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

项目总结： 海马尖波纹是在慢波睡眠或静止期间150-250赫兹的振荡。 大量海马神经元按顺序重复在探索过程中发生的活动模式 对环境的影响。清醒时的涟漪干扰会扰乱工作记忆。最近的工作有 研究表明，许多其他海马区外的大脑区域在纹波期间被特别激活，这一点 在波纹期间，海马区和新皮质网络的协调可能对学习和恢复至关重要。 然而，不同新皮质区域的细胞类型的准确识别和波纹期间激活的可靠性 是未知的。戈尔沙尼实验室最近开发了一种大型颅窗制剂，可以 美国将对所有脑区的神经元进行系统和无偏倚的钙成像 两侧额叶至枕叶皮质。在这里，我们建议植入由 Tolosa和Frank Labs作为大脑的一部分主动进入小鼠的海马体中植入大鼠 颅窗。这些柔性电极阵列将是这一目的的最佳选择，因为它们允许长时间使用 200天的本地磁场潜力记录；此外，因为它们是灵活的，所以它们可以被成形，以便它们 不要遮挡成像窗口。我们将首先通过访问Frank实验室来学习电极植入，地址为 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)，并将它们植入 具有大颅窗的Thy-1 GCAMP6s动物的海马体。在确保我们可以低表现之后 在跑步机上休息的头部固定动物的噪音电生理记录和钙成像，我们将 训练动物执行记忆提取任务。我们将确定不同皮质神经元的比例 在任务期间的波动期间激活的区域以及它们在几天内的可靠性激活。这一年R03 将允许我们收集显示这些实验的可行性的数据，我们将使用这些数据作为 协作性大脑计划拨款。

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.