Investigating the cellular basis for distinct theta rhythm generators in the dorsal and ventral hippocampus

研究背侧和腹侧海马中不同θ节律发生器的细胞基础

• 批准号: 238770-2011
• 负责人: Williams, Sylvain
• 金额: $ 1.97万
• 依托单位: McGill University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2012
• 资助国家: 加拿大
• 起止时间: 2012-01-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=506438
• 关键词: Investigating; cellular; basis; distinct; theta

Theta rhythm is the most prominent population activity in hippocampus and takes place when the animal is exploring the environment and during REM sleep. This type of rhythm recorded extracellularly occurs at a frequency between 3-12 Hz is known to be essential for memory formation since eliminating it severely impairs memory. Because this type of activity is so important physiologically, understanding the cellular basis of this activity has been a major topic in neuroscience for more than 50 years. The widely accepted model suggests that theta generation in hippocampus is completely dependent on rhythmic neurons located in a ventral brain area named the medial septum. Much to the surprise of everyone in the field, we have shown recently that theta generation in the CA1 area of the hippocampus is a product of neuronal networks located within the hippocampus itself and not in the medial septum. In this proposal, we will further investigate the properties and underlying mechanisms underlying theta rhythm in hippocampus. More precisely, we will investigate the properties of two theta oscillators located in the ventral and dorsal pole of area CA3. This is important since it has been suspected that the ventral and dorsal poles of the hippocampus have much different cognitive roles such that the dorsal pole plays a key role in memory processing whereas the ventral pole is essential for emotional processing. This dissociation of hippocampal function into a memory and emotional pole may be due in part by the distinct brain regions these poles are connected to. Indeed, the dorsal pole is heavily connected to the medial septum and mammilary nuclei whereas the ventral half has unique projections to the prefrontal cortex, amygdala and nucleus accumbens. However, it remains undertermined how the hippocampus can process such different information sumultaneously. We hypothesize that the dorsal and ventral parts of the hippocampus contains dissociable neuronal networks. In addition to investigating the differential cellular mechanisms underlying each generator, we will investigate how they can synchronize with each other. We propose that these dorsal and ventral oscillators can couple depending on the level of plasticity. We will investigate the receptors and the signaling involved in this coupling and uncoupling process. In summary, we propose a physiological substrate to explain how the hippocampus can perform spatial and emotional tasks simultaneously and plan to determine at the cellular level how these dorsal and ventral networks are distinct.

西塔节律是海马体中最显著的群体活动，发生在动物探索环境和快速眼动睡眠期间。这种在细胞外记录的节律发生在3-12赫兹之间的频率上，众所周知，这种节律对记忆的形成是必不可少的，因为消除它会严重损害记忆。由于这种类型的活动在生理上是如此重要，了解这种活动的细胞基础一直是神经科学50多年来的一个主要主题。被广泛接受的模型表明，海马体中theta的产生完全依赖于位于大脑腹侧隔区的节律性神经元。令该领域的每个人都感到惊讶的是，我们最近表明，海马区CA1区的theta生成是位于海马体本身而不是内侧隔区的神经元网络的产物。在这项提案中，我们将进一步研究海马体中theta节奏的特性和潜在机制。更准确地说，我们将研究位于CA3区腹极和背极的两个theta振子的性质。这一点很重要，因为人们一直怀疑，海马体的腹极和背极具有非常不同的认知角色，因此背极在记忆处理中起着关键作用，而腹极对情感处理是必不可少的。海马体功能与记忆和情绪极的分离可能部分是由于这些极与不同的大脑区域相连。事实上，背极与内侧隔核和乳房核紧密相连，而腹侧半极有独特的投射到前额叶皮质、杏仁核和伏隔核。然而，海马体如何同时处理这些不同的信息仍未确定。我们假设，海马体的背侧和腹侧部分包含可分离的神经元网络。除了研究每个发电机背后的差异细胞机制外，我们还将研究它们如何相互同步。我们认为，这些背部和腹部振荡器可以耦合，取决于可塑性的水平。我们将研究参与这一偶联和解偶联过程的受体和信号。综上所述，我们提出了一个生理基础来解释海马体如何同时执行空间和情感任务，并计划在细胞水平上确定这些背侧和腹侧网络是如何区分的。