Cerebellar Modulation of Frontal Cortical Function

额叶皮质功能的小脑调节

基本信息

  • 批准号:
    8418762
  • 负责人:
  • 金额:
    $ 28.7万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2009
  • 资助国家:
    美国
  • 起止时间:
    2009-03-01 至 2015-02-28
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): The developmental loss of cerebellar Purkinje cells that occurs in autism spectrum disorders has been associated with a heterogeneous pattern of cognitive deficits that cannot be explained by a unitary cognitive impairment. It is very unlikely that the simple loss of cerebellar Purkinje cells can directly account for these myriad cognitive deficits. Rather, it is likely that autism is, at its essence, a disconnection syndrome that results, at least in part, from a disruption of cerebellar modulation of the prefrontal cortex (PFC). We have exciting new data suggesting that the cerebellum modulates PFC dopamine levels. Here we propose to investigate the disconnection hypothesis that cerebellar pathology results in dopaminergic abnormalities in the prefrontal cortex (PFC) and underlies some of the core neuropsychiatric symptomatology of autism. In Aim 1 we will determine the pathway(s) whereby the cerebellum modulates dopamine release in the PFC and glutamate release in subnuclei comprising the cerebellum to PFC pathways and the neurochemical, electrophysiological, anatomical, and behavioral consequences of a disconnection between these two structures. Aim 1 will compare wildtype (control) and Lurcher mice that loose all Purkinje cells, to determine the consequences of complete loss of Purkinje cells on cerebellar-PFC communication. Aim 2 will investigate the behavioral and physiological consequences of partial loss of Purkinje cells - as typically found in autistic brains. Using Lurcher-wildtype chimeras with varying developmental loss in Purkinje cell numbers we will determine how neurochemical, electrophysiological, anatomical and behavioral indicators of PFC function depend on Purkinje cell number. Given the well documented reductions in cerebellar neuron number that are found in autism spectrum disorders, the neurochemical, electrophysiological, anatomical and behavioral analyses of chimeric mice presents a unique opportunity to model both the developmental and cerebellar aspects of these syndromes.
描述(由申请人提供):发生在自闭症谱系障碍中的小脑浦肯野细胞的发育丧失与不能用单一认知障碍解释的认知缺陷的异质模式相关。小脑浦肯野细胞的简单缺失不太可能直接解释这些无数的认知缺陷。更确切地说,自闭症的本质可能是一种分离综合征,至少部分是由于前额叶皮质(PFC)的小脑调节功能被破坏而导致的。我们有令人兴奋的新数据表明小脑调节PFC多巴胺水平。在这里,我们建议调查的断开假说,小脑的病理结果在前额叶皮层(PFC)的多巴胺能异常,并根据一些核心的神经精神病学自闭症。在目标1中,我们将确定小脑调节PFC中多巴胺释放和亚核中谷氨酸释放的途径,包括小脑到PFC途径,以及这两个结构之间断开的神经化学,电生理,解剖和行为后果。目的1将比较野生型(对照)和失去所有浦肯野细胞的Lurcher小鼠,以确定浦肯野细胞完全丧失对小脑PFC通讯的影响。目标2将研究浦肯野细胞部分丧失的行为和生理后果--这在自闭症患者的大脑中是典型的。使用Lurcher野生型嵌合体与不同的发展损失浦肯野细胞的数量,我们将确定如何神经化学,电生理,解剖和行为指标PFC功能依赖于浦肯野细胞的数量。鉴于在自闭症谱系障碍中发现的小脑神经元数量的减少有据可查,嵌合小鼠的神经化学、电生理、解剖和行为分析提供了一个独特的机会来模拟这些综合征的发育和小脑方面。

项目成果

期刊论文数量(10)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Reorganization of circuits underlying cerebellar modulation of prefrontal cortical dopamine in mouse models of autism spectrum disorder.
  • DOI:
    10.1007/s12311-013-0462-2
  • 发表时间:
    2013-08
  • 期刊:
  • 影响因子:
    3.5
  • 作者:
    Rogers, Tiffany D.;Dickson, Price E.;McKimm, Eric;Heck, Detlef H.;Goldowitz, Dan;Blaha, Charles D.;Mittleman, Guy
  • 通讯作者:
    Mittleman, Guy
Behavioral flexibility in a mouse model of developmental cerebellar Purkinje cell loss.
  • DOI:
    10.1016/j.nlm.2010.05.010
  • 发表时间:
    2010-09
  • 期刊:
  • 影响因子:
    2.7
  • 作者:
    Dickson, Price E.;Rogers, Tiffany D.;Del Mar, Nobel;Martin, Loren A.;Heck, Detlef;Blaha, Charles D.;Goldowitz, Daniel;Mittleman, Guy
  • 通讯作者:
    Mittleman, Guy
Repetitive behavior and increased activity in mice with Purkinje cell loss: a model for understanding the role of cerebellar pathology in autism.
  • DOI:
    10.1111/j.1460-9568.2009.07073.x
  • 发表时间:
    2010-02
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Martin LA;Goldowitz D;Mittleman G
  • 通讯作者:
    Mittleman G
Impaired hypercarbic and hypoxic responses from developmental loss of cerebellar Purkinje neurons: implications for sudden infant death syndrome.
  • DOI:
    10.1007/s12311-014-0592-1
  • 发表时间:
    2014-12
  • 期刊:
  • 影响因子:
    3.5
  • 作者:
    Calton, M.;Dickson, P.;Harper, R. M.;Goldowitz, D.;Mittleman, G.
  • 通讯作者:
    Mittleman, G.
Cerebellar Purkinje Cells Generate Highly Correlated Spontaneous Slow-Rate Fluctuations.
小脑浦肯野细胞产生高度相关的自发慢速波动。
  • DOI:
    10.3389/fncir.2017.00067
  • 发表时间:
    2017
  • 期刊:
  • 影响因子:
    3.5
  • 作者:
    Cao Y;Liu Y;Jaeger D;Heck DH
  • 通讯作者:
    Heck DH
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Charles Blaha其他文献

Charles Blaha的其他文献

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{{ truncateString('Charles Blaha', 18)}}的其他基金

A high oxygen capacity cell scaffold for the intravascular bioartifical pancreas (iBAP)
用于血管内生物人工胰腺(iBAP)的高氧容量细胞支架
  • 批准号:
    9899079
  • 财政年份:
    2019
  • 资助金额:
    $ 28.7万
  • 项目类别:
A silicon nanopore membrane blood filter enabling anticoagulant free continuous renal replacement therapy for acute kidney injury
硅纳米孔膜血液过滤器可实现无抗凝剂的连续肾脏替代治疗急性肾损伤
  • 批准号:
    10546997
  • 财政年份:
    2019
  • 资助金额:
    $ 28.7万
  • 项目类别:
Development of advanced voltammetric method for basal neurotransmitter level measurement
开发用于基础神经递质水平测量的先进伏安法
  • 批准号:
    9796267
  • 财政年份:
    2019
  • 资助金额:
    $ 28.7万
  • 项目类别:
In Vivo Fluorescent Microscopy Analysis of Motor Cortex Activation by STN DBS
STN DBS 对运动皮层激活的体内荧光显微镜分析
  • 批准号:
    10023233
  • 财政年份:
    2018
  • 资助金额:
    $ 28.7万
  • 项目类别:
An Intravascular Bioartificial Pancreas (iBAP)
血管内生物人工胰腺 (iBAP)
  • 批准号:
    8823183
  • 财政年份:
    2014
  • 资助金额:
    $ 28.7万
  • 项目类别:
An implantable hemodialyzer for treatment of End-Stage Renal Disease
用于治疗终末期肾病的植入式血液透析器
  • 批准号:
    8714973
  • 财政年份:
    2014
  • 资助金额:
    $ 28.7万
  • 项目类别:
Cerebellar Modulation of Frontal Cortical Function
额叶皮质功能的小脑调节
  • 批准号:
    7656128
  • 财政年份:
    2009
  • 资助金额:
    $ 28.7万
  • 项目类别:
Cerebellar Modulation of Frontal Cortical Function
额叶皮质功能的小脑调节
  • 批准号:
    8033156
  • 财政年份:
    2009
  • 资助金额:
    $ 28.7万
  • 项目类别:
Cerebellar Modulation of Frontal Cortical Function
额叶皮质功能的小脑调节
  • 批准号:
    8239877
  • 财政年份:
    2009
  • 资助金额:
    $ 28.7万
  • 项目类别:

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