Generating mouse models with cell type-specific and reversible GABA deficiency

生成具有细胞类型特异性和可逆性 GABA 缺陷的小鼠模型

基本信息

  • 批准号:
    10679713
  • 负责人:
  • 金额:
    $ 23.73万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2023
  • 资助国家:
    美国
  • 起止时间:
    2023-06-01 至 2025-05-31
  • 项目状态:
    未结题

项目摘要

ABSTRACT GABAergic neurons are the main inhibitory neurons in the adult nervous system. There are diverse cortical and subcortical GABAergic interneurons and projection neurons with different physiological properties, connectivity, and functions. However, few studies have been able to investigate the functions of specific subclasses by perturbing GABA release selectively. We propose an approach to target GABA synthesis in subclasses of GABAergic neurons. GAD activity requires the cofactor pyridoxal-5-phosphate (PLP). PLP deficiency can be achieved by knocking out the rate limiting enzyme in PLP synthesis: pyridoxine-5-phosphate oxidase (PNPO). Moreover, PLP deficiency can be rescued by systemic PLP administration. We therefore propose to generate cell type specific PNPO deficiency mouse models. We will first generate models with GABA deficiency in well-studied but highly distinct cell types to test the feasibility of our approach: 1) the parvalbumin (PV)-positive GABAergic neurons; 2) the VIP-positive GABAergic neurons; 3) the striatal dopamine D1 receptor expressing neurons; and 4) the striatal dopamine D2 receptor expressing neurons. Mice will be assessed for general health, feeding, drinking, sleep, and potential seizures. In addition, working memory, reference memory, reversal learning, motor coordination and motor learning will be examined. Brain morphology and electrophysiology will be assessed. Levels of GABA, other PNPO-dependent neurotransmitters, and their metabolites will be measured. The main goal of this R21 application is to test the feasibility of such an approach. These models are potentially significant research tools for the research community and may have a broad impact given the diverse distribution and functions of different GABAergic projection neurons and interneurons.
摘要

项目成果

期刊论文数量(0)
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Xiaoxi Zhuang其他文献

Xiaoxi Zhuang的其他文献

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{{ truncateString('Xiaoxi Zhuang', 18)}}的其他基金

Postsynaptic mechanisms underlying negative prediction error
负预测误差背后的突触后机制
  • 批准号:
    10682471
  • 财政年份:
    2022
  • 资助金额:
    $ 23.73万
  • 项目类别:
Postsynaptic mechanisms underlying negative prediction error
负预测误差背后的突触后机制
  • 批准号:
    10539883
  • 财政年份:
    2022
  • 资助金额:
    $ 23.73万
  • 项目类别:
Drosophila and mouse models of PNPO deficiency
PNPO 缺乏症的果蝇和小鼠模型
  • 批准号:
    10307547
  • 财政年份:
    2019
  • 资助金额:
    $ 23.73万
  • 项目类别:
Drosophila and mouse models of PNPO deficiency
PNPO 缺乏症的果蝇和小鼠模型
  • 批准号:
    9913752
  • 财政年份:
    2019
  • 资助金额:
    $ 23.73万
  • 项目类别:
Drosophila and mouse models of PNPO deficiency
PNPO 缺乏症的果蝇和小鼠模型
  • 批准号:
    10058294
  • 财政年份:
    2019
  • 资助金额:
    $ 23.73万
  • 项目类别:
Drosophila and mouse models of PNPO deficiency
PNPO 缺乏症的果蝇和小鼠模型
  • 批准号:
    10526424
  • 财政年份:
    2019
  • 资助金额:
    $ 23.73万
  • 项目类别:
RNA methylation in synaptic plasticity and drug-seeking
RNA甲基化在突触可塑性和药物寻找中的作用
  • 批准号:
    10159882
  • 财政年份:
    2017
  • 资助金额:
    $ 23.73万
  • 项目类别:
Genetic dissection of neural pathways for appetitive associative learning
食欲联想学习神经通路的遗传解剖
  • 批准号:
    8976537
  • 财政年份:
    2015
  • 资助金额:
    $ 23.73万
  • 项目类别:
Genetic dissection of neural pathways for appetitive associative learning
食欲联想学习神经通路的遗传解剖
  • 批准号:
    9066127
  • 财政年份:
    2015
  • 资助金额:
    $ 23.73万
  • 项目类别:
Nicotine mitigates dopamine blockade-induced aberrant plasticity and learning
尼古丁减轻多巴胺阻断引起的异常可塑性和学习
  • 批准号:
    8633066
  • 财政年份:
    2013
  • 资助金额:
    $ 23.73万
  • 项目类别:

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