Cellular and Network dynamics of medial temporal lobe memory structures

新皮层（nCTX）和海马体（HPC）之间的解剖连接，以内侧颞叶（MTL）为中心，被认为是大脑形成和储存某些形式记忆的硬件。这些神经回路中神经活动的破坏会导致顺行性和逆行性失忆症状。因此，要了解记忆的形成和存储方式，就需要了解该电路的正常活动模式。在记忆任务的执行和保持过程中，MTL神经元表现出明显的振荡同步，其频率参数取决于行为状态。这些不同的状态依赖性活动模式是由于内源性神经调节剂水平的波动。MTL中这些不同的振荡状态的含义是，不同的模式可能使这种电路倾向于不同的信息处理目的。事实上，某些模式，如theta/gamma节律，已被证明可以优化该电路中可塑性的表达。本研究的目的是在细胞和电路水平上检查MTL内结构的电生理特性和状态依赖性神经调节，重点是内嗅皮层。EC是MTL的一个节点元素，因为它形成了nCTX和HPC之间的双向接口。欧共体内的细胞受状态依赖的神经调节影响，影响其内在特性、网络相互作用，从而影响信息处理。虽然我们对EC主神经元的内在特性的认识相当复杂，但我们对EC网络及其动力学的理解仍然有限。本研究的目的是研究EC细胞之间的突触相互作用以及胆碱能和5 -羟色胺能神经调节对它们的影响。通过这些方法获得的结果将深入了解MTL内的动态处理特征，并可能为涉及记忆形成和/或存储的大脑机制提供线索。

The anatomical connections between the neocortex (nCTX) and the hippocampus (HPC), centered in the medial temporal lobe (MTL), are thought to be the brain's hardware for the formation and storage of certain forms of memory.  The disruption of neural activity in these circuits causes both anterograde and retrograde amnesic symptoms. Therefore, an understanding of how memory formation and storage takes place requires an understanding of the normal activity patterns of this circuitry. During the performance and retention of memory tasks MTL neurons display prominent oscillatory synchronization whose frequency parameters depend upon behavioural state.  These different patterns of state-dependent activity are due to fluctuating levels of endogenous neuromodulators. The implication of these different oscillatory states in the MTL is that different patterns may predispose this circuitry for different information processing purposes.  In fact, certain patterns such as the theta/gamma rhythm have been shown to optimize the expression of plasticity in this circuitry.      The objective of this research is to examine, at the cellular and circuit level, the electrophysiological properties and state-dependent neuromodulation of structures within the MTL, focusing on the entorhinal cortex. The EC is a nodal element of the MTL since it forms a bi-directional interface between the nCTX and HPC. Cells within the EC are subject to state-dependent neuromodulatory influences that affect their intrinsic properties, their network interactions and thus, the processing of information. While our knowledge of the intrinsic properties of EC principal neurons is quite sophisticated, our understanding of the EC network and its dynamics is still limited. The aim of this proposal is to study the synaptic interactions between EC cells and the effects of cholinergic and serotonergic neuromodulation upon them.      The results obtained via these methods will yield insights into the dynamic processing characteristics within the MTL and may provide hints as to the brain mechanisms involved in memory formation and/or storage.