Cellular and Network dynamics of medial temporal lobe memory structures

以内侧颞叶（MTL）为中心的新皮层（nCTX）和海马（HPC）之间的解剖学连接被认为是大脑形成和存储某些形式记忆的硬件。 这些回路中神经活动的中断会引起顺行性和逆行性遗忘症状。因此，要了解记忆的形成和储存是如何发生的，就需要了解这个回路的正常活动模式。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质水平的波动。MTL中这些不同的振荡状态的含义是，不同的模式可能倾向于这种电路用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回路中可塑性的表达。 本研究的目的是检查，在细胞和电路水平，电生理特性和状态依赖的神经调制的MTL内的结构，专注于内嗅皮层。EC是MTL的节点元件，因为它在nCTX和HPC之间形成双向接口。EC内的细胞受到状态依赖性神经调节的影响，影响其内在特性，网络相互作用，从而影响信息的处理。虽然我们的知识EC主神经元的内在属性是相当复杂的，我们的EC网络及其动力学的理解仍然是有限的。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多巴胺能神经调节对它们的影响。 通过这些方法获得的结果将产生洞察MTL内的动态处理特性，并可能提供线索，涉及记忆形成和/或存储的大脑机制。

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.