activation mediates stress-induced changes in neural circuitry.
异质小胶质细胞激活介导应激引起的神经回路变化。
- 批准号:
10741172 - 财政年份:2023
- 资助金额:
$ 4.74万 - 项目类别:
A Long-range Recurrent Neural Network Mediates Threat Induced Innate Sensorimotor Integrations
远程循环神经网络介导威胁诱发的先天感觉运动整合
- 批准号:
10539071 - 财政年份:2022
- 资助金额:
$ 4.74万 - 项目类别:
FAK mediates noise-induced loss of auditory hair cell function and survival
FAK 介导噪声引起的听毛细胞功能和存活的丧失
- 批准号:
10527266 - 财政年份:2022
- 资助金额:
$ 4.74万 - 项目类别:
A Long-range Recurrent Neural Network Mediates Threat Induced Innate Sensorimotor Integrations
远程循环神经网络介导威胁诱发的先天感觉运动整合
- 批准号:
10626968 - 财政年份:2022
- 资助金额:
$ 4.74万 - 项目类别:
Netrin-1 mediates stress-induced plasticity of adult pyramidal neurons
Netrin-1 介导应激诱导的成年锥体神经元可塑性
- 批准号:
RGPIN-2020-04703 - 财政年份:2022
- 资助金额:
$ 4.74万 - 项目类别:
Discovery Grants Program - Individual