Role of GABAergic inhibition in the hippocampal contribution to stress susceptibility
GABA 能抑制在海马应激易感性贡献中的作用
基本信息
- 批准号:RGPIN-2021-03739
- 负责人:
- 金额:$ 2.91万
- 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:2022
- 资助国家:加拿大
- 起止时间:2022-01-01 至 2023-12-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
A fundamental question in the field of stress neurobiology is why we respond to stress differently. Investigating the biological mechanism of individual differences in stress susceptibility has important implications for the impact of stress on memory. One of the brain regions that is imperative for stress susceptibility is the hippocampus. The hippocampus not only is well-known for its roles in memory, but also is highly sensitive to stress. Although stress susceptibility has been associated with high hippocampal activity, mechanisms underlying this hippocampal change remain unclear. The long-term goal of this research program is to investigate the role of hippocampal GABAergic inhibition in stress susceptibility. Hippocampal activity is regulated by the balance between excitatory and inhibitory synaptic transmission. Apart from neural inhibition, activity of GABAergic neurons is crucial for the processing of sensory information for memory formation. Since GABAergic inhibition is highly sensitive to stress, we hypothesize that stress susceptibility is regulated by the activity of GABAergic neurons in the hippocampus. Our short-term goal is to examine changes in the functional property of two types of GABAergic interneurons: parvalbumin- (PV neurons) and somatostatin-expressing neurons (SOM neurons) in mice that are either susceptible or resilient to chronic social defeat stress. In the first objective, we will use in vitro techniques to examine changes in GABAergic inhibition in mice with different stress susceptibilities. We will first use electrophysiology to examine changes in synaptic transmission in these mice. Next, we will study the excitability of and synaptic inputs onto PV and SOM neurons in mice with different stress susceptibilities. We will also examine if modulating PV or SOM neuronal activity by optogenetic approaches rescues the reduction of GABAergic transmission in susceptible mice. Finally, we will investigate if changes in GABAergic transmission are responsible for the higher stress susceptibility in female mice. In the second objective, we will use the UCLA miniscope to monitor PV and SOM neuronal activity in freely moving mice. Changes in the activity of these neurons will be examined before, during and after chronic social defeat stress in mice that are either susceptible or resilient to this stressor. We will also use the chemogenetic technique to study the effect of modulating PV or SOM neuronal activity on stress susceptibility. This research program will advance our understanding of how stress susceptibility is regulated by hippocampal GABAergic neurons. Our findings will also reveal how these GABAergic interneurons contribute to the processing of repeated aversive experiences, a mechanism that underlies the impact of chronic stress on memory.
压力神经生物学领域的一个基本问题是,为什么我们对压力的反应不同。研究应激易感性个体差异的生物学机制对应激对记忆的影响具有重要意义。海马体是大脑中对压力敏感性至关重要的区域之一。海马体不仅因其在记忆中的作用而闻名,而且对压力高度敏感。尽管应激易感性与高海马活动有关,但这种海马变化的机制尚不清楚。本研究计划的长期目标是研究海马gaba能抑制在应激易感性中的作用。海马活动是由兴奋性和抑制性突触传递之间的平衡调节的。除了神经抑制外,gaba能神经元的活动对记忆形成的感觉信息加工至关重要。由于GABAergic抑制对应激高度敏感,我们假设应激敏感性是由海马GABAergic神经元的活性调节的。我们的短期目标是研究两种gaba能中间神经元的功能特性变化:小白蛋白神经元(PV神经元)和生长抑素表达神经元(SOM神经元),这些神经元对慢性社会失败压力敏感或有弹性。在第一个目标中,我们将使用体外技术来检查具有不同应激敏感性的小鼠中gaba能抑制的变化。我们将首先使用电生理学来检查这些小鼠突触传递的变化。接下来,我们将研究不同应激敏感性小鼠PV和SOM神经元的兴奋性和突触输入。我们还将研究通过光遗传学方法调节PV或SOM神经元活动是否有助于减少易感小鼠的gaba能传递。最后,我们将探讨gaba能传递的变化是否与雌性小鼠较高的应激易感性有关。在第二个目标中,我们将使用UCLA显微镜监测自由运动小鼠的PV和SOM神经元活动。这些神经元活动的变化将在长期的社会失败压力之前、期间和之后被检测,这些小鼠要么易受这种压力源的影响,要么有弹性。我们还将使用化学发生技术来研究调节PV或SOM神经元活动对应激敏感性的影响。这个研究项目将促进我们对应激易感性是如何被海马gaba能神经元调节的理解。我们的发现还将揭示这些gaba能中间神经元如何参与重复的厌恶经历的处理,这是慢性应激对记忆影响的一种机制。
项目成果
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Wong, TakPan其他文献
Wong, TakPan的其他文献
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{{ truncateString('Wong, TakPan', 18)}}的其他基金
Role of GABAergic inhibition in the hippocampal contribution to stress susceptibility
GABA 能抑制在海马应激易感性贡献中的作用
- 批准号:
RGPIN-2021-03739 - 财政年份:2021
- 资助金额:
$ 2.91万 - 项目类别:
Discovery Grants Program - Individual
Stress and hippocampal volume in rodents, a longitudinal study
啮齿动物的压力和海马体积,一项纵向研究
- 批准号:
RGPIN-2015-04844 - 财政年份:2019
- 资助金额:
$ 2.91万 - 项目类别:
Discovery Grants Program - Individual
Stress and hippocampal volume in rodents, a longitudinal study
啮齿动物的压力和海马体积,一项纵向研究
- 批准号:
RGPIN-2015-04844 - 财政年份:2018
- 资助金额:
$ 2.91万 - 项目类别:
Discovery Grants Program - Individual
Stress and hippocampal volume in rodents, a longitudinal study
啮齿动物的压力和海马体积,一项纵向研究
- 批准号:
RGPIN-2015-04844 - 财政年份:2017
- 资助金额:
$ 2.91万 - 项目类别:
Discovery Grants Program - Individual
Stress and hippocampal volume in rodents, a longitudinal study
啮齿动物的压力和海马体积,一项纵向研究
- 批准号:
RGPIN-2015-04844 - 财政年份:2016
- 资助金额:
$ 2.91万 - 项目类别:
Discovery Grants Program - Individual
Stress and hippocampal volume in rodents, a longitudinal study
啮齿动物的压力和海马体积,一项纵向研究
- 批准号:
RGPIN-2015-04844 - 财政年份:2015
- 资助金额:
$ 2.91万 - 项目类别:
Discovery Grants Program - Individual
Presynaptic contributions in synaptic plasticity
突触前对突触可塑性的贡献
- 批准号:
341403-2008 - 财政年份:2010
- 资助金额:
$ 2.91万 - 项目类别:
Discovery Grants Program - Individual
Presynaptic contributions in synaptic plasticity
突触前对突触可塑性的贡献
- 批准号:
341403-2008 - 财政年份:2009
- 资助金额:
$ 2.91万 - 项目类别:
Discovery Grants Program - Individual
Presynaptic contributions in synaptic plasticity
突触前对突触可塑性的贡献
- 批准号:
341403-2008 - 财政年份:2008
- 资助金额:
$ 2.91万 - 项目类别:
Discovery Grants Program - Individual
Rapid recruitment of GABA A receptors to postsynaptic domains by activation of the P13-Kinase
通过激活 P13 激酶将 GABA A 受体快速募集至突触后结构域
- 批准号:
230458-2000 - 财政年份:2002
- 资助金额:
$ 2.91万 - 项目类别:
Postdoctoral Fellowships
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