Integrating flexible neural probes with a giant cranial window for combined electrophysiology and 2-photon calcium imaging of cortex-hippocampal interactions

项目概要： 海马尖波波纹是在慢波睡眠或不动期间的150-250 Hz振荡， 大量的海马神经元连续地重放探索过程中出现的活动模式 环境。在清醒状态下波动的中断会扰乱工作记忆。最近的工作已经 显示许多其他海马体外的大脑区域在涟漪期间被特别激活， 海马和新皮层网络在涟漪期间的协调对于学习和检索可能是关键的。 然而，不同新皮层区域细胞类型的精确识别和波纹期间激活的可靠性 不知道。Golshani实验室最近开发了一种大型颅窗准备， 我们对所有大脑区域的神经元进行系统和无偏见的钙成像， 双侧额叶到枕叶皮层在这里，我们建议植入柔性电极阵列开发的 Tolosa和Frank实验室作为BRAIN倡议的一部分，在小鼠海马中植入了大的 颅窗这些柔性电极阵列对于该目的将是最佳的，因为它们允许长时间的 局部场电位的记录>200天;此外，因为它们是灵活的，它们可以成形， 别挡住成像窗口。我们将首先通过访问弗兰克实验室来学习电极植入， 加州大学旧金山分校然后，我们将从Tolosa实验室获得柔性电极阵列（10个阵列），并将其植入到 Thy-1 GCAMP 6s动物的海马具有大颅窗。在确保我们可以表现得很低之后 噪声电生理记录和钙成像在头部固定的动物在跑步机上休息，我们将 训练动物执行记忆提取任务。我们将确定不同皮层神经元的比例， 在任务期间的涟漪期间激活的区域以及它们跨天激活的可靠性。今年R 03 将使我们能够收集数据，显示这些实验的可行性，我们将使用这些数据作为初步数据， 合作的大脑倡议赠款。

Project Summary: Hippocampal sharp-wave ripples are 150-250 Hz oscillations during slow-wave sleep or immobility during which large populations of hippocampal neurons sequentially replay activity patterns that occurred during exploration of the environment. Disruption of ripples during wakefulness disrupts working memory. Recent work has shown that many other extra-hippocampal brain regions are specifically activated during ripples, and this coordination of hippocampal and neocortical networks during ripples may be critical for learning and retrieval. Yet the precise identity of cell types across different neocortical regions and reliability of activation during ripples is not known. The Golshani Laboratory has recently developed a large cranial window preparation that allows us to perform systematic and unbiased calcium imaging of neurons across all brain regions extending from frontal to occipital cortex bilaterally. Here we propose to implant flexible electrode arrays developed by the Tolosa and Frank Labs as a part of the BRAIN initiative into the hippocampus in mouse implanted with the large cranial window. These flexible electrode arrays will be optimal for this purpose because they allow long lasting recordings of local field potential for >200 days; moreover, because they are flexible they can be shaped so they don't obscure the imaging window. We will first learn implantation of electrodes by visiting the Frank Lab at UCSF. We will then obtain flexible electrode arrays from the Tolosa Lab (10 arrays), and implant them into the hippocampus in Thy-1 GCAMP6s animals with the large cranial window. After assuring that we can perform low noise electrophysiological recordings and calcium imaging in head-fixed animals resting on the treadmill, we will train animals to perform a memory retrieval task. We will determine proportion of neurons in different cortical regions activated during ripples during the task and their reliability activation across days. This one year R03 will allow us to collect data showing feasibility of these experiments that we will use as preliminary data for a collaborative BRAIN initiative grant.