Dendritic Integration in the Entorhinal Cortex

描述（由申请人提供）：记忆的形成和巩固需要海马和新皮层之间通过内嗅皮层（EC）的双向交流。EC层V神经元是海马处理输出的主要目标，并依次投射到皮层区域；因此，这些神经元可能在记忆的形成和巩固中发挥重要作用。此外，它们具有突出的顶端树突，这些树突在EC浅层中以复杂的簇状延伸和分支，已知来自不同皮层区域的轴突在EC第2层和第3层神经元上形成突触。我们的初步数据显示，这些簇状植物带有许多刺。这些棘的存在，再加上它们与来自皮质区域的轴突的接近，表明这些轴突可能在V层神经元的远端树突上形成谷氨酸能突触接触。这项研究的长期目标是通过阐明内嗅层V神经元如何将它们从海马体接收的突触输入与其他输入整合，从而产生输出到新皮层，从而为记忆的处理提供新的见解。双光子Ca2+成像，谷氨酸释放和电生理技术将被用来表征大鼠内嗅皮层V层神经元树突整合的不同方面。该项目将集中在三个具体目标上：(1)验证预测EC层V神经元的远端顶端树突被谷氨酸能输入激活，其特征与海马近端突触不同；(2)验证近端和远端隔室可以通过反向传播动作电位（bAPs）进行通信的预测；(3)验证EC层V神经元远端树突可引发改变内嗅输出的树突尖峰的预测。获得的关于这些神经元树突特定计算能力的信息将揭示正常和病理神经元活动期间的信号处理。我们对信息是如何在大脑的这一关键区域传递和存储的理解的改进，最终可能会指导治疗这一区域特别脆弱的疾病的治疗策略，如阿尔茨海默病、精神分裂症和癫痫。

DESCRIPTION (provided by applicant): The formation and consolidation of memories requires bidirectional communication between the hippocampus and the neocortex via the entorhinal cortex (EC). EC layer V neurons are the main target of the processed output from the hippocampus and in turn project to cortical regions; these neurons are thus likely to play an important role in the formation and consolidation of memories. In addition, they have prominent apical dendrites that extend and branch in complex tufts in the EC superficial layers, where axons from different cortical areas are known to make synapses on EC layer II and III neurons. Our preliminary data show that these tufts carry many spines. The presence of these spines, combined with their proximity to axons emerging from cortical areas, suggests that these axons may form glutamatergic synaptic contacts on the distal dendrites of layer V neurons. The long-term goal of this research is to provide new insights with respect to the processing of memories by clarifying how entorhinal layer V neurons integrate the synaptic input they receive from the hippocampus with other inputs to generate their output to the neocortex. Two-photon Ca2+ imaging, glutamate uncaging and electrophysiological techniques will be employed to characterize different aspects of dendritic integration in layer V neurons of the rat entorhinal cortex. The project will focus on three specific aims: (1) to test the prediction that the distal apical dendrites of EC layer V neurons are activated by glutamatergic inputs whose features differ from those of the proximal hippocampal synapses; (2) to test the prediction that proximal and distal compartments can communicate through back-propagating action potentials (bAPs); (3) to test the prediction that the distal dendrites of EC layer V neurons can initiate dendritic spikes that alter the entorhinal output. The information acquired about the computational capabilities specific to the dendrites of these neurons will shed light on signal processing during normal and pathological neuronal activity. The resultant improvement in our understanding of how information is transmitted and stored in this critical area of the brain may eventually guide therapeutic strategies for disorders in which this area is particularly vulnerable, such as Alzheimer's disease, schizophrenia and epilepsy. PUBLIC HEALTH RELEVANCE: The formation and consolidation of memories requires bidirectional communication between the hippocampus and the neocortex via the entorhinal cortex. Two-photon Ca2+ imaging, glutamate uncaging and electrophysiological techniques will be used to characterize different aspects of dendritic integration in layer V neurons of the rat entorhinal cortex. The resultant improvement in our understanding of how information is transmitted and stored in this critical area of the brain may eventually lead to therapeutic strategies for disorders in which brain functions are compromised, such as epilepsy, Alzheimer's disease and schizophrenia.