The role of cholinergic modulation in hippocampal information processing

描述(申请人提供)：使用经验指导行为(学习)的能力是大脑最显著的能力之一。我们的目标是了解活动如何 神经回路的可塑性既是学习的基础，也是使用所学信息的能力的基础 来做决定。我们研究了随着动物行为的改变，海马体中的信息处理是如何变化的。我们发现，随着动物运动得更快，海马输出区CA1从大CA3到大EC驱动的平稳过渡。作为力矩速度函数的变化是迅速的，在新的环境中最明显。CA1中协同刺激性活动的水平反映了这种转变：细胞对 在低速时高度相关，随着动物移动得更快，相关性逐渐降低。这些结果表明，行为在代表存储的联系的相关活动和海马体中更独立的感觉表征之间驱动着动态平衡。这种动态平衡非常适合支持海马体回路的助记功能，包括在探索新的地方时形成可靠的记忆。这笔拨款的目的是研究推动这种动态平衡的机制。目前已有的结果表明，内侧隔核和Broca腹侧斜角带(MS/DB)的胆碱能调制是调节海马回路的中枢，因此我们将在清醒的行为动物中使用多电极记录和有针对性的光遗传操作来确定海马胆碱能输入在调节海马信息处理中的时刻变化中的作用。我们的具体目标是：1)测试MS/DB输入群体的调节足以控制海马区信息处理的动态平衡的假设，以及2)测试动态水平的MS/DB胆碱能神经元活动对快速学习重要的假设。为实现这些目标而进行的实验有可能为海马体电路的许多功能的调节提供一个基本的新理解。

DESCRIPTION (provided by applicant): The ability to use experience to guide behavior (to learn) is one of the most remarkable abilities of the brain. Our goal is to understand how activity and plasticity in neural circuits underlie both learning and the ability to use learned information to make decisions. We have examined how information processing in the hippocampus changes as animals behavior changes. We found that that there is a smooth transition from greater CA3 to greater EC drive of hippocampal output area CA1 as animals move more quickly. Changes as function of moment speed are rapid and are most pronounced in new environments. The level of coordinated spiking activity in CA1 reflects that transition: cell pairs are highly correlated at low speeds and become progressively less correlated as animals move more quickly. These results suggest that behavior drives a dynamic balance between correlated activity representing stored associations and more independent sensory representations in the hippocampus. This dynamic balance is well suited to support the mnemonic functions of the hippocampal circuit, including the formation of reliable memories during exploration of new places. The goal of this grant is to investigate the mechanism that drives this dynamic balance. Currently available results suggest that cholinergic modulation from the medial septum and the ventral diagonal band of Broca (MS/DB) is central to regulating hippocampal circuits, so we will use multielectrode recording and targeted optogenetic manipulations in awake, behaving animals to determine the role of cholinergic inputs to the hippocampus in regulating moment-by-moment changes in hippocampal information processing. Our Specific Aims are: 1) Test the hypothesis that modulation of MS/DB input populations is sufficient to control the dynamic balance of information processing in the hippocampus and 2) Test the hypothesis that dynamic levels of MS/DB cholinergic neuron activity are important for rapid learning. The experiments carried out to accomplish these aims have the potential to provide a fundamental new understanding of the regulation of the many functions of the hippocampal circuit.