Spatial Firing Properties of Hippocampal Neurons

描述（由申请人提供）：由于至少两个关键原因，负责大鼠复杂导航行为的神经机制目前正在进行激烈的研究。首先，这些机制为人类海马体所服务的认知过程提供了一个极好的模型。其次，海马“位置细胞”（CA3和CA1的锥体细胞）和邻近大脑区域的相关细胞类型的位置特异性放电表明，存在一种类似地图的环境表征，其活动对于解决困难的空间问题至关重要。为了更好地理解海马形成中行为和协调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太细微而无法引起的不同区域细胞活动的变化，“重新绘制”当老鼠被置于一个非常不同的新环境中时所看到的主要变化。作为同一研究的一部分，我们将通过观察去除已知显著性线索如何影响输入区域的放电，来研究CA1中模式完成的一种形式。我们还将问，通过同样的冲突导致位置细胞放电场位移的方式，如何准确地预测由冲突提示引起的目标位置选择的变化。第三个实验源于一种有趣的药理学效应，两种公认的理论对导航性能做出了相反的预测。因此，将GABAA拮抗剂微毒素注入内侧隔膜可提高位置细胞放电的精度，同时大大降低海马theta活动的强度。因此，我们将问，在隐藏目标任务中，目标位置选择的精度是否不变或提高，正如预期的那样，从更清晰的位置细胞激活中得到的，或者像预期的那样，从θ振幅的减少中得到破坏。最后，我们将继续记录海马体锥体细胞的事件特异性活动，以进一步验证这两种处理形式具有极其相似的特性，尽管所处理的信息类型存在很大差异。我们希望提出的工作将阐明在包括阿尔茨海默病（AD）在内的病理状态下活动受损的大脑结构的正常运作。我们还希望，利用细微的刺激转化，在单细胞活动中引起更简单、更可解释的变化，将成为分析海马功能的一种有用的新方法。

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.