Medial septum in spatial memory and theta rhythm

描述(申请人提供)：学习和记忆障碍是老年人的常见症状，在阿尔茨海默病患者中非常严重。显示年龄相关性变性的大脑区域是Broca复合体(MSDB)的内侧隔-斜角带，而MSDB的持续退化发生在阿尔茨海默病中。MSDB为海马体提供主要的皮质下输入，海马体是众所周知的大脑结构，对记忆至关重要。到目前为止，大多数研究都集中在胆碱能MSDB神经元上，因为已经有了选择性损伤这些神经元的药物。对非胆碱能MSDB神经元的功能知之甚少，尽管它们向海马区的投射可能与胆碱能神经元一样大。建议的研究假设非胆碱能MSDB神经元对空间记忆很重要，因为它们调节海马区的生理。MSDB内注射红藻氨酸可损伤非胆碱能MSDB神经元，保护胆碱能神经元。本建议中的研究内容如下：1)提供有关海人酸对非胆碱能MSDB神经元的损伤作用的更多信息，2)检测间隔内给予海人酸对空间记忆的影响，3)研究间隔内给予海人酸引起的空间记忆变化是否源于海马区细胞的改变，4)确定间隔内给予红藻氨酸对海马区和内嗅皮层节律性活动模式(theta节律)的影响。建议的研究集中在以前没有得到太多研究的神经元群体，因此，这一建议的结果将极大地促进我们对非胆碱能MSDB神经元在记忆中的作用的了解。此外，还将了解内侧隔-斜角带复合体和海马体之间的相互作用。由于这些大脑区域在记忆中非常重要，这一提议的结果将对治疗和预防记忆损伤具有重要的广泛意义。

DESCRIPTION (provided by applicant): Learning and memory impairments are a common complaint in the elderly and are very severe in patients with Alzheimer's disease. A brain area that shows age-related degeneration is the medial septum-diagonal band of Broca complex (MSDB), and consistent degeneration of the MSDB occurs in Alzheimer's disease. The MSDB provides a major subcortical input to the hippocampus, a brain structure well known to be critical for memory. To date, most studies have focused on cholinergic MSDB neurons because agents have been available to damage these neurons selectively. Less is known about the function of noncholinergic MSDB neurons, even though their projection to the hippocampus can be as large as the cholinergic neurons. The proposed studies hypothesize that noncholinergic MSDB neurons are important for spatial memory because they modulate hippocampal physiology. Administration of kainic acid into the MSDB can damage noncholinergic MSDB neurons and spare the cholinergic neurons. The studies in this proposal do the following: 1) provide more information regarding the damaging effects of kainic acid administration on noncholinergic MSDB neurons, 2) examine the effects of intraseptal kainic acid administration on spatial memory, 3) investigate whether changes in spatial memory caused by intraseptal kainic acid is due to alterations of hippocampal place cells, 4) determine the effects of intraseptal kainic acid administration on rhythmic activity patterns (theta rhythm) in the hippocampus and entorhinal cortex. The proposed studies focus on a population of neurons that has not received much previous study, and therefore, the results of this proposal will greatly advance our knowledge of the role of noncholinergic MSDB neurons in memory. Additionally, much will be learned of the interaction between the medial septum-diagonal band complex and the hippocampus. Because these brain areas are so important in memory, the results from this proposal will have important broad implications in the treatment and prevention of memory impairments.