Spatial Firing Properties of Hippocampal Neurons

海马神经元的空间放电特性

• 批准号: 7432516
• 负责人: ROBERT L MULLER
• 金额: $ 34.13万
• 依托单位: SUNY DOWNSTATE MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7432516
• 关键词: Accounting; Affect; Agreement; Alzheimer' s Disease; Area; Behavior; Boxing; Brain; Cells; Cholinergic Agents; Cognitive; Collaborations; Computer information processing; Conflict (Psychology); Cues; Data; Dialysis procedure; Drops; Environment; Event; Excision; Fire - disasters; Food; Fostering; Goals; Gold; Hippocampal Formation; Hippocampus (Brain); Human; Illinois; Immunoglobulin G; Individual; Injection of therapeutic agent; Intention; Lesion; Lidocaine; Light; Location; Maps; Medial; Memory; Modeling; Modification; Muscarinics; Neurons; Operative Surgical Procedures; Pattern; Performance; Phase; Physical Dialysis; Picrotoxin; Process; Property; Pyramidal Cells; Range; Rattus; Research Design; Rotation; Scopolamine; Sensory; Shock; Spatial Behavior; Specificity; Stimulus; Stretching; Structure; Systems Theory; Task Performances; Technology; Testing; Time; Visual; Walking; Work; cell type; cholinergic; environmental change; improved; interest; network models; neuromechanism; novel; preference; research study; theories; transmission process; visual stimulus

DESCRIPTION (provided by applicant): The neural mechanisms responsible for sophisticated navigational behavior in rats are currently under intense study for at least two key reasons. First, these mechanisms provide an excellent model for the cognitive processes subserved by the human hippocampus. Second, the location-specific discharge of hippocampal "place cells" (pyramidal cells of CA3 and CA1) and of related cell types in nearby brains areas suggests the existence of a map-like representation of the environment whose activity is essential for solving difficult spatial problems. To better understand the relationship between behavior and coordinated neuronal discharge in the hippocampal formation, we will record from single cells as rats perform simple tasks. In one study, we will compare changes of cell activity in different areas after environmental changes too subtle to cause, "remapping" a major change seen when rats are put into a very different, novel environment. As part of the same study, we will investigate a form of pattern completion in CA1 by looking at how discharge in input areas is affected by removing a cue of known salience. We will also ask how accurately changes in goal location choice caused by putting cues into conflict can be predicted from the way the same conflict causes displacements of place cell firing fields. A third experiment arises from an interesting pharmacologic effect that two well-regarded theories make contrary predictions for concerning navigational performance. Thus, dialyzing the GABAA antagonistic picrotoxin into the medial septum increases the precision of place cell firing while greatly reducing the magnitude of hippocampal theta activity. We will therefore ask if precision of goal location choice in a hidden goal task is unchanged or improved, as expected from crisper place cell firing or disrupted as expected from decrements of theta amplitude. Finally, we will continue to record event-specific activity of hippocampal pyramidal cells to test further the idea that these two forms of processing have extremely similar properties despite the strong difference in the kind of information being processed. We hope the proposed work will shed light on the normal operation of a brain structure whose activity is compromised in pathological states including Alzheimer's disease (AD). We also hope that the use of subtle stimulus transformations to cause simpler, more interpretable changes in single cell activity will be a useful new way of analyzing hippocampal function.

描述(由申请人提供)：负责大鼠复杂导航行为的神经机制目前正处于紧张的研究中，原因至少有两个。首先，这些机制为人类海马体辅助的认知过程提供了一个很好的模型。其次，海马区“地方细胞”(CA3和CA1的锥体细胞)和附近脑区相关细胞类型的位置特异性放电表明，环境的地图状表征的存在，其活动对于解决困难的空间问题至关重要。为了更好地了解行为和海马结构中协调的神经元放电之间的关系，我们将记录大鼠执行简单任务时的单细胞。在一项研究中，我们将比较环境变化后不同区域细胞活动的变化，这些变化太过细微而无法引起，这是当老鼠被置于非常不同的、新的环境中时所看到的重大变化。作为同一研究的一部分，我们将通过观察输入区域的放电如何通过移除已知显著的线索来研究CA1中的一种模式完成形式。我们还将询问，如何从相同的冲突导致位置单元激射场的移动的方式来准确地预测由于将线索放入冲突而导致的目标位置选择的变化。第三个实验来自一种有趣的药理效应，两个著名的理论对导航性能做出了相反的预测。因此，将GABAA拮抗性印防己毒素透析到内侧隔区可以提高定位细胞放电的精确度，同时大大降低海马theta活动的幅度。因此，我们会问在隐藏的目标任务中，目标位置选择的精确度是不是像预期的那样因更清晰的位置单元激发而改变或提高，或者是否如预期的那样因theta幅度的减小而中断。最后，我们将继续记录海马体锥体细胞的事件特异性活动，以进一步测试这两种形式的处理具有极其相似的性质的想法，尽管正在处理的信息种类有很大差异。我们希望这项拟议的工作将有助于揭示大脑结构的正常运作，该结构的活动在包括阿尔茨海默病(AD)在内的病理状态下受到损害。我们还希望，使用微妙的刺激转换来引起单细胞活动的更简单、更可解释的变化将是分析海马体功能的有用的新方法。