Modulation of Exocytosis and Excitability in Mature Auditory Brainstem Neurons

成熟听觉脑干神经元胞吐作用和兴奋性的调节

基本信息

项目摘要

PROJECT SUMMARY The major goal of this Administrative Supplement is to determine the changes in neuronal excitability and synaptic strength within the mammalian auditory brainstem during Alzheimer’s disease (AD) and during age related hearing loss (ARHL). We will use well established transgenic mouse lines and strains as experimental models for AD and ARHL. As proposed in our parent R01 grant, we will study two specialized synapses in the auditory brainstem: the large calyx of Held synapse in the medial nucleus of the trapezoid body (MNTB) and the small bouton-type glycinergic and glutamatergic synapses of the lateral superior olive (LSO). These synapses are pivotal for the auditory brainstem circuits that compute high frequency sound source localization. Binaural hearing constitutes an important mechanism for localizing sound sources in mammalian species. It also provides a critical means for filtering important auditory inputs from background noise. The inability to distinguish sound source location or perceive speech in noisy environments are common forms of hearing loss, especially in elderly individuals. Impaired hearing also contributes for social isolation of individulas who suffer from ARHL, which reduces their cognitive stimulation, aggravating or even leading to instances of dementia. The long-term goal is to determine the neuronal excitability and biophysical properties of the MNTB and LSO synapses as animals experience different stages of AD and ARHL progression. We will perform single cell patch clamp electrophysiology recordings in mouse brainstem slices from adult and aging mice at different stages of adulthood and aging in both control and AD models. Our preliminary data show that several fundamental aspects of brainstem synapses and neuronal excitability are significantly changed already in young adult mice (three month old) before severe symptoms of AD become clearly manifest. During adulthood and aging, further synaptic and excitability changes are observed, sometimes in the opposite direction. We thus propose to study the synaptic strength, short-term synaptic plasticity and neuronal excitability of neurons from the brains of AD and ARHL mouse models. The first hypothesis is that the intrinsic excitability of LSO and MNTB neurons is significantly reduced in AD and aging mice models making it harder for excitatory postsynaptic potentials (EPSPs) to reach spike threshold. The second hypothesis is that the synaptic strength in AD and aging brainstem synapses changes significantly because of changes in synaptic vesicle release probability and/or changes in the readily releasable pool size of synaptic vesicles. The results will provide novel insights that reveal several underlying mechanisms responsible for AD pathology and hearing deficits in young adults and aging auditory neurons and synapses. The proposed studies will thus greatly stimulate additional activity leading to significant progress on the fundamental causes of AD dementia and hearing loss in the mammalian brain.
项目总结

项目成果

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HENRIQUE Prado VON GERSDORFF其他文献

HENRIQUE Prado VON GERSDORFF的其他文献

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{{ truncateString('HENRIQUE Prado VON GERSDORFF', 18)}}的其他基金

Modulation of Exocytosis and Excitability in Mature Auditory Brainstem Neurons
成熟听觉脑干神经元胞吐作用和兴奋性的调节
  • 批准号:
    10672937
  • 财政年份:
    2012
  • 资助金额:
    $ 37.59万
  • 项目类别:
Modulation of Exocytosis and Excitability in Mature Auditory Brainstem Neurons
成熟听觉脑干神经元胞吐作用和兴奋性的调节
  • 批准号:
    8968241
  • 财政年份:
    2012
  • 资助金额:
    $ 37.59万
  • 项目类别:
Modulation of Exocytosis and Excitability in Mature Auditory Brainstem Neurons
成熟听觉脑干神经元胞吐作用和兴奋性的调节
  • 批准号:
    10471772
  • 财政年份:
    2012
  • 资助金额:
    $ 37.59万
  • 项目类别:
Modulation of Exocytosis and Excitability in Mature Auditory Brainstem Neurons
成熟听觉脑干神经元胞吐作用和兴奋性的调节
  • 批准号:
    8575315
  • 财政年份:
    2012
  • 资助金额:
    $ 37.59万
  • 项目类别:
Modulation of Exocytosis and Excitability in Mature Auditory Brainstem Neurons
成熟听觉脑干神经元胞吐作用和兴奋性的调节
  • 批准号:
    8432349
  • 财政年份:
    2012
  • 资助金额:
    $ 37.59万
  • 项目类别:
Modulation of Exocytosis and Excitability in Mature Auditory Brainstem Neurons
成熟听觉脑干神经元胞吐作用和兴奋性的调节
  • 批准号:
    9974250
  • 财政年份:
    2012
  • 资助金额:
    $ 37.59万
  • 项目类别:
Dynamic modulation of retinal ribbon-type synapses
视网膜带状突触的动态调制
  • 批准号:
    7383768
  • 财政年份:
    2002
  • 资助金额:
    $ 37.59万
  • 项目类别:
Dynamic Modulation of Retinal Ribbon-Type Synapses
视网膜带状突触的动态调制
  • 批准号:
    7057232
  • 财政年份:
    2002
  • 资助金额:
    $ 37.59万
  • 项目类别:
Dynamic modulation of retinal ribbon-type synapses
视网膜带状突触的动态调制
  • 批准号:
    8632259
  • 财政年份:
    2002
  • 资助金额:
    $ 37.59万
  • 项目类别:
Dynamic Modulation of Retinal Ribbon-Type Synapses
视网膜带状突触的动态调制
  • 批准号:
    6751897
  • 财政年份:
    2002
  • 资助金额:
    $ 37.59万
  • 项目类别:

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