Transformation of Neuronal Activity in the Entorhinal-hippocampal-neocortex Path

摘要 研究神经元回路的正确方法是什么？神经科学的主导策略是 来研究刺激、大脑信号和行为之间的关系。在这个框架中， 调查员处于特殊情况下。因为S/他既可以接触到大脑模式，也可以 大脑之外的信号，S/他可以建立它们之间的关联。然而，如果没有 此外，目前尚不清楚这些实验者观察到的相关性是否 实际上是被大脑利用的。本项目将采取另一种办法，即 研究上游回路中的神经元群体模式是如何被一个 存储器电路中的下游观察器电路/机构。使用这一战略，我们将 研究内嗅皮层(EC)中神经元活动在每个阶段是如何转化的- 齿状回(DG)-CA2/3-CA1-新皮质环，并将这种转换与 行为。这些项目将结合大规模电生理学、光遗传学和成像技术 表现得像啮齿类动物。项目1将检查内侧和侧向的不同贡献 内嗅皮层(MEC，LEC)与空间学习和对象学习有关，并将行为与EC-DG联系起来 θ-伽马振荡模式的传输。项目2将检查信息 在齿状回和EC-DG-CA3突触之间的传递。我们将首先量化 LFP和Spike-LFP偶联的变化以检测EC和DG颗粒细胞的贡献 DG苔藓细胞和CA3锥体细胞的放电模式的输入。然后我们将测试DG是否 颗粒和苔藓细胞重放与海马尖锐波纹或EC协调 经验后睡眠期间的细胞组装。最后，我们将测试光遗传 操纵齿状棘波会影响记忆，并诱导CA3网络的重新配置。 项目3考察了不同的神经元轨迹，如向前和向后 序列由CA3-CA1和CA1-顶叶皮质的靶回路差异读出 电路。最后，项目4将测试不同的海马区模式是否被翻译成 不同的新皮质功能图，以及这种图是否通过学习而修改。我们的 以读者为中心的方法将确定神经元模式是如何在内嗅觉- 海马体-内嗅环，提供了关键的见解生理机制。 学习记忆和相关疾病。

SUMMARY What is the right way to investigate neuronal circuits? The dominant strategy in neuroscience is to examine the relationships between stimuli, brain signals and behavior. In this framework, the investigator is in a privileged situation. Because s/he has access to both brain patterns and signals outside the brain, s/he can establish correlations between them. However, without further ‘grounding’, it remains unknown whether these experimenter-observed correlations are actually utilized by the brain. The present project will take an alternative approach by investigating how neuronal population patterns in an upstream circuit are ‘read out’ by a downstream observer circuit/mechanism in memory circuits. Using this strategy, we will investigate how neuronal activity is transformed at each stage in the entorhinal cortex (EC) – dentate gyrus (DG) – CA2/3 – CA1- neocortex loop, and relate such transformations to behavior. The projects will combine large-scale electrophysiology, optogenetics and imaging in behaving rodents. Project 1 will examine the distinct contributions of medial and lateral entorhinal cortex (MEC, LEC) to spatial versus object learning, and will link behavior to EC-DG transmission of theta-gamma oscillatory patterns. Project 2 will examine information transmission within the dentate gyrus and across EC-DG-CA3 synapses. We will first quantify changes in LFP and spike-LFP coupling to test the contributions of EC and DG granule cell input to the firing patterns of DG mossy and CA3 pyramidal cells. We will then test whether DG granule and mossy cell replay is coordinated with hippocampal sharp wave ripples or with EC cell assemblies during post-experience sleep. Finally, we will test whether optogenetic manipulation of dentate spikes affects memory and induces re-configuration of CA3 networks. Project 3 examines whether distinct neuronal trajectories, such as forward and reversed sequences, are read out differentially by target circuits in the CA3-CA1 and CA1-parietal cortical circuits. Finally, Project 4 will test whether different hippocampal patterns are translated to distinct neocortical functional maps and whether such maps are modified by learning. Our ‘reader-centric’ approach will establish how neuronal patterns are transformed in the entorhinal- hippocampal-entorhinal loop, providing critical insights into physiological mechanisms of learning and memory and relevant diseases.