An in vitro model of saccadic eye movement choice

眼跳眼动选择的体外模型

基本信息

  • 批准号:
    8293271
  • 负责人:
  • 金额:
    $ 36.29万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2010
  • 资助国家:
    美国
  • 起止时间:
    2010-08-01 至 2014-06-30
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): The overall goal of this research plan is to understand the role of the basal ganglia (BG) and superior colliculus (SC) in saccadic eye movement choice and decision-making. This application focuses on developing an in vitro brain slice model with which we will extend our recent in vivo results and investigate the biophysics of a circuit involved in choice and decision-making. This proposal aims to link the properties of neurons and their circuits to behavior in order to elucidate the role of the SC and the BG in eye-movement related cognitive processes. We have four specific aims; 1) Map response patterns across the SC. Voltage imaging will be used to map the spatial patterns of signal spread following electrical stimulation in the superficial SC (sSC) and intermediate SC (iSC). This aim will provide a basic assessment of the spatial extent of both intra- and inter-laminar circuitry within the SC; 2) Evaluate inhibition and excitation in SC activity patterns. In this aim we will test for the existence of three specific interlaminar pathways: an excitatory pathway arising from the sSC extending to the iSC, an inhibitory pathway arising from the iSC and extending into the sSC and an excitatory pathway arising from the iSC and extending into the sSC. We will use voltage imaging in conjunction with patch clamping to study responses to sSC and iSC stimulation, and resolve these responses into contributions mediated by glutamatergic and GABAergic synapses. Experiments with synaptic receptor antagonists will assess the role of glutamatergic and GABAergic transmission in both intra- and interlaminar circuits; 3) Determine the influence of BG output on the response pattern across the SC. The experiments of this aim will test the hypothesis that translation of visual information from sSC into motor information in iSC is modulated by inhibition from the substantia nigra pars reticulata of the BG. We will apply electrical stimulation in the nigra to determine how the nigra modulates SC responses to sSC and iSC stimulation; 4) Map response patterns across the SC in monkey SC. We will develop an in vitro preparation of the SC using monkey tissue. Experiments as outlined in aims 1 and 2 will be performed. We will test the hypothesis that the underlying circuits in monkey and rodent SC are homologous. Because the BG and its target structures are implicated in many neurological and psychiatric disease states, the results of our experiments should lead to important insights into the functioning of these circuits and the biophysical mechanisms underlying complex behavioral and cognitive processing in both health and disease. PUBLIC HEALTH RELEVANCE: A sine qua non of higher mental function is our ability to make decisions. Extreme fluctuations in choice behavior may underlie certain neurological and psychiatric diseases such as schizophrenia, attention deficit disorder, Tourette Syndrome and obsessive compulsive disorder. Eye movement abnormalities are also associated with these cortico-basal ganglia diseases. Therefore, a deeper understanding of the basal ganglia - superior colliculus pathway and circuitry and ultimately their role in higher mental function, may lead to better diagnostics, better ways to assess therapies and should provide important insights into the mechanisms of symptomology in these disease states.
描述(由申请人提供):本研究计划的总体目标是了解基底神经节(BG)和上级丘(SC)在扫视眼球运动选择和决策中的作用。本申请的重点是开发一种体外脑切片模型,我们将扩展我们最近的体内结果,并研究参与选择和决策的电路的生物物理学。本研究旨在将神经元及其回路的特性与行为联系起来,以阐明SC和BG在眼动相关认知过程中的作用。我们有四个具体目标; 1)绘制SC上的响应模式。电压成像将用于绘制浅表SC(sSC)和中间SC(iSC)中电刺激后信号传播的空间模式。该目的将提供SC内层内和层间回路的空间范围的基本评估; 2)评价SC活动模式中的抑制和兴奋。在这一目标中,我们将测试三个特定的层间通路的存在:从sSC延伸到iSC的兴奋性通路,从iSC产生并延伸到sSC的抑制性通路和从iSC产生并延伸到sSC的兴奋性通路。我们将使用电压成像结合膜片钳来研究对sSC和iSC刺激的反应,并将这些反应分解为由谷氨酸能和GABA能突触介导的贡献。用突触受体拮抗剂的实验将评估谷氨酸能和GABA能传递在层内和层间回路中的作用; 3)确定BG输出对整个SC的反应模式的影响。该目的的实验将检验以下假设:从sSC到iSC中的运动信息的视觉信息的翻译是由BG的黑质网状部的抑制调节的。我们将在黑质中施加电刺激以确定黑质如何调节SC对sSC和iSC刺激的反应; 4)绘制猴SC中SC的反应模式。我们将使用猴组织开发SC的体外制备。将进行目标1和2中概述的实验。我们将检验猴子和啮齿动物SC中的潜在回路是同源的这一假设。由于BG及其靶结构与许多神经和精神疾病状态有关,因此我们的实验结果应有助于深入了解这些回路的功能以及健康和疾病中复杂行为和认知过程的生物物理机制。 公共卫生相关性:高级心理功能的必要条件是我们做出决定的能力。选择行为的极端波动可能是某些神经和精神疾病的基础,如精神分裂症、注意力缺陷障碍、图雷特综合症和强迫症。眼球运动异常也与这些皮质基底神经节疾病有关。因此,更深入地了解基底神经节-上级丘通路和电路,并最终在更高的精神功能中的作用,可能会导致更好的诊断,更好的方法来评估治疗,并应提供重要的见解,这些疾病状态的神经病学的机制。

项目成果

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Michele A Basso其他文献

Michele A Basso的其他文献

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{{ truncateString('Michele A Basso', 18)}}的其他基金

Changes across the lifespan in the use of heuristics to guide decision-making
使用启发式方法指导决策的整个生命周期的变化
  • 批准号:
    10542573
  • 财政年份:
    2019
  • 资助金额:
    $ 36.29万
  • 项目类别:
Changes across the lifespan in the use of heuristics to guide decision-making
使用启发式方法指导决策的整个生命周期的变化
  • 批准号:
    10589139
  • 财政年份:
    2019
  • 资助金额:
    $ 36.29万
  • 项目类别:
Changes across the lifespan in the use of heuristics to guide decision-making
使用启发式方法指导决策的整个生命周期的变化
  • 批准号:
    10115564
  • 财政年份:
    2019
  • 资助金额:
    $ 36.29万
  • 项目类别:
Changes across the lifespan in the use of heuristics to guide decision-making
使用启发式方法指导决策的整个生命周期的变化
  • 批准号:
    9922203
  • 财政年份:
    2019
  • 资助金额:
    $ 36.29万
  • 项目类别:
Interrogation of Eye Movement Circuits using fMRI and Optogenetics
使用功能磁共振成像和光遗传学询问眼动回路
  • 批准号:
    8918629
  • 财政年份:
    2014
  • 资助金额:
    $ 36.29万
  • 项目类别:
Interrogation of Eye Movement Circuits using fMRI and Optogenetics
使用功能磁共振成像和光遗传学询问眼动回路
  • 批准号:
    8776030
  • 财政年份:
    2014
  • 资助金额:
    $ 36.29万
  • 项目类别:
2013 Eye Movements: The Motor System that Sees the World GRC & GRS
2013 眼动:看世界的运动系统 GRC
  • 批准号:
    8527325
  • 财政年份:
    2013
  • 资助金额:
    $ 36.29万
  • 项目类别:
A new model of the role of the basal ganglia in eye movement initiation.
基底神经节在眼球运动启动中的作用的新模型。
  • 批准号:
    8776716
  • 财政年份:
    2013
  • 资助金额:
    $ 36.29万
  • 项目类别:
A new model of the role of the basal ganglia in eye movement initiation.
基底神经节在眼球运动启动中的作用的新模型。
  • 批准号:
    8635227
  • 财政年份:
    2013
  • 资助金额:
    $ 36.29万
  • 项目类别:
MOVEMENT DISORDERS AND EYE MOVEMENTS
运动障碍和眼球运动
  • 批准号:
    8358208
  • 财政年份:
    2011
  • 资助金额:
    $ 36.29万
  • 项目类别:

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