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

Theta节律是海马最突出的群体活动，发生在动物探索环境和快速眼动睡眠期间。这种记录在细胞外的节律发生在3-12赫兹之间，对记忆形成至关重要，因为消除它会严重损害记忆。因为这种类型的活动在生理学上是如此重要，了解这种活动的细胞基础已经成为神经科学50多年来的主要课题。广泛接受的模型表明，海马的θ波产生完全依赖于位于大脑腹侧区域的节律神经元，称为内侧隔。让这个领域的每个人都感到惊讶的是，我们最近表明，海马体CA1区产生的θ波是位于海马体内部的神经网络的产物，而不是在内侧隔膜中。在本研究中，我们将进一步研究海马theta节律的特性和潜在机制。更准确地说，我们将研究位于CA3区腹极和背极的两个θ振子的性质。这一点很重要，因为人们一直怀疑海马体的腹侧极和背侧极具有不同的认知作用，例如背极在记忆处理中起关键作用，而腹侧极在情绪处理中至关重要。海马体功能分离为记忆极和情感极的部分原因可能是这些极连接的不同大脑区域。事实上，背极与内侧隔和乳核紧密相连，而腹侧半部分则与前额皮质、杏仁核和伏隔核有独特的联系。然而，海马体是如何同时处理这些不同信息的，目前还不清楚。我们假设海马的背侧和腹侧部分包含可分离的神经元网络。除了研究每个生成器背后的不同细胞机制外，我们还将研究它们如何相互同步。我们提出这些背侧和腹侧振荡器可以耦合取决于可塑性水平。我们将研究参与这种偶联和解偶联过程的受体和信号。总之，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不同的。

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.