Hippocampal Influences on Auditory Cortical Circuits as a Function of Brain State and Learning

项目摘要 海马体在情景记忆的形成中起着关键作用。当前占主导地位 假设记忆是在fl序列下跨分布的大脑皮层网络逐渐建立的 海马区的活动。然而，我们对fl中海马区的性质和范围的理解 大脑皮层回路仍然不完整。挑战的一部分是，任何亚阈值调制 大脑皮层神经元不能接触到细胞外记录，这一直是研究脑损伤的主要工具。 皮质-海马区的相互作用。我们建议将听觉皮质(AC)的全细胞记录与 从海马复合体(HC)到这一区域的投射的光遗传控制，以便量化 fl法观察HC-AC投射对单个皮层神经元膜电位动力学的影响 大脑状态和学习的功能。我们的目标是使用这种方法来识别直接接受 并研究它们的特性和体内相应突触的可塑性。 最后，我们的目标是在学习活动和学习期间使用HC-AC投影的光遗传扰动 以确定这些投射在记忆形成中的功能作用，并研究 它们参与合并进程的时机。大脑皮层亚阈值调制的量化 通过海马区输入的神经元可以灵敏地测量这些区域之间的功能耦合。 并使我们更接近于对它们的相互作用和它们在记忆形成中的作用的机械性理解。

Project Summary The hippocampus plays a critical role in the formation of episodic memories. The current predominant hypothesis is that memories are gradually established across distributed cortical networks under the influence of hippocampal activity. However, our understanding of the nature and extent of hippocampal influences on cortical circuits remains incomplete. Part of the challenge has been that any subthreshold modulation of cortical neurons is inaccessible to extracellular recordings, which have been the main tool for studying of cortico-hippocampal interactions. We propose to combine whole-cell recordings in auditory cortex (AC) with optogenetic control of the projections to this area from the hippocampal complex (HC), in order to quantify the influence of the HC-AC projections on the membrane potential dynamics of individual cortical neurons as a function of brain state and learning. We aim to use this approach to identify cortical neurons that receive direct hippocampal input, and characterize their properties and the plasticity of the corresponding synapses in vivo. Finally, we aim to use optogenetic perturbations of the HC-AC projections during learning events and hippocampal ripples to establish the functional role of these projections in memory formation, and to study the timing of their participation in the consolidation process. Quantifying the subthreshold modulation of cortical neurons by hippocampal inputs can provide sensitive measures of the functional coupling between these areas and bring us closer to a mechanistic understanding of their interactions and their role in memory formation.